HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers...

41
HIV Monoclonal Antibodies III-A-206 DEC 98 Table 10: gp41 MAb ID Location WEAU Sequence Neutralizing Immunogen Species(Isotype) 626 5F3 gp41(526-543 BH10) gp41(15-33) AAGSTMGAASMTLTVQ- ARQ N HIV-1 infection human(IgG 1κ ) Donor: H. Katinger, Inst. Appl. Microbiol., Vienna, Austria References: [Buchacher et al.(1994)] NOTES: 5F3: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells [Buchacher et al.(1994)] 627 25C2 gp41(526-543 BH10) gp41(15-33) AAGSTMGAASMTLTVQ- ARQ N HIV-1 infection human(IgG 1κ ) Donor: H. Katinger, Inst. Appl. Microbiol., Vienna, Austria and Viral Testing Systems, Houston, TX References: [Buchacher et al.(1992), Buchacher et al.(1994), Sattentau et al.(1995)] NOTES: 25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher et al.(1994)] 25C2: Called IAM 41-25C2 – Binding domain overlaps sites that are critical for gp120-gp41 association gStM binding is enhanced by sCD4 – binding region defined as: gp41(21-38 BH10) [Sattentau et al.(1995)] 628 24G3 gp41(526-543 BH10) gp41(15-33) AAGSTMGAASMTLTVQ- ARQ N HIV-1 infection human(IgG 1κ ) Donor: H. Katinger, Inst. Appl. Microbiol., Vienna, Austria References: [Buchacher et al.(1992), Buchacher et al.(1994)] NOTES: 24G3: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells [Buchacher et al.(1994)] 629 1A1 gp41(526-543 BH10) gp41(15-33) AAGSTMGAASMTLTVQ- ARQ N HIV-1 infection human(IgG 1κ ) Donor: H. Katinger, Inst. Appl. Microbiol., Vienna, Austria References: [Buchacher et al.(1994)] NOTES: 1A1: Human MAb generated using EBV transformation of PBL from HIV-1+ volunteers [Buchacher et al.(1994)] 630 α(566-586) gp41(566-586 BRU) gp41(51-71) AQQHLLQLTVWGIKQLQ- ARIL HIV-1 infection human Donor: H. Katinger, Inst. Appl. Microbiol., Vienna, Austria References: [Poumbourios et al.(1992)]

Transcript of HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers...

Page 1: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-206

DE

C98

Table10: g

p41

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

6265F

3gp41(526-543

BH

10)gp41(15-33)

AA

GS

TM

GA

AS

MT

LTV

Q-

AR

QN

HIV

-1infection

human(IgG1

κ )

Donor:

H.K

atinger,Inst.A

ppl.M

icrobiol.,Vienna,A

ustriaR

eferences:[Buchacher

etal.(1994)]N

OT

ES

:•

5F3:

Hum

anM

Ab

generatedby

electrofusionof

PB

Lfrom

HIV

-1+volunteers

with

CB

-F7

cells[B

uchacheretal.(1994)]

62725C

2gp41(526-543

BH

10)gp41(15-33)

AA

GS

TM

GA

AS

MT

LTV

Q-

AR

QN

HIV

-1infection

human(IgG1

κ )

Donor:

H.K

atinger,Inst.A

ppl.M

icrobiol.,Vienna,A

ustriaand

ViralTesting

System

s,Houston,T

XR

eferences:[Buchacher

etal.(1992),Buchacher

etal.(1994),Sattentau

etal.(1995)]N

OT

ES

:•

25C2:

Hum

anM

Ab

generatedby

electrofusionofP

BL

fromH

IV-1+

volunteersw

ithC

B-F

7cells

–binds

oligomeric

andm

onomeric

gp41,andgp160

[Buchacher

etal.(1994)]•

25C2:

Called

IAM

41-25C2

–B

indingdom

ainoverlaps

sitesthat

arecriticalfor

gp120-gp41association

gStM

–binding

isenhanced

bysC

D4

–binding

regiondefined

as:gp41(21-38

BH

10)[S

attentauetal.(1995)]

62824G

3gp41(526-543

BH

10)gp41(15-33)

AA

GS

TM

GA

AS

MT

LTV

Q-

AR

QN

HIV

-1infection

human(IgG1

κ )

Donor:

H.K

atinger,Inst.A

ppl.M

icrobiol.,Vienna,A

ustriaR

eferences:[Buchacher

etal.(1992),Buchacher

etal.(1994)]N

OT

ES

:•

24G3:

Hum

anM

Ab

generatedby

electrofusionof

PB

Lfrom

HIV

-1+volunteers

with

CB

-F7

cells[B

uchacheretal.(1994)]

6291A

1gp41(526-543

BH

10)gp41(15-33)

AA

GS

TM

GA

AS

MT

LTV

Q-

AR

QN

HIV

-1infection

human(IgG1

κ )

Donor:

H.K

atinger,Inst.A

ppl.M

icrobiol.,Vienna,A

ustriaR

eferences:[Buchacher

etal.(1994)]N

OT

ES

:•

1A1:

Hum

anM

Ab

generatedusing

EB

Vtransform

ationofP

BL

fromH

IV-1+

volunteers[B

uchacheretal.(1994)]

630α

(566-586)gp41(566-586

BR

U)

gp41(51-71)A

QQ

HLLQ

LTV

WG

IKQ

LQ-

AR

ILH

IV-1

infectionhum

an

Donor:

H.K

atinger,Inst.A

ppl.M

icrobiol.,Vienna,A

ustriaR

eferences:[Poum

bouriosetal.(1992)]

Page 2: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-207

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

631P

C5009

gp41(577-596B

RU

)gp41(62-81)

GIK

QLQ

AR

ILAVE

RY

LK-

DQ

Qrgp160

murine

Donor:

H.K

atinger,Inst.A

ppl.M

icrobiol.,Vienna,A

ustriaR

eferences:[Poum

bouriosetal.(1992)]

NO

TE

S:

•P

C5009:

Recognized

onlym

onomeric

gp41[P

oumbourios

etal.(1992)]

632polyclonalα

(577-596)gp41(577-596

BR

U)

gp41(62-81)G

IKQ

LQA

RILAV

ER

YLK

-D

QQ

HIV

-1infection

human

plasma

Donor:

H.K

atinger,Inst.A

ppl.M

icrobiol.,Vienna,A

ustriaR

eferences:[Poum

bouriosetal.(1992)]

NO

TE

S:

•α

(577-596):A

ffinitypurified

fromH

IV-1+

plasma

–preferentially

bindoligom

er[P

oumbourios

etal.(1992)]

633polyclonal

gp41(583-604)gp41(69-89)

RILAV

ER

YLK

DQ

QLLG

I-W

GC

SN

desialylatedH

IV-1

gp160rabbit

sera

Donor:

H.K

atinger,Inst.A

ppl.M

icrobiol.,Vienna,A

ustriaR

eferences:[Benjouad

etal.(1993)]N

OT

ES

:•

MA

bsraised

againstdesialylated

HIV

-1gp160

cross-reactw

ithH

IV-2

gp140due

toim

munodom

inantconserved

epitopein

gp41[B

enjouadetal.(1993)]

634polyclonal

gp41(584-602)gp41(70-87)

ILAVE

RY

LKD

QQ

LLGIW

GN

HIV

-1infection

human

seraD

onor:H

.Katinger,Inst.

Appl.

Microbiol.,V

ienna,Austria

References:[P

etrovetal.(1990)]

NO

TE

S:

•Im

munodom

inantandbroadly

reactivepeptide

[Petrov

etal.(1990)]

635V

10-9gp41(586-620

IIIB)

gp41(70-103)ILAV

ER

YLK

DQ

QLLG

IW-

GC

SG

KLIC

TTAV

PW

NA

SN

HIV

-1infection

human(IgG1

κ )

Donor:

H.K

atinger,Inst.A

ppl.M

icrobiol.,Vienna,A

ustriaR

eferences:[Robinson

Jr.etal.(1990a),R

obinsonJr.

etal.(1990b)]N

OT

ES

:•

V10-9:

Antibody

dependentenhancement(A

DE

)ofHIV

-1IIIB

infectivity,synergisticallyenhanced

byM

Ab

120-16[R

obinsonJr.

etal.(1990a)]•

V10-9:

Peptide

586-620blocks

complem

entmediated

AD

E[R

obinsonJr.

etal.(1990b)]

Page 3: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-208

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

63686

gp41(586-620IIIB

)gp41(69-103)

RILAV

ER

YLK

DQ

QLLG

I-W

GC

SG

KLIC

TTAV

PW

NA

SN

HIV

-1infection

human(IgG1

κ )

Donor:

Evan

Hersh

andYoh-IchiM

atsumoto

References:[S

uganoet

al.(1988),R

obinsonJr.

etal.(1990a),

Robinson

Jr.et

al.(1990b),P

incuset

al.(1991),M

oranetal.(1993),W

isnewskietal.(1996),M

itchelletal.(1998)]N

OT

ES

:•

86:A

lsocalled

No.

86•

86:R

eactsw

ithgp41

andalso

reactedw

eaklyw

ithgp120

[Sugano

etal.(1988)]•

86:A

ntibodydependentenhancem

ent(AD

E)

ofHIV

-1IIIB

infectivityin

thepresence

ofcomplem

ent[Robinson

Jr.etal.(1990a)]

•86:

Peptide

586-620blocks

complem

entmediated

AD

E[R

obinsonJr.

etal.(1990b)]•

86:P

oorimm

unotoxinactivity

when

coupledto

RA

C–

peptidebinding

statedto

beaa

579-603[P

incusetal.(1991)]

•86:

Heavy

(VH

I)and

light(Vκ I)

chainsequenced

–enhancing

activity–

similar

germline

sequenceto

MA

bS

1-1,butvery

differentactivity[M

oranetal.(1993)]

•86:

86is

VH

1–

V-region

heavychain

usagew

asexam

inedand

abias

ofenhancedV

H1

andVH

4,andreduced

VH3,

was

notedam

ongH

IVinfected

individuals[W

isnewskietal.(1996)]

•86:

Mutations

inB

H10

gp160,W

596Yand

T605A

,as

wellas

deletionsof

605-609(T

TAVP

)and

597-609(G

CS

-G

KLIC

TTAV

P),abrogate

bindingofenhancing

MA

bs86,240D

,50-69,and246-D

–5/6

enhancingM

Abs

identifiedto

datebind

tothe

imm

unodominantregion

579-613[M

itchelletal.(1998)]•

86:N

IHA

IDS

Research

andR

eferenceR

eagentProgram

:380

637polyclonal

gp41(74-94?)

gp41E

RY

LKD

QLLG

IWG

CS

GK

-LIC

HIV

-1infection

human

sera

Donor:

Evan

Hersh

andYoh-IchiM

atsumoto

References:[S

hafferman

etal.(1989)]N

OT

ES

:•

Imm

unogenicdom

ainusefulfor

diagnostics[S

hafferman

etal.(1989)]

63841-6

gp41(598-609)gp41(88-94)

CS

GK

LICpeptide

LGLIW

GC

-S

GK

LIC(aa

598-609)

murine(IgG

2b )

Donor:

Evan

Hersh

andYoh-IchiM

atsumoto

References:[O

ldstoneetal.(1991)]

NO

TE

S:

•41-6:

Poor

cross-reactivityw

ithH

IV-2

peptideC

AF

RQ

VC

–slightly

more

reactivew

ithLG

LIWG

CS

GK

LICand

HIV

-2form

NS

WG

CA

FR

QV

C–

disulfidebond

between

cysteinesrequired

[Oldstone

etal.(1991)]

Page 4: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-209

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

6394

gp41(598-609)gp41(88-94)

CS

GK

LICpeptide

LGLIW

GC

-S

GK

LIC(aa

598-609)

murine(IgG

2b )

Donor:

Evan

Hersh

andYoh-IchiM

atsumoto

References:[O

ldstoneetal.(1991)]

NO

TE

S:

•4:

There

isanother

MA

bw

iththis

IDthatreacts

with

integrase[O

ldstoneetal.(1991),B

izub-Bender

etal.(1994)]•

4:P

oorcross-reactivity

with

HIV

-2peptide

CA

FR

QV

C–

slightlym

orereactive

with

longerH

IV-2

peptideN

SW

G-

CA

FR

QV

C[O

ldstoneetal.(1991)]

64075

gp41(598-609)gp41(88-94)

CS

GK

LICpeptide

LGLIW

GC

-S

GK

LIC(aa

598-609)

rat(IgG)

Donor:

Evan

Hersh

andYoh-IchiM

atsumoto

References:[O

ldstoneetal.(1991)]

NO

TE

S:

•75:

Poor

cross-reactivityw

ithH

IV-2

peptideC

AF

RQ

VC

–m

orereactive

with

longerH

IV-2

peptideN

SW

G-

CA

FR

QV

C[O

ldstoneetal.(1991)]

64168.1

gp41(598-609)gp41(88-94)

CS

GK

LICpeptide

LGLIW

GC

-S

GK

LIC(aa

598-609)

murine(IgM

)

Donor:

Evan

Hersh

andYoh-IchiM

atsumoto

References:[O

ldstoneetal.(1991)]

NO

TE

S:

•68.1:

Cross-reactive

with

HIV

-2peptide

CA

FR

QV

C–

more

reactivew

ithlongerH

IV-1

peptideLG

LIWG

CS

GK

LICand

HIV

-2peptide

NS

WG

CA

FR

QV

C[O

ldstoneetal.(1991)]

64268.11

gp41(598-609)gp41(88-94)

CS

GK

LICpeptide

LGLIW

GC

-S

GK

LIC(aa

598-609)

murine(IgM

)

Donor:

Evan

Hersh

andYoh-IchiM

atsumoto

References:[O

ldstoneetal.(1991)]

NO

TE

S:

•68.11:

Cross-reactive

with

HIV

-2peptide

CA

FR

QV

C–

more

reactivew

ithlongerH

IV-1

peptideLG

LIWG

CS

GK

LICand

HIV

-2peptide

NS

WG

CA

FR

QV

C[O

ldstoneetal.(1991)]

Page 5: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-210

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

643115.8

gp41(598-609)gp41(82-94)

LGLIW

GC

SG

KLIC

peptideLG

LIWG

C-

SG

KLIC

(aa598-

609)

murine(IgM

)

Donor:

Evan

Hersh

andYoh-IchiM

atsumoto

References:[O

ldstoneetal.(1991)]

NO

TE

S:

•115.8:

Poor

reactivityw

ithC

SG

KLIC

–reacts

well

with

longerH

IV-2

peptideN

SW

GC

AF

RQ

VC

asw

ellas

CA

FR

QV

C–

disulfidebond

between

cysteinesrequired

[Oldstone

etal.(1991)]

644M

-22gp41(598-609)

gp41(83-94)LG

IWG

CS

GK

LICH

IV-1

gp41peptide

(aa598-609)

murine(IgG

2b )

Donor:

?R

eferences:[Yam

adaetal.(1991)]

NO

TE

S:

•M

-22:S

trongestreactionof12

anti-HIV

-1gp41

MA

bsto

acellular43-kD

aprotein

foundin

ratandhum

anastrocytes

[Yam

adaetal.(1991)]

645M

-24gp41(598-609)

gp41(83-94)LG

IWG

CS

GK

LICH

IV-1

gp41peptide

(aa598-609)

murine(IgG

1 )

Donor:

?R

eferences:[Yam

adaetal.(1991)]

NO

TE

S:

•M

-24:S

tronglyreacted

with

acellular

43-kDa

proteinfound

inrat

andhum

anastrocytes

asw

ellas

with

gp41[Y

amada

etal.(1991)]

646M

-28gp41(598-609)

gp41(83-94)LG

IWG

CS

GK

LICH

IV-1

gp41peptide

(aa598-609)

murine(IgG

1 )

Donor:

?R

eferences:[Yam

adaetal.(1991)]

NO

TE

S:

•M

-28:S

tronglyreacted

with

acellular

43-kDa

proteinfound

inrat

andhum

anastrocytes

asw

ellas

with

gp41[Y

amada

etal.(1991)]

647M

-2gp41(598-609)

gp41(83-94)LG

IWG

CS

GK

LICH

IV-1

gp41peptide

(aa598-609)

murine(IgG

2b )

Donor:

?R

eferences:[Yam

adaetal.(1991)]

NO

TE

S:

•M

-2:S

tronglyreacted

with

acellular43-kD

aprotein

foundin

ratandhum

anastrocytes

asw

ellasw

ithgp41

[Yam

adaetal.(1991)]

Page 6: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-211

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

648M

-11gp41(598-609)

gp41(83-94)LG

IWG

CS

GK

LICH

IV-1

gp41peptide

(aa598-609)

murine(IgG

1 )

Donor:

?R

eferences:[Yam

adaetal.(1991)]

NO

TE

S:

•M

-11:S

tronglyreacted

with

acellular

43-kDa

proteinfound

inrat

andhum

anastrocytes

asw

ellas

with

gp41[Y

amada

etal.(1991)]

649M

-13gp41(598-609)

gp41(83-94)LG

IWG

CS

GK

LICH

IV-1

gp41peptide

(aa598-609)

murine(IgG

2b )

Donor:

?R

eferences:[Yam

adaetal.(1991)]

NO

TE

S:

•M

-13:R

eactedw

itha

cellular43-kD

aprotein

foundin

ratand

human

astrocytesas

well

asw

ithgp41

[Yam

adaetal.(1991)]

650M

-25gp41(598-609)

gp41(83-94)LG

IWG

CS

GK

LICH

IV-1

gp41peptide

(aa598-609)

murine(IgG

1 )

Donor:

?R

eferences:[Yam

adaetal.(1991)]

NO

TE

S:

•M

-25:R

eactedw

itha

cellular43-kD

aprotein

foundin

ratand

human

astrocytesas

well

asw

ithgp41

[Yam

adaetal.(1991)]

651M

-1gp41(598-609)

gp41(83-94)LG

IWG

CS

GK

LICH

IV-1

gp41peptide

(aa598-609)

murine(IgG

1or2b )

Donor:

?R

eferences:[Yam

adaetal.(1991)]

NO

TE

S:

•M

-1:U

nlikeM

-22,didnotreactto

43-kDa

proteinfound

inratand

human

astrocytes[Y

amada

etal.(1991)]

652M

-4gp41(598-609)

gp41(83-94)LG

IWG

CS

GK

LICH

IV-1

gp41peptide

(aa598-609)

murine(IgG

2b )

Donor:

?R

eferences:[Yam

adaetal.(1991)]

NO

TE

S:

•M

-4:U

nlikeM

-22,didnotreactto

43-kDa

proteinfound

inratand

human

astrocytes[Y

amada

etal.(1991)]

Page 7: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-212

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

653M

-6gp41(598-609)

gp41(83-94)LG

IWG

CS

GK

LICH

IV-1

gp41peptide

(aa598-609)

murine(IgG

2b )

Donor:

?R

eferences:[Yam

adaetal.(1991)]

NO

TE

S:

•M

-6:U

nlikeM

-22,didnotreactto

43-kDa

proteinfound

inratand

human

astrocytes[Y

amada

etal.(1991)]

654M

-29gp41(598-609)

gp41(83-94)LG

IWG

CS

GK

LICH

IV-1

gp41peptide

(aa598-609)

murine(IgG

1 )

Donor:

?R

eferences:[Yam

adaetal.(1991)]

NO

TE

S:

•M

-29:U

nlikeM

-22,didnotreactto

43-kDa

proteinfound

inratand

human

astrocytes[Y

amada

etal.(1991)]

655M

-36gp41(598-609)

gp41(83-94)LG

IWG

CS

GK

LICH

IV-1

gp41peptide

(aa598-609)

murine(IgG

1 )

Donor:

?R

eferences:[Yam

adaetal.(1991)]

NO

TE

S:

•M

-36:U

nlikeM

-22,didnotreactto

43-kDa

proteinfound

inratand

human

astrocytes[Y

amada

etal.(1991)]

6561B

8.envgp41(594-605

HX

B2)

gp41(84-94)G

IWG

CS

GK

LICN

HIV

-1infection

human(IgG

2λ )

Donor:

?R

eferences:[Banapour

etal.(1987)]N

OT

ES

:•

1B8.env:

Highly

conservedepitope

recognizedby

them

ajorityofH

IV-1

infectedpeople

[Banapour

etal.(1987)]

657polyclonalα

(598-609)gp41(598-609)

gp41(84-91)G

IWG

CS

GK

HIV

-1infection

human

Donor:

?R

eferences:[Poum

bouriosetal.(1992)]

NO

TE

S:

•α

(598-609):A

ffinitypurified

fromH

IV-1+

plasma

–im

munodom

inantregion,bindsoligom

erandm

onomer[P

oum-

bouriosetal.(1992)]

Page 8: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-213

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

658clone

3gp41

gp41(87-96)G

CS

GK

LICT

TL

HIV

-1infection

human(IgG

1 )D

onor:?

References:[C

otropiaetal.(1992),C

otropiaetal.(1996)]

NO

TE

S:

•clone

3:C

orebinding

domain

gcsgkLIC–

lackofserologicalactivity

tothis

regioncorrelates

with

rapidprogression

ininfants

([Broliden

etal.(1989)])[C

otropiaetal.(1992)]

•clone

3:Inhibits

replicationofthree

diverseH

IV-1

laboratorystrains,as

wellas

anA

ZT-resistantisolate

[Cotropia

etal.(1996)]

659polyclonal

gp41(601-616)gp41(84-99)

GIW

GC

SG

KLIC

TTAV

PN

HIV

-1infection

human

seraD

onor:?

References:[P

etrovetal.(1990)]

NO

TE

S:

•Im

munodom

inantandbroadly

reactivepeptide

[Petrov

etal.(1990)]

66041-7

gp41(605-611)gp41(88-94)

CS

GK

LICN

HIV

-1infection

human(IgG

1κ )

Donor:

?R

eferences:[Bugge

etal.(1990)]N

OT

ES

:•

41-7:S

erafrom

6/6H

IV-1

positive,but

noH

IV-2

positive,individuals

interferedw

ith41-7

binding[B

uggeetal.(1990)]

6612A

2/26gp41(584-606

BR

U)

gp41(69-91)R

ILAVE

RY

LKD

QQ

LLGI-

WG

CS

GK

viralgp41m

urine(IgG)

Donor:

?R

eferences:[Poum

bouriosetal.(1992),P

oumbourios

etal.(1995)]N

OT

ES

:•

2A2/26:

Imm

unodominantregion,binds

botholigom

erand

monom

er[P

oumbourios

etal.(1992)]•

2A2/26:

∆550-561

(∆LLR

AIE

AQ

QH

LL),a

regionim

portantfor

oligomer

formation

diminishes

binding,∆

(550-561+

571-581)abrogates

binding[P

oumbourios

etal.(1995)]

Page 9: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-214

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

66298-43

gp41(579-604H

XB

2)gp41(69-94)

RILAV

ER

YLK

DQ

QLLG

I-W

GC

SG

KLIC

NH

IV-1

infectionhum

an(IgG2κ )

Donor:

?R

eferences:[Pinter

etal.(1989),Gorny

etal.(1989),Tyleretal.(1990),X

uetal.(1991)]

NO

TE

S:

•98-43:

Reacts

equallyw

ellwith

oligomer

andm

onomer

[Pinter

etal.(1989)]•

98-43:P

oorA

DC

C(in

contrasttoM

Ab

120-16,gp41(644-663))[Tyler

etal.(1990)]•

98-43:579-604

bindsin

theim

munodom

inantregion[X

uetal.(1991)]

•98-43:

NIH

AID

SR

esearchand

Reference

ReagentP

rogram:

1241

663181-D

gp41(591-597H

XB

2)gp41(81-87)

QLLG

IWG

NH

IV-1

infectionhum

an(IgG2κ )

Donor:

?R

eferences:[Xu

etal.(1991),Robinson

Jr.etal.(1991),E

ddlestonetal.(1993),F

orthaletal.(1995),Fontenotetal.(1995)]

NO

TE

S:

•181-D

:Fine

mapping

indicatescore

isLLG

IW[X

uetal.(1991)]

•181-D

:No

enhancingor

neutralizationactivity

[Robinson

Jr.etal.(1991)]

•181-D

:Called

SZ

-181.D[E

ddlestonetal.(1993)]

•181-D

:No

neutralizing,noA

DC

C,and

noviralenhancing

activity[F

orthaletal.(1995)]

664240-D

gp41(592-600H

XB

2)gp41(82-90)

LLGIW

GC

SG

NH

IV-1

infectionhum

an(IgG1κ )

Donor:

?R

eferences:[Xu

etal.(1991),Robinson

Jr.etal.(1991),S

pearetal.(1993),B

inleyetal.(1996),W

isnewskietal.(1995),

Wisnew

skietal.(1996),Mitchelletal.(1998)]

NO

TE

S:

•240-D

:Fine

mapping

indicatescore

isIW

G[X

uetal.(1991)]

•240-D

:No

neutralizingactivity,som

eenhancing

activity[R

obinsonJr.

etal.(1991)]•

240-D:D

idnotm

ediatedeposition

ofcomplem

entcomponentC

3on

HIV

infectedcells

[Spear

etal.(1993)]•

240-D:B

indsto

alinear

epitopelocated

inthe

Cluster

Iregion–

bindingof50-69

and240-D

inhibitedby

Fabs

A1,

A4,M

8B,M

26B,M

12Band

T2

[Binley

etal.(1996)]•

240-D:

Called

F240:

F240

inVH

3–

V-region

heavychain

usagew

asexam

inedand

abias

ofenhanced

VH

1and

VH

4,andreduced

VH3,w

asnoted

among

HIV

infectedindividuals

[Wisnew

skietal.(1996)]•

240-D:

Mutations

inB

H10

gp160,W

596Yand

T605A

,as

well

asdeletions

of605-609

(TTAV

P)

and597-609

(GC

SG

KLIC

TTAV

P),

abrogatebinding

ofenhancing

MA

bs86,

240D,

50-69,and

246-D–

5/6enhancing

MA

bsidentified

todate

bindto

theim

munodom

inantregion579-613

[Mitchelletal.(1998)]

•240-D

:NIH

AID

SR

esearchand

Reference

ReagentP

rogram:

1242

Page 10: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-215

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

665D

61gp41(592-608

HX

B2)

gp41(82-98)LLG

IWG

CS

GK

LICT

TA

Vdim

ericE

nvm

urineD

onor:?

References:[E

arletal.(1994),Richardson

Jretal.(1996),W

eissenhornetal.(1996),E

arletal.(1997)]N

OT

ES

:•

D61:

Lineargp41epitope

inthe

clusterIregion–

human

serablocked

bindingin

oligomeric

ELIS

Aassay

toa

similar

extentforgp41

MA

bsD

20,D43,D

61,andT

4[R

ichardsonJr

etal.(1996)]•

D61:

Does

notprecipitate

gp41(21-166),but

dueto

astructuraldifference

inthe

disulfidebonding

regionnear

thetw

ocysteines

–the

authorspropose

thatthisregion

may

changeconform

ationduring

theactivation

ofthem

embrane

fusionstate

oftheH

IV-1

glycoprotein[W

eissenhornetal.(1996)]

•D

61:B

indingm

apsto

region597-613:

WG

CS

GK

LICT

TAVP

WN

A–

imm

unodominantregion

containingtw

oC

ysresidues

–this

antibody,alongw

ithhum

anM

Ab

246-D,can

beblocked

byany

ofagroup

of8conform

ationalMA

bs(M

10,D41,D

54,T4,T

6,T9,T

10and

T35)

–m

embers

ofthiscom

petitiongroup

areblocked

bysera

fromH

IV-1+

individuals[E

arletal.(1997)]

666D

49gp41(597-613)

gp41(82-98)LLG

IWG

CS

GK

LICT

TA

Vdim

ericE

nvm

urineD

onor:?

References:[E

arletal.(1994),Earletal.(1997)]

NO

TE

S:

•D

49:B

indingm

apsto

region597-613:

WG

CS

GK

LICT

TAVP

WN

A–

imm

unodominantregion

containingtw

oC

ysresidues

[Earletal.(1997)]

667T

32gp41(597-613)

gp41(82-98)LLG

IWG

CS

GK

LICT

TA

Vtetram

ericE

nvm

urineD

onor:?

References:[E

arletal.(1994),Earletal.(1997)]

NO

TE

S:

•T

32:B

indingm

apsto

region597-613:

WG

CS

GK

LICT

TAVP

WN

A–

imm

unodominantregion

containingtw

oC

ysresidues

[Earletal.(1997)]

668T

34gp41(597-613)

gp41(82-98)LLG

IWG

CS

GK

LICT

TA

Vtetram

ericE

nvm

urineD

onor:?

References:[E

arletal.(1994),Earletal.(1997)]

NO

TE

S:

•T

34:B

indingm

apsto

region597-613:

WG

CS

GK

LICT

TAVP

WN

A–

imm

unodominantregion

containingtw

oC

ysresidues

[Earletal.(1997)]

Page 11: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-216

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

669246-D

gp41(579-604H

XB

2)gp41(80-87)

QQ

LLGIW

GN

HIV

-1infection

human(IgG

1κ )

Donor:

Susan

Zolla-P

azner,NY

UM

edC

enter,NY,N

YR

eferences:[Xu

etal.(1991),Robinson

Jr.etal.(1991),S

pearetal.(1993),E

ddlestonetal.(1993),F

orthaletal.(1995),M

ancaetal.(1995),S

aarloosetal.(1995),E

arletal.(1997)]N

OT

ES

:•

246-D:F

inem

appingindicates

coreis

LLGI[X

uetal.(1991)]

•246-D

:Did

notmediate

depositionofcom

plementcom

ponentC3

onH

IVinfected

cellsunless

cellsw

erepre-incubated

with

sCD

4[S

pearetal.(1993)]

•246-D

:No

neutralizingactivity,som

eenhancing

activity[R

obinsonJr.

etal.(1991)]•

246-D:C

alledS

Z-246.D

[Eddleston

etal.(1993)]•

246-D:N

oneutralizing

activity,bothA

DC

Cand

viralenhancingactivity

[Forthaletal.(1995)]

•246-D

:Virions

complexed

togp41

Ab

facilitatepresentation

ofp66R

Tepitopes

toT

hcells

[Manca

etal.(1995)]•

246-D:

Ab-m

ediatedactivation

ofcom

plement

onH

IV+

cellsis

higherthan

Ab

independentactivation

–w

hathas

beenterm

ed“A

bindependent”

infact

resultsin

partfrom

IgMin

normalhum

anserum

thatis

HIV

-cross-reactive[S

aarloosetal.(1995)]

•246-D

:M

utationsin

BH

10gp160,

W596Y

andT

605A,

asw

ellas

deletionsof

605-609(T

TAVP

)and

597-609(G

CS

GK

LICT

TAVP

),abrogate

bindingof

enhancingM

Abs

86,240D

,50-69,

and246-D

–5/6

enhancingM

Abs

identifiedto

datebind

tothe

imm

unodominantregion

579-613[M

itchelletal.(1998)]•

246-D:

This

antibody,along

with

murine

MA

bD

61,can

beblocked

byany

ofa

groupof

8conform

ationalMA

bs(M

10,D41,D

54,T4,T

6,T9,T

10and

T35)

[Earletal.(1997)]

•246-D

:NIH

AID

SR

esearchand

Reference

ReagentP

rogram:

1245

6702F

11gp41(H

XB

2)gp41(79-90)

DQ

QLLG

IWG

CS

GN

HIV

-1infection

human(IgG

1 )D

onor:?

References:[E

atonetal.(1994)]

NO

TE

S:

•2F

11:E

nhancesinfectivity

evenin

theabsence

ofcomplem

ent–does

notmediate

AD

CC

orneutralize

virus[E

atonetal.(1994)]

6711H

5gp41(579-613

BH

10)gp41(68-102)

AR

ILAVE

RY

LKD

QQ

LLG-

IWG

CS

GK

LICT

TAVP

WN

AN

HIV

-1infection

human(IgG1

κ )

Donor:

?R

eferences:[Buchacher

etal.(1992),Buchacher

etal.(1994)]N

OT

ES

:•

1H5:

Generated

byelectrofusion

ofPB

Lfrom

HIV

-1positive

volunteersw

ithC

B-F

7cells

[Buchacher

etal.(1994)]

Page 12: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-217

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

6721F

11gp41(579-613

BH

10)gp41(68-102)

AR

ILAVE

RY

LKD

QQ

LLG-

IWG

CS

GK

LICT

TAVP

WN

AN

HIV

-1infection

human(IgG1

κ )

Donor:

H.K

atinger,Inst.A

ppl.M

icrobiol.,Vienna,A

ustriaR

eferences:[Buchacher

etal.(1992),Buchacher

etal.(1994)]N

OT

ES

:•

1F11:

Generated

byelectrofusion

ofPB

Lfrom

HIV

-1positive

volunteersw

ithC

B-F

7cells

[Buchacher

etal.(1994)]

6734D

4gp41(579-613

BH

10)gp41(68-102)

AR

ILAVE

RY

LKD

QQ

LLG-

IWG

CS

GK

LICT

TAVP

WN

AN

HIV

-1infection

human(IgG1

λ )

Donor:

H.K

atinger,Inst.A

ppl.M

icrobiol.,Vienna,A

ustriaand

ViralTesting

System

s,Houston,T

XR

eferences:[Buchacher

etal.(1992),Buchacher

etal.(1994),Chen

etal.(1994b),Sattentau

etal.(1995)]N

OT

ES

:•

4D4:

Generated

byelectrofusion

ofPB

Lfrom

HIV

-1positive

volunteersw

ithC

B-F

7cells

[Buchacher

etal.(1994)]

6743D

9gp41(579-613

BH

10)gp41(68-102)

AR

ILAVE

RY

LKD

QQ

LLG-

IWG

CS

GK

LICT

TAVP

WN

AN

HIV

-1infection

human(IgG1

κ )

Donor:

H.K

atinger,Inst.A

ppl.M

icrobiol.,Vienna,A

ustriaR

eferences:[Buchacher

etal.(1992),Buchacher

etal.(1994)]N

OT

ES

:•

3D9:

Generated

byelectrofusion

ofPB

Lfrom

HIV

-1positive

volunteersw

ithC

B-F

7cells

[Buchacher

etal.(1994)]

6754G

2gp41(579-613

BH

10)gp41(68-102)

AR

ILAVE

RY

LKD

QQ

LLG-

IWG

CS

GK

LICT

TAVP

WN

AN

HIV

-1infection

human(IgG1

κ )

Donor:

H.K

atinger,Inst.A

ppl.M

icrobiol.,Vienna,A

ustriaR

eferences:[Buchacher

etal.(1992),Buchacher

etal.(1994)]N

OT

ES

:•

4G2:

Generated

byelectrofusion

ofPB

Lfrom

HIV

-1positive

volunteersw

ithC

B-F

7cells

[Buchacher

etal.(1994)]

6764B

3gp41(579-613

BH

10)gp41(68-102)

AR

ILAVE

RY

LKD

QQ

LLG-

IWG

CS

GK

LICT

TAVP

WN

AN

HIV

-1infection

human(IgG1

λ )

Donor:

H.K

atinger,Inst.A

ppl.M

icrobiol.,Vienna,A

ustriaR

eferences:[Buchacher

etal.(1992),Buchacher

etal.(1994),Chen

etal.(1994b)]N

OT

ES

:•

4B3:

Generated

byelectrofusion

ofPB

Lfrom

HIV

-1positive

volunteersw

ithC

B-F

7cells

[Buchacher

etal.(1994)]

Page 13: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-218

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

67750-69

gp41(579-603B

H10)

gp41(69-93)R

ILAVE

RY

LKD

QQ

LLGI-

WG

CS

GK

LIN

HIV

-1infection

human(IgG2

κ )

Donor:

Susan

Zolla-P

azner,NY

U,N

YR

eferences:[Tilletal.(1989),P

interetal.(1989),Gorny

etal.(1989),Xu

etal.(1991),Robinson

Jr.etal.(1991),S

attentau&

Moore(1991),

Eddleston

etal.(1993),

Spear

etal.(1993),

Laaletal.(1994),

Chen

etal.(1995),

Sattentau

etal.(1995),

Manca

etal.(1995),

McD

ougalet

al.(1996),P

oignardet

al.(1996a),B

inleyet

al.(1996),K

lasse&

Sattentau(1996),

Stam

atatosetal.(1997),B

ootsetal.(1997),M

itchelletal.(1998)]N

OT

ES

:•

50-69:C

ombined

with

deglycosylatedA

chainofricin

istoxic

tolines

ofHIV

-infectedT

cells(H

9)and

monocytes

(U937)

[Tilletal.(1989)]

•50-69:

Reacts

preferentiallyw

ithgp160

oligomer,com

paredto

gp41m

onomer

[Pinter

etal.(1989)]•

50-69:K

illsH

IV-infected

cellsw

hencoupled

todeglycosylated

ricinA

chain[G

ornyetal.(1989)]

•50-69:

The

epitopeis

affectedby

theconform

ationconferred

bythe

two

cysteinesatam

inoacids

598and

604[X

uetal.(1991)]

•50-69:

Enhances

HIV

-1infection

invitro

–synergizes

with

huMA

b120-16

invitro

toenhance

HIV

-1infection

tolevelapproaching

thatfoundin

polyclonalanti-HIV

serum[R

obinsonJr.

etal.(1991)]•

50-69:Tw

ofold

increasein

bindingto

gp120in

thepresence

ofboundsC

D4

[Sattentau

&M

oore(1991)]•

50-69:C

alledS

Z-50.69

–binds

toan

epitopew

ithinaa

579-613[E

ddlestonetal.(1993)]

•50-69:

Did

notmediate

depositionofcom

plementcom

ponentC3

onH

IVinfected

cellsunless

cellsw

erepre-incubated

with

sCD

4–

complem

entmediated

virolysisofM

Nand

IIIBin

thepresence

ofsCD

4[S

pearetal.(1993)]

•50-69:

Epitope

describedas

ClusterI,601-604,conform

ational–does

notneutralizeIIIB

orsynergizeneutralization

byanti-V

3M

Ab

447-52Dor

byC

D4

BS

MA

bs[Laaletal.(1994)]

•50-69:

One

ofseveral

anti-gp41M

Abs

thatbind

toa

gp41-maltose

bindingfusion

proteindesigned

tostudy

theleucine

zipperdom

ainofgp41,show

ingthatthe

constructhasretained

aspectsofnorm

algp41conform

ation[C

henetal.(1995)]

•50-69:

Preferentially

bindsoligom

er–

bindingincreased

afterpretreatm

entof

infectedcells

with

sCD

4–

bindingdom

ainoverlaps

sitethatis

criticalforgp120-gp41

association,avE

ry[S

attentauetal.(1995)]

•50-69:

Virions

complexed

togp41

Ab

facilitatepresentation

ofp66R

Tepitopes

toT

hcells

[Manca

etal.(1995)]•

50-69:D

oesnotneutralize

HIV

-1LA

I[McD

ougaletal.(1996)]•

50-69:P

rebindingofanti-V

3,and

CD

4iMA

bs48d

and17b,

butnotanti-V2

neutralizingM

Abs,

exposethe

50-69epitope

[Poignard

etal.(1996a)]•

50-69:B

indsto

alinear

epitopelocated

inthe

Cluster

Iregion–

bindingof50-69

and240-D

inhibitedby

Fabs

A1,

A4,M

8B,M

26B,M

12Band

T2

[Binley

etal.(1996)]•

50-69:U

sedto

testexposureofgp41

uponsC

D4

binding[K

lasse&

Sattentau(1996)]

•50-69:

Binding

ofanti-gp120M

Abs

IgG1b12

or654-30Ddoes

notmediate

significantexposureofthe

gp41epitopes

forM

Abs

2F5

and50-69

[Stam

atatosetal.(1997)]

Page 14: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-219

DE

C98

677cont.

•50-69:

Abs

thatrecognize

discontinuousepitopes

canidentify

mim

otopesfrom

aphage

peptidedisplay

library–

50-69m

apsto

anim

munodom

inantdom

ainin

gp41–

threegroups

ofpeptides

were

selected,one

which

seems

most

closelyrelated

togp41

sequencepeptide

consensusis

WG

Cxx(R

K)(x

n )LxC–

theanalogous

gp41sequence

WG

CS

GK

LICis

presentinm

ostMgroup

clades,exceptDw

itha

comm

onL

toH

substitution[B

ootsetal.(1997)]

•50-69:

Mutations

inB

H10

gp160,W

596Yand

T605A

,as

well

asdeletions

of605-609

(TTAV

P)

and597-609

(GC

SG

KLIC

TTAV

P),

abrogatebinding

ofenhancing

MA

bs86,

240D,

50-69,and

246-D–

5/6enhancing

MA

bsidentified

todate

bindto

theim

munodom

inantregion579-613

–identifies

non-contiguousW

596-G597-C

598...C604-

T605

asm

inimalepitope

[Mitchelletal.(1998)]

•50-69:

NIH

AID

SR

esearchand

Reference

ReagentP

rogram:

531

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

678F

abA

1gp41(584-609

LAI)

gp41(69-98)R

ILAVE

RY

LKD

QQ

LLGI-

WG

CS

GK

LICT

TAVN

HIV

-1infection

human(IgG1

κ )

Donor:

Susan

Zolla-P

azner,NY

U,N

YR

eferences:[Binley

etal.(1996)]N

OT

ES

:•

Fab

A1:

Binds

toC

lusterI

region–

competes

with

MA

bs240-D

and50-69

–conform

ationsensitive

–variable

regionssequenced

[Binley

etal.(1996)]

679F

abA

4gp41(584-609

LAI)

gp41(69-98)R

ILAVE

RY

LKD

QQ

LLGI-

WG

CS

GK

LICT

TAVN

HIV

-1infection

human(IgG1

κ )

Donor:

Susan

Zolla-P

azner,NY

U,N

YR

eferences:[Binley

etal.(1996)]N

OT

ES

:•

Fab

A4:

Binds

toC

lusterI

region–

competes

with

MA

bs240-D

and50-69

–conform

ationsensitive

–variable

regionssequenced

[Binley

etal.(1996)]

680F

abM

8Bgp41(584-609

LAI)

gp41(69-98)R

ILAVE

RY

LKD

QQ

LLGI-

WG

CS

GK

LICT

TAVN

HIV

-1infection

human(IgG1

κ )

Donor:

Susan

Zolla-P

azner,NY

U,N

YR

eferences:[Binley

etal.(1996)]N

OT

ES

:•

Fab

M8B

:B

indsto

Cluster

Iregion

–com

petesw

ithM

Abs

240-Dand

50-69–

conformation

sensitive–

variableregions

sequenced[B

inleyetal.(1996)]

Page 15: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-220

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

681F

abM

26Bgp41(584-609

LAI)

gp41(69-98)R

ILAVE

RY

LKD

QQ

LLGI-

WG

CS

GK

LICT

TAVN

HIV

-1infection

human(IgG1

κ )

Donor:

Susan

Zolla-P

azner,NY

U,N

YR

eferences:[Binley

etal.(1996)]N

OT

ES

:•

Fab

M26B

:B

indsto

Cluster

Iregion

–com

petesw

ithM

Abs

240-Dand

50-69–

conformation

sensitive–

variableregions

sequenced[B

inleyetal.(1996)]

682F

abT

2gp41(584-609

LAI)

gp41(69-98)R

ILAVE

RY

LKD

QQ

LLGI-

WG

CS

GK

LICT

TAVN

HIV

-1infection

human(IgG1

κ )

Donor:

Susan

Zolla-P

azner,NY

U,N

YR

eferences:[Binley

etal.(1996)]N

OT

ES

:•

Fab

T2:

Binds

toC

lusterI

region–

competes

with

MA

bs240-D

and50-69

–conform

ationsensitive

–variable

regionssequenced

[Binley

etal.(1996)]

683F

abM

12Bgp41(584-609

LAI)

gp41(69-98)R

ILAVE

RY

LKD

QQ

LLGI-

WG

CS

GK

LICT

TAVN

HIV

-1infection

human(IgG1

κ )

Donor:

Susan

Zolla-P

azner,NY

U,N

YR

eferences:[Binley

etal.(1996)]N

OT

ES

:•

Fab

M12B

:B

indsto

Cluster

Iregion

–com

petesw

ithM

Abs

240-Dand

50-69–

conformation

sensitive–

variableregions

sequenced[B

inleyetal.(1996)]

68441.4

gp41(584-609)gp41(69-98)

RILAV

ER

YLK

DQ

QLLG

I-W

GC

SG

KLIC

TTAV

Donor:

JanM

cClure,B

ristol-Myers

Squibb

Pharm

aceuticalRes

Inst,Seattle,W

AR

eferences:[Pincus

&M

cClure(1993)]

NO

TE

S:

•41.4:

Binds

topeptide

weakly,butto

gp160w

ithhigher

affinitythan

41.1,andcross-com

petesw

ith41.1

–probably

conformational–

MA

bw

ascoupled

toricin

Achain

(RA

C)

–sC

D4

enhancesthe

efficacyofim

munotoxins

invitro

30-fold[P

incus&

McC

lure(1993)]

Page 16: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-221

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

68541-1

gp41(584-609)gp41(69-98)

RILAV

ER

YLK

DQ

QLLG

I-W

GC

SG

KLIC

TTAV

gp160m

urine(IgG1κ )

Donor:

JanM

cClure,B

ristol-Myers

Squibb

Pharm

aceuticalRes

Inst,Seattle,W

AR

eferences:[Gosting

etal.(1987),Dalgleish

etal.(1988),Pincus

etal.(1991),Pincus

&M

cClure(1993),M

anietal.(1994),P

incusetal.(1996),P

incusetal.(1998)]

NO

TE

S:

•41-1:

This

antibodygp41(584-609)

[Manietal.(1994)]seem

sto

havebeen

named

thesam

eas

adifferentM

Ab

togp41(735-752

IIIB)

[Dalgleish

etal.(1988)]•

41-1:A

lsocalled

41.1,although

possiblynot,

theliterature

isconfusing

becausetw

ogp41

MA

bsthat

bindto

thisregion

with

similar

names

(dashversus

period)are

listedas

murine

andhum

an•

41-1:B

roadlyreactive

[Gosting

etal.(1987)]•

41-1:T

hisantibody

seems

tohave

beennam

edthe

same

asa

differentMA

bto

gp41(735-752)[Dalgleish

etal.(1988)]•

41-1:E

fficaciousas

anim

munotoxin

when

coupledto

RA

C–

gavelinear

epitopeas

gp160579-603

[Pincus

etal.(1991)]•

41-1:C

alled41.1,

anddescribed

asa

human

MA

b–

cross-competes

with

41.4–

sCD

4enhances

theefficacy

ofim

munotoxins

invitro

30-fold–

MA

bw

ascoupled

toricin

Achain

(RA

C)

–[P

incus&

McC

lure(1993)]•

41-1:D

idnot

requirethe

C-C

disulfidebridge

andloop

formation,

canbind

simultaneously

with

9-11[M

anietal.(1994)]

•41-1:

Called

41.1,and

describedas

ahum

anM

Ab,

binding579-60

4–

apanel

ofim

munotoxins

was

generatedby

linkingE

nvM

Abs

toricin

A–

imm

unotoxinsm

ediatedcellkilling,

butkilling

was

notdirectly

proportionaltobinding

[Pincus

etal.(1996)]

6869-11

gp41(584-609)gp41(69-94)

RILAV

ER

YLK

DQ

QLLG

I-W

GC

SG

KLIC

gp160m

urine(IgG1 )

Donor:

JanM

cClure,B

ristol-Myers

Squibb

Pharm

aceuticalRes

Inst,Seattle,W

AR

eferences:[Manietal.(1994)]

NO

TE

S:

•9-11:

requiredthe

C-C

disulfidebridge

andloop

formation,can

bindsim

ultaneouslyw

ith41-1

[Manietal.(1994)]

687polyclonal

gp41(589-596)gp41

(72-79)AV

ER

YLK

DH

IV-1

infectionhum

ansera

Donor:

JanM

cClure,B

ristol-Myers

Squibb

Pharm

aceuticalRes

Inst,Seattle,W

AR

eferences:[Klasse

etal.(1991)]N

OT

ES

:•

Substitutions

anddeletions

inpeptide

583-599w

eresystem

aticallystudied

–alterations

inAV

ER

YLK

Dabrogated

theantigenicity

ofpeptidesw

ithm

ostof14hum

ansera

[Klasse

etal.(1991)]

Page 17: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-222

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

688polyclonal

gp41(583-599)gp41

(66-82)LQ

AR

ILAVE

RY

LKD

QQ

LH

IV-1

infectionhum

ansera

Donor:

JanM

cClure,B

ristol-Myers

Squibb

Pharm

aceuticalRes

Inst,Seattle,W

AR

eferences:[Klasse

etal.(1993b)]N

OT

ES

:•

42H

IV-1

positivehum

ansera

were

testedagainstW

Tpeptide,and

peptidew

ithsubstitution

589A

toT

:11/42reacted

stronglyw

ithW

T,weakly

with

A589T

–31

reactedw

eaklyw

ithparental,even

more

weakly

with

substituted[K

lasseetal.(1993b)]

6899G

5Agp41(596-599

IIIB)

gp41(81-84)

QLLG

Anti-idiotype

againstM

38m

urine(IgM)

Donor:

JanM

cClure,B

ristol-Myers

Squibb

Pharm

aceuticalRes

Inst,Seattle,W

AR

eferences:[Lopalcoetal.(1993),B

eretta&

Dalgleish(1994)]

NO

TE

S:

•9G

5A:A

nti-idiotypeto

gp120C

terminus

(C5

region)M

Ab

M38

[Lopalcoetal.(1993)]

6903D

6gp41(604-617

BH

10)gp41(89-103)

SG

KLIC

TTAV

PW

NA

SH

IV-1

infectionhum

an(IgG1κ )

Donor:

H.K

atinger,Inst.A

ppl.M

icrobiol.,Vienna,A

ustriaand

ViralTesting

System

s,Houston,T

XR

eferences:[Felgenhaueretal.(1990),H

eetal.(1992),C

henetal.(1994b),S

attentauetal.(1995),W

isnewskietal.(1996)]

NO

TE

S:

•3D

6:S

equenceofcD

NA

encodingV

-regions

[Felgenhauer

etal.(1990)]•

3D6:

Fab

fragmentcrystalstructure

[He

etal.(1992)]•

3D6:

This

MA

bbinds

toH

IVgp41,and

toa

43kd

proteinfound

inhum

anT,B

andm

onocytecelllines,proposed

molecular

mim

icry[C

henetal.(1994b)]

•3D

6:C

alledIA

M41-3D

6:binding

increasedafter

pretreatment

ofinfected

cellsw

ithsC

D4

–binding

domain

overlapssite

thatiscriticalfor

gp120-gp41association,ctta

V[S

attentauetal.(1995)]

•3D

6:3D

6is

VH

3–

V-region

heavychain

usagew

asexam

inedand

abias

ofenhancedV

H1

andVH

4,andreduced

VH

3,was

notedam

ongH

IVinfected

individuals[W

isnewskietal.(1996)]

Page 18: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-223

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

691120-16

gp41(644-663H

XB

2)gp41(134-153)

SLIE

ES

QN

QQ

EK

NE

QE

L-LE

LN

HIV

-1infection

human(IgG2

κ )

Donor:

H.K

atinger,Inst.A

ppl.M

icrobiol.,Vienna,A

ustriaand

ViralTesting

System

s,Houston,T

XR

eferences:[Andris

etal.(1992),Robinson

Jr.etal.(1990a),Tyleretal.(1990),X

uetal.(1991),R

obinsonJr.

etal.(1991),E

ddlestonetal.(1993),F

orthaletal.(1995),Wisnew

skietal.(1996)]N

OT

ES

:•

120-16:A

lsocalled

SZ

-120.16•

120-16:A

ntibodydependentenhancem

ent(AD

E)ofH

IV-1

IIIBinfectivity,synergistically

enhancedby

MA

bV

10-9[R

obinsonJr.

etal.(1990a)]•

120-16:P

otentAD

CC

(incontrastto

MA

b98-43,gp41(579-604))

[Tyleretal.(1990)]

•120-16:

Lessreactive

regionthan

AVE

RY

region–

mostA

bsinvolving

thisregion

boundconform

ationalepitopes,this

was

theonly

linearone

[Xu

etal.(1991)]•

120-16:S

ynergizesw

ithhuM

Ab

50-69in

vitroto

enhanceH

IV-1

infection[R

obinsonJr.

etal.(1991)]•

120-16:C

alledS

Z-120.16

[Eddleston

etal.(1993)]•

120-16:N

oneutralizing

activity,bothA

DC

Cand

viralenhancingactivity

[Forthaletal.(1995)]

•120-16:

120-16is

VH4

–V

-regionheavy

chainusage

was

examined

anda

biasof

enhancedV

H1

andVH

4,and

reducedVH

3,was

notedam

ongH

IVinfected

individuals[W

isnewskietal.(1996)]

692D

50gp41(642-665)

gp41(132-155)D

ISC

ON

TIN

UO

US

dimeric

Env

murine

Donor:

H.K

atinger,Inst.A

ppl.M

icrobiol.,Vienna,A

ustriaand

ViralTesting

System

s,Houston,T

XR

eferences:[Earletal.(1994),B

inleyetal.(1996),R

ichardsonJr

etal.(1996),Earletal.(1997)]

NO

TE

S:

•D

50:T

houghtto

bea

discontinuousepitope

recognizingresidues

between

649-668–

designatedcluster

II–

Fabs

D5,D

11,G1,T

3,M12,M

15,S6,S

8,S9,S

10block

binding[B

inleyetal.(1996)]

•D

50:R

ichardsonsuggests

thisis

alinear

gp41epitope

[Richardson

Jretal.(1996)]

•D

50:F

oundto

bindto

alinear

peptide,betw

eenenv

amino

acids642-655

–can

beblocked

bythe

conformation

dependentMA

bsD

16,D17,D

31,D36,D

37,D40,D

44,D55,D

59,T37,and

T45

–the

regionis

inthe

imm

unogeniccluster

two

region–

reactivew

ith9/10

HIV

-1strains

tested,allexceptHIV

-1A

DA

,inw

hichthe

changeE

659Dand

E662A

may

resultinthe

lossofbinding

(ELLE

toD

LLA)

[Earletal.(1997)]

Page 19: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-224

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

69398-6

gp41(644-663H

XB

2)gp41(134-153)

SLIE

ES

QN

QQ

EK

NE

QE

L-LE

LN

HIV

-1infection

human(IgG2

κ )

Donor:

H.K

atinger,Inst.A

ppl.M

icrobiol.,Vienna,A

ustriaand

ViralTesting

System

s,Houston,T

XR

eferences:[Pinter

etal.(1989),

Gorny

etal.(1989),

Till

etal.(1989),

Robinson

Jr.et

al.(1990a),Tyler

etal.(1990),

Andris

etal.(1992),Sattentau

&M

oore(1991),Robinson

Jr.etal.(1991),X

uetal.(1991),E

ddlestonetal.(1993),S

pearet

al.(1993),Taniet

al.(1994),Laalet

al.(1994),C

henet

al.(1995),F

orthaletal.(1995),

Manca

etal.(1995),

Sattentau

etal.(1995),Wisnew

skietal.(1996)]N

OT

ES

:•

98-6:R

eactspreferentially

with

gp160oligom

er,compared

togp41

monom

er[P

interetal.(1989)]

•98-6:

Kills

HIV

-infectedcells

when

coupledto

deglycosylatedricin

Achain

[Gorny

etal.(1989)]•

98-6:Toxic

toH

IV-infected

Tcells

(H9)

andm

onocytes(U

937)w

hencoupled

todeglycosylated

Achain

ofricin

[Tilletal.(1989)]

•98-6:

No

neutralizingor

enhancingactivity

forH

IV-1

IIIB[R

obinsonJr.

etal.(1990a)]•

98-6:S

ervesas

targetforantibody-dependentcellular

cytotoxicity,AD

CC

[Tyleretal.(1990)]

•98-6:

Two

foldincrease

inbinding

togp120

inthe

presenceofbound

sCD

4[S

attentau&

Moore(1991)]

•98-6:

No

neutralizingor

enhancingactivity

[Robinson

Jr.etal.(1991)]

•98-6:

Appeared

tobe

specificfor

aconform

ationalordiscontinuous

epitope[X

uetal.(1991)]

•98-6:

Called

SZ

-98.6–

bindsto

aconform

ationaldomain

within

aa644-663

ofgp41,andreacts

with

astrocytes,asdo

167-7and

ND

-15G1

[Eddleston

etal.(1993)]•

98-6:D

idnotm

ediatedeposition

ofcomplem

entcomponentC

3on

HIV

infectedcells,binding

enhancedby

sCD

4[S

pearetal.(1993)]

•98-6:

This

MA

bw

asexpressed

asa

surfaceanti-gp41

monoclonalantibody

receptorfor

gp41on

aC

D4-negative

B-cellline.

Transfected

cellscould

bindH

IVenvelope,

butcould

notbe

infectedby

HIV

-1.W

henC

D4

deliveredby

retroviralconstructs

was

expressedon

thesecells,

theyacquired

theability

toreplicate

HIV

-1,and

sIg/gp41specifically

enhancedviralreplication

[Tanietal.(1994)]•

98-6:E

pitopedescribed

asC

lusterII,644-663,conformational–

doesnotneutralize

IIIBorsynergize

neutralizationby

anti-V3

MA

b447-52D

orby

CD

4B

SM

Abs

[Laaletal.(1994)]•

98-6:O

neof

severalanti-gp41

MA

bsthat

bindto

agp41-m

altosebinding

fusionprotein

designedto

studythe

leucinezipper

domain

ofgp41,showing

thattheconstructhas

retainedaspects

ofnormalgp41

conformation

[Chen

etal.(1995)]•

98-6:N

oneutralizing

activity,positiveA

DC

Cactivity,and

noviralenhancing

activity[F

orthaletal.(1995)]•

98-6:V

irionscom

plexedto

gp41A

bfacilitate

presentationofp66

RT

epitopesto

Th

cells[M

ancaetal.(1995)]

•98-6:

Preferentially

recognizesoligom

ericform

ofgp41

–enhanced

bindingto

HIV

-1infected

cellsat

37degrees

relativeto

4degrees

–addition

ofsCD

4enhances

binding[S

attentauetal.(1995)]

•98-6:

98-6is

VH4

–V

-regionheavy

chainusage

was

examined

anda

biasofenhanced

VH

1and

VH

4,andreduced

VH

3,was

notedam

ongH

IVinfected

individuals[W

isnewskietal.(1996)]

•98-6:

NIH

AID

SR

esearchand

Reference

ReagentP

rogram:

1240

Page 20: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-225

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

694167-7

gp41(644-663)gp41(134-153)

SLIE

ES

QN

QQ

EK

NE

QE

L-LE

LH

IV-1

infectionhum

an(IgG2λ )

Donor:

H.K

atinger,Inst.A

ppl.M

icrobiol.,Vienna,A

ustriaand

ViralTesting

System

s,Houston,T

XR

eferences:[Xu

etal.(1991),Eddleston

etal.(1993)]N

OT

ES

:•

167-7:S

pecificfor

aconform

ationalepitope[X

uetal.(1991)]

•167-7:

Called

SZ

-167.7–

bindsto

aconform

ationaldomain

within

aa644-663

ofgp41,andreacts

with

astrocytes,as

do98-6

andN

D-15G

1[E

ddlestonetal.(1993)]

695N

D-15G

1gp41(644-663

HX

B2)

gp41(134-153)S

LIEE

SQ

NQ

QE

KN

EQ

EL-

LEL

HIV

-1infection

human(IgG1

κ )

Donor:

?R

eferences:[Eddleston

etal.(1993)]N

OT

ES

:•

ND

-15G1:

Mapped

tothe

conformational

epitopew

ithinaa

644-663,and

reactsw

ithastrocytes,

asdo

98-6and

167-7[E

ddlestonetal.(1993)]

696167-D

gp41(644-663H

XB

2)gp41(134-153)

SLIE

ES

QN

QQ

EK

NE

QE

L-LE

LN

HIV

-1infection

human(IgG1

λ )

Donor:

?R

eferences:[Spear

etal.(1993),Forthaletal.(1995),M

ancaetal.(1995)]

NO

TE

S:

•167-D

:D

idnot

mediate

depositionof

complem

entcom

ponentC

3on

HIV

infectedcells

–com

plement

mediated

virolysisofM

Nand

IIIBin

thepresence

ofsCD

4[S

pearetal.(1993)]

•167-D

:No

neutralizingactivity,no

AD

CC

activity,andno

viralenhancingactivity

[Forthaletal.(1995)]

•167-D

:Virions

complexed

togp41

Ab

facilitatepresentation

ofp66R

Tepitopes

toT

hcells

[Manca

etal.(1995)]

Page 21: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-226

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

6972F

5gp41(662-667

BH

10)gp41(152-157)

ELD

KW

AL

PH

IV-1

infectionhum

an(IgG3κ )

Donor:

Herm

annK

atinger,U

.of

Bodenkultur,

orP

olymun

Scientific

Inc.,V

ienna,A

ustria;V

iralTesting

System

s,H

ouston,TX

,US

AR

eferences:[Buchacheretal.(1992),M

usteretal.(1993),Allaw

ayetal.(1993),K

lasseetal.(1993a),P

urtscheretal.(1994),Laaletal.(1994),B

uchacheretal.(1994),D’S

ouzaetal.(1994),C

onleyetal.(1994b),T

halietal.(1994),Chen

etal.(1994b),M

usteret

al.(1994),B

eretta&

Dalgleish(1994),

D’S

ouzaet

al.(1995),T

rkolaet

al.(1995),S

attentauet

al.(1995),M

oore&

Ho(1995),

Neurath

etal.(1995),

Kessler

2ndet

al.(1995),C

alarotaet

al.(1996),M

cKeating(1996),

Poignard

etal.(1996b),

Sattentau(1996),

Conley

etal.(1996),

Pincus

etal.(1996),

McK

eatinget

al.(1996),S

toiberet

al.(1996),P

urtscheretal.(1996),Schutten

etal.(1997),D’S

ouzaetal.(1997),M

oetal.(1997),Lietal.(1997),K

esslerIIetal.(1997),M

oore&

Trkola(1997),M

ascolaetal.(1997),S

tamatatos

etal.(1997),Turbica

etal.(1997),Ugolinietal.(1997),B

urton&

Montefiori(1997),E

arletal.(1997),Andrus

etal.(1998),Mondor

etal.(1998),Connor

etal.(1998),Yang

etal.(1998),T

rkolaetal.(1998),F

outsetal.(1998),E

rnstetal.(1998),Takefman

etal.(1998),Lietal.(1998)]N

OT

ES

:•

2F5:

Also

calledIA

M2F

5,IAM

-41-2F5,IA

M2F

5•

2F5:

DK

WA

definedas

thecore

sequence–

highlyconserved

epitopeneutralizing

MA

b[B

uchacheret

al.(1992),M

usteretal.(1993)]

•2F

5:S

ynergyw

ithcom

binationsofC

D4-based

molecules

ininhibition

ofHIV

-1E

nvm

ediatedcellfusion

[Allaw

ayetal.(1993)]

•2F

5:C

alledIA

M-41-2F

5–

reportsM

Ab

tobe

IgG1 –the

gp41m

utation582(A

lato

Thr)

resultsin

conformational

changesin

gp120thatconfer

neutralizationresistance

toconform

ationallysensitive

neutralizingM

Abs

–neutraliza-

tionefficiency

of2F5

isnotaffected

[Klasse

etal.(1993a)]•

2F5:

Broadly

reactiveneutralizing

activity,E

LDK

WA

isrelatively

conserved–

neutralized2

primary

isolates[P

urtscheretal.(1994)]

•2F

5:F

ailedto

showsynergy

with

anti-CD

4binding

siteIIIB

neutralizingantibodies

[Laaletal.(1994)]•

2F5:

MA

bgenerated

byelectrofusion

ofP

BL

fromH

IV-1

positivevolunteers

with

CB

-F7

cells[B

uchacheretal.(1994)]

•2F

5:Included

ina

multi-lab

studyfor

antibodycharacterization

bindingand

neutralizationassay

comparison

[D’S

ouzaetal.(1994)]

•2F

5:C

alledIA

M-41-2F

5–

neutralizedlab

andprim

aryisolates

–t

1/2

dissociation122

min

forthe

peptide,and156

min

forgp41

–core

D(K

/R)W

–A

bresistantisolate

hadthe

sequenceK

LDN

WA

[Conley

etal.(1994b)]•

2F5:

gp41m

utation(582

A/T

)thatreducesneutralization

ofanti-CD

4binding

siteM

Abs

doesnotalter2F

5’sability

toneutralize

[Thalietal.(1994)]

•2F

5:2F

5epitope

ELD

KW

Ainserted

intoan

imm

unogenicloop

ininfluenza

virushem

agglutinincan

elicitIIIB,M

Nand

RF

neutralizingsera

inim

munized

mice

[Muster

etal.(1994)]•

2F5:

Found

toneutralize

MN

,JRC

SF,and

two

Bsubtype

primary

isolates,butnota

Dsubtype

primary

isolate,bym

ostlabsin

am

ulti-laboratorystudy

involving11

labs[D

’Souza

etal.(1995)]•

2F5:

Cross-clade

primary

virusneutralizing

activity–

LDK

Wdefined

asthe

coreepitope

[Trkola

etal.(1995)]

Page 22: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-227

DE

C98

697cont.

•2F

5:C

alledIA

M41-2F

5–

exposedin

thepresence

ofgp120

onthe

cellsurface,w

hilem

ostof

gp41is

masked

–binds

proximalto

transmem

braneregion

[Sattentau

etal.(1995)]•

2F5:

Review

:binds

tothe

onlygenerally

acceptedstrong

neutralizingepitope

outsideofgp120,one

ofonly3

MA

bsw

ithstrong

broadactivity

againstprim

aryviruses,

theothers

are2G

12and

IgG1b12

–unique

mem

berof

epitopecluster

[Moore

&H

o(1995)]andJohn

Moore,per

comm

1996•

2F5:

MA

bbinding

decreasesthe

accessibilityor

altersthe

conformation

ofthe

gp41fusion

domain

andof

gp120dom

ains,includingthe

bindingsite

forthe

CD

4cellreceptor

[Neurath

etal.(1995)]•

2F5:

Broad

cross-cladeneutralization

ofprimary

isolates–

additiveneutralization

incom

binationw

ithanti-C

D4B

SM

Ab

IgG1b12

(Called

BM

12)[K

essler2nd

etal.(1995)]•

2F5:

Only

4/20A

rgentinianand

3/43S

wedish

HIV

+sera

reactedw

ithLLE

LDK

WA

SL

–sera

reactingw

ithpeptides

thatcontainedE

LDK

WA

tendedto

havehigh

neutralizationtiters

–the

regioncarboxylterm

inaltoE

DLK

WA

was

foundto

bem

oreim

portantfor

polyclonalseraA

Bbinding,

670-675W

NW

FD

I–

2F5

boundm

oststrongly

tothe

peptideQ

ELLE

LDK

WA

[Calarota

etal.(1996)]•

2F5:

ELD

KW

AS

isin

agp41

bindingregion

forthe

negativeregulator

ofcom

plement

factorH

(CF

H)

–A

bsto

HIV

generallydo

notcauseefficientcom

plement-m

ediatedlysis,butbinding

of2F5

caninterfere

with

CH

Fbinding,

facilitatingH

IVdestruction

bycom

plement[S

toiberetal.(1996)]

•2F

5:P

rimary

isolatesfrom

cladeA

,B

,and

Eare

neutralizedby

2F5

–neutralization

requiresthe

LDK

Wm

otif–

neutralizationresistantisolates

or2F

5selected

variantsallhad

substitutionsin

theD

orK

[Purtscher

etal.(1996)]•

2F5:

Neutralizes

HX

B2,

primary

isolates,and

chimeric

virusw

ithgp120

fromprim

aryisolates

inan

HX

B2

back-ground

[McK

eatingetal.(1996)]

•2F

5:R

eview:

oneofthree

MA

bs(IgG

1b12,2G12,and

2F5)generally

acceptedas

havingsignificantpotency

againstprim

aryisolates

[Poignard

etal.(1996b)]•

2F5:

Review

:only

fourepitopes

havebeen

describedw

hichcan

stimulate

auseful

neutralizingresponse

toa

broadspectrum

ofprimary

isolates,represented

bythe

bindingsites

ofMA

bs:447-52-D

,2G12,

Fab

b12,and

2F5

[Sattentau(1996)]

•2F

5:2F

5w

asinfused

intotw

ochim

panzeesw

hichw

erethen

givenan

intravenouschallenge

with

aprim

aryH

IV-1

isolate–

bothbecam

einfected,butw

ithdelayed

detectionand

prolongeddecrease

inviralload

relativeto

controls,indicating

thatpreexisting,

neutralizingantibodies

(passivelyadm

inisteredor

activelyelicited)

affectthe

courseof

acute-phasevirus

replicationand

canbe

influentialaftertheA

bcan

nolongerbe

detectedin

theperipheralcirculation

[Conley

etal.(1996)]•

2F5:

Apanelofim

munotoxins

were

generatedby

linkingE

nvM

Abs

torici

nA

–im

munotoxins

mediated

cellkilling,butkilling

was

notdirectlyproportionalto

binding[P

incusetal.(1996)]

•2F

5:C

alledIA

M2F

5–

antibodym

ediatedenhancem

entor

inhibitionseem

edto

bedeterm

inedby

isolaterather

thanantibody

specificity–

inthis

study,only

2F5

inhibitedthe

entryofallthe

virusesstudied,

irrespectiveoftheir

phenotype,anddirectly

proportionaltoits

affinityto

monom

ericH

IV-1

gp160[S

chuttenetal.(1997)]

•2F

5:O

fthreeneutralizing

MA

bs(257-D

,IgG1b12,and

2F5),2F

5w

asthe

onlyone

toinhibitthe

entryofallviruses

studied,bothS

IandN

SI,w

itha

potencyproportionalto

itsaffinity

form

onomeric

gp126[S

chuttenetal.(1997)]

Page 23: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-228

DE

C98

697cont.

•2F

5:In

am

ultilabevaluation

ofmonoclonalantibodies,only

IgG1b12,2G

12,and2F

5could

neutralizeatleasthalf

ofthe9

primary

testisolatesata

concentrationof

<25µ

gper

mlfor

90%viralinhibition

–the

isolatesw

ithno

2F5

neutralizingsusceptibility

hadthe

sequencesA

LGQ

WA

orE

LDT

WA

insteadof

ED

LKW

A–

7/9prim

aryisolates

were

neutralized,andA

LDK

WQ

andA

LDK

WA

were

susceptibleto

neutralization[D

’Souza

etal.(1997)]•

2F5:

AJR

CS

Fvariant

thatw

asselected

forIgG

1b12resistance

remained

sensitiveto

MA

bs2G

12and

2F5,

forcom

binationtherapy

[Mo

etal.(1997)]•

2F5:

One

of14

human

MA

bstested

forability

toneutralize

achim

ericS

HIV

-vpu+,

which

expressedH

IV-1

IIIBenv

–strong

neutralizerof

SH

IV-vpu+

–all

Ab

combinations

testedshow

edsynergistic

neutralization–

2F5

hassynergistic

responsew

ithM

Abs

694/98-D(anti-V

3),2G12,b12,and

F105

[Lietal.(1997)]•

2F5:

IgG1b12

was

more

potentw

ithgreater

breadththan

MA

b2F

5in

aninfection

reductionassay

including35

primary

isolates[K

esslerIIetal.(1997)]

•2F

5:R

eview:

MA

Bs

2F5,

2G12

andIgG

1b12have

potentialfor

usein

combination

with

CD

4-IgG2

asan

im-

munotherapeutic

orim

munoprophylactic

–hom

ologousM

Abs

tothese

arerare

inhum

ansand

vaccinestrategies

shouldconsider

includingconstructs

thatmay

enhanceexposure

oftheseM

Abs’epitopes

[Moore

&T

rkola(1997)]•

2F5:

Binding

ofanti-gp120M

Abs

IgG1b12

or654-30D

doesnotm

ediatesignificantexposure

ofthegp41

epitopesfor

MA

bs2F

5and

50-69[S

tamatatos

etal.(1997)]•

2F5:

Using

concentrationsofA

bsachievable

invivo,the

triplecom

binationof2F

5,2G12

andH

IVIG

was

foundto

besynergistic

tohave

thegreatestbreadth

andm

agnitudeofresponse

against15clade

Bprim

aryisolates

[Mascola

etal.(1997)]•

2F5:

Used

tostandardize

polyclonalresponseto

CD

4B

S[T

urbicaetal.(1997)]

•2F

5:T

heonly

MA

boutofa

largepanelto

showno

correlationbetw

eenV

iralbindinginhibition

andneutralization

[Ugolinietal.(1997)]

•2F

5:T

hisreview

summ

arizesresults

about2F

5:it

bindsextracellularly,

nearthe

transmem

branedom

ain,it

isthe

onlygp41

MA

bthatis

neutralizing,itreacts

with

many

non-Bclade

virusesand

hasa

paradoxicallyw

eakbinding

tovirus,given

theneutralizing

titres[B

urton&

Montefiori(1997)]

•2F

5:P

ost-exposureprophylaxis

was

effectivew

henM

Ab

694/98-Dw

asdelivered

15m

inpost-exposure

toH

IV-1

LAI

inhu-P

BL-S

CID

mice,

butdeclined

to50%

ifdelivered

60m

inpost-exposure,

andsim

ilartim

econstraints

havebeen

observedfor

HIV

IG,2F

5and

2G12,in

contrasttoM

Ab

BAT

123thatcould

protectdelivered4

hourspost

infection[A

ndrusetal.(1998)]

•2F

5:T

hisM

Ab

andthe

resultsof

[Ugoliniet

al.(1997)]are

discussed–

theauthors

proposethat

anA

bbound

togp41

would

typicallyprojectless

fromthe

surfaceofthe

virionand

sobe

unableto

interferew

ithattachm

ent[Parren

etal.(1998)]•

2F5:

Ab

fromgp120

vaccinatedindividuals

priorto

infection,w

hosubsequently

became

HIV

infected,could

notachieve

90%neutralization

ofthe

primary

virusby

which

theindividuals

were

ultimately

infected–

theseviruses

were

notparticularly

refractiveto

neutralization,as

determined

bytheir

susceptibilityto

neutralizationby

MA

bs2G

12,IgG1b12,2F

5and

447-52D[C

onnoretal.(1998)]

Page 24: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-229

DE

C98

697cont.

•2F

5:A

neutralizationassay

was

developedbased

onhem

inestedP

CR

amplification

ofthe

LTR

(HN

PC

R)

–LT

R-

HN

PC

Rconsistently

revealedH

IVD

NA

andw

asshow

nto

bea

rapid,specificand

reliableneutralization

assaybased

ontests

with

6M

Abs

and5

isolates[Y

angetal.(1998)]

•2F

5:A

wide

rangeofneutralizing

titersw

asobserved

thatwas

independentofco-receptorusage–

2F5

was

them

ostpotentofthe

MA

bstested

[Trkola

etal.(1998)]•

2F5:

Points

outthat

2G12

and2F

5,potent

neutralizingantibodies,

were

identifiedby

screeningfor

cellsurface

(oligomeric

envelope)reactivity

[Fouts

etal.(1998)]•

2F5:

The

ELD

KW

Aepitope

was

insertedinto

theantigenic

siteB

ofinfluenza

hemagglutinin

andexpressed

onbaculovirus

infectedinsect

cells,flanked

by3

additionalrandomam

inoacids,

xELD

KW

Axx

–FA

CS

was

usedto

isolatethe

clonethat

displayedthe

epitopew

iththe

most

markedly

increasedbinding

capacityfor

2F5,

toidentify

particularlyspecific

imm

unogenicconstructs

–P

ELD

KW

AP

Pw

asa

highaffinity

formselected

byFA

CS

[Ernst

etal.(1998)]•

2F5:

Inducescom

plement-m

ediatedlysis

inM

Nbut

notprim

aryisolates

–prim

aryisolates

arerefractive

toC

ML

[Takefman

etal.(1998)]•

2F5:

Neutralization

synergyw

asobserved

when

theM

Abs

694/98-D(V

3),2F5

(gp41),and2G

12(gp120

discontin-uous)

were

usedin

combination,and

evengreater

neutralizingpotentialw

asseen

with

theaddition

ofafourth

MA

b,F

105(C

D4

BS

)[Lietal.(1998)]

•2F

5:U

KM

edicalResearch

CouncilA

IDS

reagent:A

RP

3063•

2F5:

NIH

AID

SR

esearchand

Reference

ReagentP

rogram:

1475

Page 25: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-230

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

698polyclonal

gp41(662-667B

H10)

gp41(152-157)E

LDK

WA

Lchim

ericinfluenza

virus/ELD

KW

Am

urine(IgG,IgA

)

Donor:

Herm

annK

atinger,U

.of

Bodenkultur,

orP

olymun

Scientific

Inc.,V

ienna,A

ustria;V

iralTesting

System

s,H

ouston,TX

,US

AR

eferences:[Muster

etal.(1994),Muster

etal.(1995)]N

OT

ES

:•

Sustained

ELD

KW

Aspecific

IgAresponse

inm

ucosaofim

munized

mice

[Muster

etal.(1995)]

699B

30gp41(720-734

BH

10)gp41(210-224)

HLP

IPR

GP

DR

PE

GIE

mis-folded

LAI

rgp160m

urine(IgG1 )

Donor:

Gearoge

Lewis

References:[A

baciogluetal.(1994)]

NO

TE

S:

•B

30:E

pitopeboundaries

mapped

bypeptide

scanning[A

baciogluetal.(1994)]

700B

31gp41(727-734

BH

10)gp41(217-224)

PD

RP

EG

IEm

is-foldedLA

Irgp160

murine(IgG

1 )

Donor:

Gearoge

Lewis

References:[A

baciogluetal.(1994)]

NO

TE

S:

•B

31:E

pitopeboundaries

mapped

bypeptide

scanning[A

baciogluetal.(1994)]

701B

33gp41(727-734

BH

10)gp41(217-224)

PD

RP

EG

IEN

Baculovirus-

expressedm

is-folded

rgp160IIIB

:NL43,

MicroG

enSys

murine(IgG

1 )

Donor:

Gearoge

Lewis

References:[A

baciogluetal.(1994),B

ristowetal.(1994)]

NO

TE

S:

•B

33:T

hereare

two

MA

bsin

theliterature

named

B33.

See

alsogp120,LA

I123-142[B

ristowetal.(1994)]

•B

33:E

pitopeboundaries

mapped

bypeptide

scanningIgG

1[A

baciogluetal.(1994)]

Page 26: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-231

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

702C

8gp41(727-732

BH

10)gp41(217-222)

PD

RP

EG

Nm

is-foldedLA

Irgp160

murine(IgG

1 )

Donor:

Gearoge

Lewis

References:[P

incus&

McC

lure(1993),Pincus

etal.(1993),Abacioglu

etal.(1994)]N

OT

ES

:•

C8:

Imm

unotoxinof

C8

coupledto

ricin-Adoes

notm

ediatecells

killing,and

isnot

affectedby

sCD

4[P

incus&

McC

lure(1993)]•

C8:

Ab

responsein

IIIBlab

workers

was

compared

togp160

LAI

vaccinerecipients

–C

8w

asused

asa

control–the

dominantresponse

among

vaccineesw

asto

thism

id-gp41region,butnotam

ongthe

infectedlab

workers

–A

bsbinding

thisregion

donotneutralize,bind

toinfected

cells,norserve

asim

munotoxins

[Pincus

etal.(1993)]•

C8:

Epitope

boundariesm

appedby

peptidescanning

[Abacioglu

etal.(1994)]

70388-158/02

gp41(732-752IIIB

)gp41(222-237)

GIE

EE

GG

ER

DR

DR

SIR

rgp41IIIB

murine(IgG

2b )

Donor:

Gearoge

Lewis

References:[N

iedrigetal.(1992a)]

NO

TE

S:

•88-158/02:

Mild

inhibitionofin

vitroactivity

athigh

MA

bconcentrations

–profound

enhancingactivity

atlow

concentrations–

significantreactivityto

virion–

domain

non-imm

unogenicin

humans

[Niedrig

etal.(1992a)]

70488-158/022

gp41(732-752IIIB

)gp41(222-237)

GIE

EE

GG

ER

DR

DR

SIR

rgp41IIIB

murine(IgG

2b )

Donor:

Gearoge

Lewis

References:[N

iedrigetal.(1992a)]

NO

TE

S:

•88-158/022:

Mild

inhibitionofin

vitroactivity

athigh

MA

bconcentrations

–profound

enhancingactivity

atlow

concentrations–

significantreactivityto

virion–

domain

non-imm

unogenicin

humans

[Niedrig

etal.(1992a)]

70588-158/079

gp41(732-752IIIB

)gp41(222-237)

GIE

EE

GG

ER

DR

DR

SIR

rgp41IIIB

murine(IgG

1 )D

onor:G

earogeLew

isR

eferences:[Niedrig

etal.(1992a)]N

OT

ES

:•

88-158/079:M

ildinhibition

ofH

IVin

vitroat

highM

Ab

concentrations–

profoundenhancing

activityat

lowconcentrations

–w

eakbinding

tovirion

–dom

ainnon-im

munogenic

inhum

ans[N

iedrigetal.(1992a)]

Page 27: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-232

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

706B

8gp41(733-741

BH

10)gp41(223-231)

IEE

EG

GE

RD

Nm

is-foldedLA

Irgp160

murine(IgG

1 )

Donor:

Gearoge

Lewis

References:[P

incusetal.(1993),A

baciogluetal.(1994)]

NO

TE

S:

•B

8:A

bresponse

inIIIB

labw

orkersw

ascom

paredto

gp160LA

Ivaccine

recipients–

B8

was

usedas

acontrol–

thedom

inantresponseam

ongvaccinees

was

tothis

mid-gp41

region,butnotamong

theinfected

labw

orkers–

Abs

bindingthis

regiondo

notneutralize,bindto

infectedcells,nor

serveas

imm

unotoxins[P

incusetal.(1993)]

•B

8:E

pitopeboundaries

mapped

bypeptide

scanning[A

baciogluetal.(1994)]

707LA

9(121-

134)gp41(735-752

IIIB)

gp41(218-235)D

RP

EG

IEE

EG

GE

RD

RD

RS

N?

murine(IgM

)

Donor:

Gearoge

Lewis

References:[E

vansetal.(1989)]

708E

D6

gp41(735-752IIIB

)gp41(218-235)

DR

PE

GIE

EE

GG

ER

DR

DR

SN

?m

urine(IgM)

Donor:

Gearoge

Lewis

References:[E

vansetal.(1989)]

7091575

gp41(735-752IIIB

)gp41(218-235)

DR

PE

GIE

EE

GG

ER

DR

DR

SN

Poliovirus/gp41

peptidechim

eram

urine

Donor:

Gearoge

Lewis

References:[E

vansetal.(1989),Vella

etal.(1993),Burattietal.(1997)]

NO

TE

S:

•1575:

Neutralizing

activity,lessbroad

than1577

[Evans

etal.(1989)]•

1575:C

oreepitope:

IEE

E–

neutralizedIIIB

,butnotRF

orM

N[Vella

etal.(1993)]•

1575:S

tudyshow

sthatM

Ab

1575can

recognizethe

IEE

Esequence

inboth

gp41,andin

theH

PG

30region

ofthep17

protein–

motifis

conservedin

bothregions

indifferentH

IV-1

clades[B

urattietal.(1997)]

7101576

gp41(735-752IIIB

)gp41(218-235)

DR

PE

GIE

EE

GG

ER

DR

DR

SN

Poliovirus/gp41

peptidechim

eram

urine

Donor:

Gearoge

Lewis

References:[Vella

etal.(1993)]N

OT

ES

:•

1576:N

otneutralizing[Vella

etal.(1993)]

Page 28: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-233

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

7111577

gp41(735-752IIIB

)gp41(218-235)

DR

PE

GIE

EE

GG

ER

DR

DR

SN

Poliovirus/gp41

peptidechim

eram

urine

Donor:

Morag

Ferguson

(NIB

SC

)R

eferences:[Evans

etal.(1989),D’S

ouzaetal.(1991),Vella

etal.(1993)]N

OT

ES

:•

1577:R

aisedagainstIIIB

peptidechim

era–

neutralizedA

fricanand

Am

ericanH

IV-1

labstrains

[Evans

etal.(1989)]•

1577:N

on-neutralizingin

thism

ulti-labstudy

[D’S

ouzaetal.(1991)]

•1577:

Core

epitope:E

RD

RD

–could

neutralizeH

IVIIIB

andH

IVR

F[Vella

etal.(1993)]•

1577:U

KM

edicalResearch

CouncilA

IDS

reagent:A

RP

317•

1577:N

IHA

IDS

Research

andR

eferenceR

eagentProgram

:1172

7121578

gp41(735-752IIIB

)gp41(218-235)

DR

PE

GIE

EE

GG

ER

DR

DR

SN

Poliovirus/gp41

peptidechim

eram

urine

Donor:

Morag

Ferguson

(NIB

SC

)R

eferences:[Evans

etal.(1989),Vellaetal.(1993)]

NO

TE

S:

•1578:

No

neutralizingactivity

–epitope

may

beform

edby

regionsfrom

bothpoliovirus

andH

IV[E

vansetal.(1989)]

•1578:

Core

epitope:IE

EE

–in

thisstudy,neutralized

IIIB,butnotR

For

MN

[Vellaetal.(1993)]

7131899

gp41(735-752IIIB

)gp41(218-235)

DR

PE

GIE

EE

GG

ER

DR

DR

SN

Poliovirus/gp41

peptidechim

eram

urine

Donor:

Morag

Ferguson

(NIB

SC

)R

eferences:[Vellaetal.(1993)]

NO

TE

S:

•1899:

Could

neutralizeH

IVIIIB

andH

IVR

F[Vella

etal.(1993)]

7141579

gp41(735-752IIIB

)gp41(218-235)

DR

PE

GIE

EE

GG

ER

DR

DR

SN

Poliovirus/gp41

peptidechim

eram

urine

Donor:

Morag

Ferguson

(NIB

SC

)R

eferences:[Vellaetal.(1993)]

NO

TE

S:

•1579:

Core

epitope:IE

EE

–neutralized

IIIB,butnotR

For

MN

[Vellaetal.(1993)]

Page 29: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-234

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

7151583

gp41(735-752IIIB

)gp41(218-235)

DR

PE

GIE

EE

GG

ER

DR

DR

SN

Poliovirus/gp41

peptidechim

eram

urine

Donor:

Morag

Ferguson

(NIB

SC

)R

eferences:[Evans

etal.(1989),Vellaetal.(1993),S

attentauetal.(1995)]

NO

TE

S:

•1583:

Neutralizing

activity,lessbroad

than1577

[Evans

etal.(1989)]•

1583:C

oreepitope:

ER

DR

D–

Could

neutralizeH

IVIIIB

butnotHIV

RF

[Vellaetal.(1993)]

•1583:

Cytoplasm

icdom

ain,epitopenotexposed

atthesurface

ofHIV

-1infected

cells[S

attentauetal.(1995)]

7161907

gp41(735-752IIIB

)gp41(218-235)

DR

PE

GIE

EE

GG

ER

DR

DR

SN

Poliovirus/gp41

peptidechim

eram

urine

Donor:

Morag

Ferguson

(NIB

SC

)R

eferences:[Vellaetal.(1993)]

NO

TE

S:

•1907:

Could

notneutralizeH

IVIIIB

,RF

orM

N[Vella

etal.(1993)]

7171908

gp41(735-752IIIB

)gp41(218-235)

DR

PE

GIE

EE

GG

ER

DR

DR

SN

Poliovirus/gp41

peptidechim

eram

urine

Donor:

Morag

Ferguson

(NIB

SC

)R

eferences:[Evans

etal.(1989),Vellaetal.(1993),S

attentauetal.(1995)]

NO

TE

S:

•1908:

Neutralized

IIIB,butnotR

For

MN

[Vellaetal.(1993)]

•1908:

Cytoplasm

icdom

ain,epitopenotexposed

atthesurface

ofHIV

-1infected

cells[S

attentauetal.(1995)]

7181909

gp41(735-752IIIB

)gp41(218-235)

DR

PE

GIE

EE

GG

ER

DR

DR

SN

Poliovirus/gp41

peptidechim

eram

urine

Donor:

Morag

Ferguson

(NIB

SC

)R

eferences:[Vellaetal.(1993)]

NO

TE

S:

•1909:

Neutralized

HIV

IIIBbutnotH

IVR

F[Vella

etal.(1993)]

71941-1

gp41(735-752IIIB

)gp41(218-235)

DR

PE

GIE

EE

GG

ER

DR

DR

SN

Peptide

735-752IIIB

murine(IgM

κ )

Donor:

Morag

Ferguson

(NIB

SC

)R

eferences:[Dalgleish

etal.(1988)]N

OT

ES

:•

41-1:T

hisantibody

gp41(735-752IIIB

)[D

algleishetal.(1988)]seem

sto

havebeen

named

thesam

eas

adifferent

MA

bto

gp41(584-609)[M

anietal.(1994)]•

41-1:N

eutralizesH

IV-1

butnotHIV

-2strains

[Dalgleish

etal.(1988)]

Page 30: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-235

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

72041-2

gp41(735-752IIIB

)gp41(218-235)

DR

PE

GIE

EE

GG

ER

DR

DR

SN

Peptide

735-752IIIB

murine(IgM

κ )

Donor:

Morag

Ferguson

(NIB

SC

)R

eferences:[Dalgleish

etal.(1988)]N

OT

ES

:•

41-2:N

eutralizesH

IV-1

butnotHIV

-2strains

[Dalgleish

etal.(1988)]

72141-3

gp41(735-752IIIB

)gp41(218-235)

DR

PE

GIE

EE

GG

ER

DR

DR

SN

Peptide

735-752IIIB

murine(IgM

κ )

Donor:

Morag

Ferguson

(NIB

SC

)R

eferences:[Dalgleish

etal.(1988)]N

OT

ES

:•

41-3:N

eutralizesH

IV-1

butnotHIV

-2strains

[Dalgleish

etal.(1988)]

7224E

10gp41(824-830

BH

10)gp41(313-319)

AE

GT

DR

VN

HIV

-1infection

human(IgG

3κ )

Donor:

Morag

Ferguson

(NIB

SC

)R

eferences:[Buchacher

etal.(1992),Buchacher

etal.(1994),D’S

ouzaetal.(1994)]

NO

TE

S:

•4E

10:M

Abs

generatedby

electrofusionofP

BL

fromH

IV-1+

volunteersw

ithC

B-F

7cells

–also

bindsto

MH

Cclass

IIproteins–

anti-classIIA

bsare

onlyfound

inH

IV-1

positivepeople

[Buchacher

etal.(1994)]•

4E10:

Includedin

am

ulti-labstudy

forantibody

characterization,binding

andneutralization

assaycom

parison[D

’Souza

etal.(1994)]

723D

Zgp41(827-860

BR

U)

gp41(312-345)VA

EG

TD

RV

IEV

VQ

GA

CR

-A

IRH

IPR

RIR

QG

LER

IL?L

recvaccinia

gp160IIIB

human(IgG

1λ )

Donor:

?R

eferences:[Boyer

etal.(1991)]N

OT

ES

:•

DZ

:Weakly

neutralizingIIIB

–binds

topeptides

827-843and

846-860ofB

RU

–reacted

specificallyw

ithIIIB

andR

F[B

oyeretal.(1991)]

724C

hessie8

gp41(cytoplasmic

domain)

gp41VA

EG

TD

RV

IEV

VQ

GA

CR

-A

IRH

IPR

RIR

QG

LER

IL?m

urine(IgG)

Donor:

G.Lew

isR

eferences:[Lewis

etal.(1991),Poum

bouriosetal.(1995),R

ovinskietal.(1995)]N

OT

ES

:•

Chessie

8:U

sedto

precipitategp160

inim

munoblots

ina

studyexam

iningthe

feasibilityofusing

unprocessedgp160

glycoproteinas

anim

munogen

[Rovinskietal.(1995)]

Page 31: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-236

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

725K

14gp41(dis)

gp41(dis)D

ISC

ON

TIN

UO

US

Nhum

an(IgG1 )

Donor:

?R

eferences:[Teeuwsen

etal.(1990),

Schutten

etal.(1995a),

Schutten

etal.(1995b),

Schutten

etal.(1996),

Schutten

etal.(1997)]N

OT

ES

:•

K14:

Did

notbindto

peptidesspanning

gp41,butitdoesnotreactw

ithenv

deletionm

utant643-692–

doesnotreact

with

HIV

-2–

competition

experiments

showed

thisw

asan

imm

unodominant

conservedepitope

inH

IV-1

positivesera

fromE

uropeand

Africa

[Teeuwsen

etal.(1990)]•

K14:

Reduced

affinityfor

bothS

IandN

SIviruses

relativeto

MA

bM

N215,failed

toneutralize

SIstrain

[Schutten

etal.(1995b)]•

K14:

Ina

studyofN

SIand

SIvirus

neutralization,K14

didnotinfluence

viralentry[S

chuttenetal.(1997)]

726T

30gp41(dis)

gp41(dis)D

ISC

ON

TIN

UO

US

Ntetram

ericE

nvm

urineD

onor:?

References:[E

arletal.(1994),Earletal.(1997)]

NO

TE

S:

•T

30:binds

tothe

region580

to640,butdoes

notbindto

peptidesspanning

thisregion

–binding

dependson

N-linked

glycosylationofA

sn616

–no

otherantibody

testedinhibited

binding,butbinding

couldbe

inhibitedby

serafrom

HIV

+individuals

[Earletal.(1997)]

727126-50

gp41(disH

XB

2)gp41(dis)

DIS

CO

NT

INU

OU

SN

HIV

-1infection

human(IgG

2κ )

Donor:

?R

eferences:[Robinson

Jr.etal.(1990a),Tyler

etal.(1990),Robinson

Jr.etal.(1991),X

uetal.(1991)]

NO

TE

S:

•126-50:

No

enhancingactivity

forH

IV-1

IIIB[R

obinsonJr.

etal.(1990a)]•

126-50:S

ervesas

targetforantibody-dependentcellular

cytotoxicityA

DC

C[Tyler

etal.(1990)]•

126-50:N

oenhancing

orneutralizing

activity[R

obinsonJr.

etal.(1991)]•

126-50:S

pecificfor

aconform

ationalepitope[X

uetal.(1991)]

Page 32: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-237

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

728T

4gp41(dis

IIIB)

gp41(dis)D

ISC

ON

TIN

UO

US

Lvaccinia

expressedoligom

ericgp140

IIIB

murine(IgG

)

Donor:

?R

eferences:[Earletal.(1994),B

roderetal.(1994),Richardson

Jretal.(1996),Weissenhorn

etal.(1996),Earletal.(1997),

Otteken

etal.(1996)]N

OT

ES

:•

T4:

oneof

fiveM

Abs

(T4,

T6,

T9,

T10

andT

35)in

acom

petitiongroup

thatbind

toa

conformation-dependent

epitopein

gp41and

isoligom

erspecific

–neutralizes

IIIBand

SF

2[B

roderetal.(1994)]

•T

4:D

oesnotbind

tosoluble

monom

ericgp41(21-166)

thatlacksthe

fusionpeptide

andm

embrane

anchor,onlyto

theoligom

ergp140,as

doesT

6[W

eissenhornetal.(1996)]

•T

4:T

hisantibody,

alongw

ith7

others(M

10,D

41,D

54,T

6,T

9,T

10and

T35),

canblock

thelinear

murine

MA

bD

61,andthe

human

MA

b246-D

,which

bothbind

tothe

imm

unodominantregion

nearthe

two

Cys

ingp41

–m

ostofthese

antibodiesare

oligomerdependent–

alloftheM

Abs

arereactive

with

tendifferentH

IV-1

strains–

mem

bersofthis

competition

groupare

blockedby

serafrom

HIV

-1+individuals

[Earletal.(1997)]

•M

Abs

T4

andT

6bind

onlyto

oligomer,and

pulsechase

experiments

indicatethatthe

epitopeis

veryslow

toform

,requiring

oneto

two

hours[O

ttekenetal.(1996)]

729D

12gp41(dis

IIIB)

gp41(dis)D

ISC

ON

TIN

UO

US

Lvaccinia

expressedoligom

ericgp140

IIIB

murine(IgG

)

Donor:

?R

eferences:[Broder

etal.(1994),Richardson

Jretal.(1996),E

arletal.(1997),Otteken

etal.(1996)]N

OT

ES

:•

D12:

One

of18

MA

bs(e.

g.D

4and

D40)

thatbind

toa

conformation-dependent

epitopein

gp41that

bindpreferentially,butnotexclusively,to

oligomers

–neutralizes

IIIBand

SF

2[B

roderetal.(1994)]

•D

12:T

hisantibody

was

blockedm

orestrongly

byhum

ansera

thanother

anti-gp41M

Abs

(D20,D

43,D61,and

T4)

ina

oligomeric

ELIS

Aassay

[Richardson

Jretal.(1996)]

•D

12:M

Abs

D10

andD

12are

veryeasily

blockedby

human

serafrom

HIV

+individuals

[Earletal.(1997)]

•D

12:M

Abs

D4,

D10,

D11,

D12,

andD

41allbind

onlyto

complete

oligomer

–pulse

labelexperiments

ofM

Ab

bindingto

noncleavablegp160

revealedthatthese

MA

bsbound

with

adelay,epitopes

forming

with

ahalflife

of30m

in[O

ttekenetal.(1996)]

Page 33: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-238

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

730D

1gp41(dis

IIIB)

gp41(dis)D

ISC

ON

TIN

UO

US

vacciniaexpressed

oligomeric

gp140IIIB

murine(IgG

)

Donor:

?R

eferences:[Otteken

etal.(1996)]N

OT

ES

:•

D1:

MA

bsD

1,D

16,had

T37

bindto

oligomeric

gp160equally

well–

pulselabelexperim

entsof

MA

bbinding

tononcleavable

gp160revealed

thatthese

MA

bsbound

with

adelay,

epitopesform

ingw

itha

halflife

of30

min

[Otteken

etal.(1996)]

731D

16gp41(dis

IIIB)

gp41(dis)D

ISC

ON

TIN

UO

US

Ldim

ericE

nvm

urine(IgG)

Donor:

?R

eferences:[Earletal.(1994),W

eissenhornetal.(1996),E

arletal.(1997)]N

OT

ES

:•

D16:

Precipitates

botholigom

ericgp140

andsoluble

monom

ericgp41(21-166)that

lacksthe

fusionpeptide

andm

embrane

anchor,alongw

ithM

Abs

D16,D

38,D40,D

41,andD

54[W

eissenhornetal.(1996)]

•D

16:O

neofeleven

MA

bs(D

16,D17,D

31,D36,D

37,D40,D

44,D55,D

59,T37,and

T45)

thatareconform

ationdependentand

thatcanblock

thebinding

oftheM

Ab

D50

thatbindsto

thelinear

peptidegp41(642-665)

–reactive

with

9/10H

IV-1

strainsallexceptH

IV-1

AD

A,w

hichhas

thechange

E659D

andE

662Athatm

ayresultin

theloss

ofbinding(E

LLEto

DLLA

)[E

arletal.(1997)]

732126-6

gp41(disH

XB

2)gp41(dis)

DIS

CO

NT

INU

OU

SN

HIV

-1infection

human(IgG

2κ )

Donor:

Susan

Zolla-P

azner,NY

UM

edC

enter,NY,N

YR

eferences:[Robinson

Jr.et

al.(1990a),R

obinsonJr.

etal.(1991),

Xu

etal.(1991),

Eddleston

etal.(1993),

Chen

etal.(1995),Binley

etal.(1996),Earletal.(1997)]

NO

TE

S:

•126-6:

No

enhancingactivity

forH

IV-1

IIIB[R

obinsonJr.

etal.(1990a)]•

126-6:N

oenhancing

orneutralizing

activity[R

obinsonJr.

etal.(1991)]•

126-6:S

pecificfor

aconform

ationalepitope[X

uetal.(1991)]

•126-6:

Called

SZ

-126.6[E

ddlestonetal.(1993)]

•126-6:

One

ofseveral

anti-gp41M

Abs

thatbind

toa

gp41-maltose

bindingfusion

proteindesigned

tostudy

theleucine

zipperdom

ainofgp41,show

ingthatthe

constructhasretained

aspectsofnorm

algp41conform

ation[C

henetal.(1995)]

•126-6:

Discontinuous

epitoperecognizing

residuesbetw

een649-668

–designated

clusterII

–F

absD

5,D

11,G

1,T

3,M12,M

15,S6,S

8,S9,S

10block

binding[B

inleyetal.(1996)]

•126-6:

NIH

AID

SR

esearchand

Reference

ReagentP

rogram:

1243

Page 34: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-239

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

733D

43gp41(dis

HX

B2)

gp41(dis)D

ISC

ON

TIN

UO

US

dimeric

Env

murine(IgG

)D

onor:S

usanZ

olla-Pazner,N

YU

Med

Center,N

Y,NY

References:[E

arletal.(1994),Richardson

Jretal.(1996),E

arletal.(1997)]N

OT

ES

:•

D43:

This

isa

lineargp41

epitope,m

appingin

theregion

635-678–

human

serablocked

bindingin

oligomeric

ELIS

Aassay

toa

similar

extentforgp41

MA

bsD

20,D43,D

61,andT

4[R

ichardsonJr

etal.(1996)]•

D43:

Partially

conformation

dependent–doesn’tbind

toshortpeptides,butdoes

bindto

theregion

spanning641-683

–binding

canbe

blockedby

MA

bsT

3,D

38and

D45

–M

Abs

inthis

competition

groupreacted

with

9/10H

IV-1

strains,notbindingto

JRF

L[E

arletal.(1997)]

734T

3gp41(dis

HX

B2)

gp41(dis)D

ISC

ON

TIN

UO

US

tetrameric

Env

murine(IgG

)D

onor:S

usanZ

olla-Pazner,N

YU

Med

Center,N

Y,NY

References:[E

arletal.(1994),Earletal.(1997)]

NO

TE

S:

•T

3:P

artiallyconform

ationdependent–

doesn’tbindto

shortpeptides,butdoesbind

tothe

regionspanning

641-683–

bindingcan

beblocked

byM

Abs

D43,

D38

andD

45–

MA

bsin

thiscom

petitiongroup

reactedw

ith9/10

HIV

-1strains,notbinding

toJR

FL

[Earletal.(1997)]

735M

d-1gp41(dis)

gp41(dis)D

ISC

ON

TIN

UO

US

N?

human(IgG

1λ )

Donor:

R.A

.Myers

State

ofMaryland

Dept.

ofHealth

References:[M

yersetal.(1993),C

henetal.(1995),B

inleyetal.(1996)]

NO

TE

S:

•M

d-1:A

lsocalled

MD

-1•

Md-1:

Called

MD

-1–

discontinuousepitope

thatbindsin

theN

-terminalregion

–reacts

exclusivelyw

itholigom

er[M

yersetal.(1993)]

•M

d-1:C

alledM

D-1

–one

ofseveralanti-gp41M

Abs

thatbindto

agp41-m

altosebinding

fusionprotein

designedto

studythe

leucinezipperdom

ainofgp41,show

ingthatthe

constructhasretained

aspectsofnorm

algp41conform

ation[C

henetal.(1995)]

•M

d-1:D

iscontinuousepitope

recognizingresidues

between

563-672,does

notrecognize

clusterI

disulfidebridge

region–

reactsalm

ostexclusivelyw

ithtrim

ersand

tetramers

onW

B–

designatedcluster

II–F

absD

5,D11,G

1,T3,

M12,M

15,S6,S

8,S9,S

10block

binding[B

inleyetal.(1996)]

•M

d-1:N

IHA

IDS

Research

andR

eferenceR

eagentProgram

:1223

Page 35: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-240

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

736F

abD

5gp41(dis

LAI)

gp41(dis)D

ISC

ON

TIN

UO

US

NH

IV-1

infectionhum

an(IgG1κ )

Donor:

R.A

.Myers

State

ofMaryland

Dept.

ofHealth

References:[B

inleyetal.(1996)]

NO

TE

S:

•F

abD

5:B

indsto

Cluster

IIregion–

competes

with

MA

bs126-6,M

d-1and

D50

–conform

ationsensitive

–variable

regionssequenced

[Binley

etal.(1996)]

737F

abD

11gp41(dis

LAI)

gp41(dis)D

ISC

ON

TIN

UO

US

NH

IV-1

infectionhum

an(IgG1κ )

Donor:

R.A

.Myers

State

ofMaryland

Dept.

ofHealth

References:[B

inleyetal.(1996)]

NO

TE

S:

•F

abD

11:B

indsto

ClusterIIregion

–com

petesw

ithM

Abs

126-6,Md-1

andD

50–

conformation

sensitive–

variableregions

sequenced[B

inleyetal.(1996)]

738F

abG

1gp41(dis

LAI)

gp41(dis)D

ISC

ON

TIN

UO

US

NH

IV-1

infectionhum

an(IgG1κ )

Donor:

R.A

.Myers

State

ofMaryland

Dept.

ofHealth

References:[B

inleyetal.(1996)]

NO

TE

S:

•F

abG

1:B

indsto

Cluster

IIregion–

competes

with

MA

bs126-6,M

d-1and

D50

–conform

ationsensitive

–variable

regionssequenced

[Binley

etal.(1996)]

739F

abT

3gp41(dis

LAI)

gp41(dis)D

ISC

ON

TIN

UO

US

NH

IV-1

infectionhum

an(IgG1κ )

Donor:

R.A

.Myers

State

ofMaryland

Dept.

ofHealth

References:[B

inleyetal.(1996)]

NO

TE

S:

•F

abT

3:B

indsto

Cluster

IIregion–

competes

with

MA

bs126-6,M

d-1and

D50

–conform

ationsensitive

–variable

regionssequenced

[Binley

etal.(1996)]

740F

abM

10gp41(dis

LAI)

gp41(dis)D

ISC

ON

TIN

UO

US

NH

IV-1

infectionhum

an(IgG1κ )

Donor:

R.A

.Myers

State

ofMaryland

Dept.

ofHealth

References:[B

inleyetal.(1996),P

arrenetal.(1997b)]

NO

TE

S:

•F

abM

10:B

indsto

ClusterIIregion

–com

petesw

ithM

Abs

126-6,Md-1

andD

50–

conformation

sensitive–

variableregions

sequenced[B

inleyetal.(1996)]

•F

abM

10:D

oesnot

bindto

MN

nativeoligom

er,but

doesbind

toboth

LAI

andM

Nrgp120

andrgp140

[Parren

etal.(1997b)]

Page 36: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-241

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

741F

abM

12gp41(dis

LAI)

gp41(dis)D

ISC

ON

TIN

UO

US

NH

IV-1

infectionhum

an(IgG1κ )

Donor:

R.A

.Myers

State

ofMaryland

Dept.

ofHealth

References:[B

inleyetal.(1996)]

NO

TE

S:

•F

abM

12:B

indsto

ClusterIIregion

–com

petesw

ithM

Abs

126-6,Md-1

andD

50–

conformation

sensitive–

variableregions

sequenced[B

inleyetal.(1996)]

742F

abM

15gp41(dis

LAI)

gp41(dis)D

ISC

ON

TIN

UO

US

NH

IV-1

infectionhum

an(IgG1κ )

Donor:

R.A

.Myers

State

ofMaryland

Dept.

ofHealth

References:[B

inleyetal.(1996)]

NO

TE

S:

•F

abM

15:B

indsto

ClusterIIregion

–com

petesw

ithM

Abs

126-6,Md-1

andD

50–

conformation

sensitive–

variableregions

sequenced[B

inleyetal.(1996)]

743F

abS

6gp41(dis

LAI)

gp41(dis)D

ISC

ON

TIN

UO

US

NH

IV-1

infectionhum

an(IgG1κ )

Donor:

R.A

.Myers

State

ofMaryland

Dept.

ofHealth

References:[B

inleyetal.(1996)]

NO

TE

S:

•F

abS

6:B

indsto

Cluster

IIregion–

competes

with

MA

bs126-6,M

d-1and

D50

–conform

ationsensitive

–variable

regionssequenced

[Binley

etal.(1996)]

744F

abS

8gp41(dis

LAI)

gp41(dis)D

ISC

ON

TIN

UO

US

NH

IV-1

infectionhum

an(IgG1κ )

Donor:

R.A

.Myers

State

ofMaryland

Dept.

ofHealth

References:[B

inleyetal.(1996)]

NO

TE

S:

•F

abS

8:B

indsto

Cluster

IIregion–

competes

with

MA

bs126-6,M

d-1and

D50

–conform

ationsensitive

–variable

regionssequenced

[Binley

etal.(1996)]

745F

abS

9gp41(dis

LAI)

gp41(dis)D

ISC

ON

TIN

UO

US

NH

IV-1

infectionhum

an(IgG1κ )

Donor:

R.A

.Myers

State

ofMaryland

Dept.

ofHealth

References:[B

inleyetal.(1996)]

NO

TE

S:

•F

abS

9:B

indsto

Cluster

IIregion–

competes

with

MA

bs126-6,M

d-1and

D50

–conform

ationsensitive

–variable

regionssequenced

[Binley

etal.(1996)]

Page 37: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-242

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

746F

abS

10gp41(dis

LAI)

gp41(dis)D

ISC

ON

TIN

UO

US

NH

IV-1

infectionhum

an(IgG1κ )

Donor:

R.A

.Myers

State

ofMaryland

Dept.

ofHealth

References:[B

inleyetal.(1996)]

NO

TE

S:

•F

abS

10:B

indsto

ClusterIIregion

–com

petesw

ithM

Abs

126-6,Md-1

andD

50–

conformation

sensitive–

variableregions

sequenced[B

inleyetal.(1996)]

747F

abL2

gp41(disLA

I)gp41(dis)

DIS

CO

NT

INU

OU

SN

HIV

-1infection

human(IgG

1κ )

Donor:

P.Perrin

andD

.Burton

(Scripps

Research

Institute,LaJolla,C

aliforniaR

eferences:[Binley

etal.(1996),Earletal.(1997)]

NO

TE

S:

•F

abL2:

Binds

toC

lusterIII

region–

competes

with

MA

bM

d-1,but

notM

Abs

126-6and

D50

–conform

ationsensitive

–variable

regionssequenced

[Binley

etal.(1996)]

748F

abL11

gp41(disLA

I)gp41(dis)

DIS

CO

NT

INU

OU

SN

HIV

-1infection

human(IgG

1κ )

Donor:

P.Perrin

andD

.Burton

(Scripps

Research

Institute,LaJolla,C

aliforniaR

eferences:[Binley

etal.(1996)]N

OT

ES

:•

Fab

L11:B

indsto

Cluster

IIIregion

–com

petesw

ithM

Ab

Md-1,

butnot

MA

bs126-6

andD

50–

conformation

sensitive–

variableregions

sequenced[B

inleyetal.(1996)]

749F

abL1

gp41(disLA

I)gp41(dis)

DIS

CO

NT

INU

OU

SN

HIV

-1infection

human(IgG

1κ )

Donor:

P.Perrin

andD

.Burton

(Scripps

Research

Institute,LaJolla,C

aliforniaR

eferences:[Binley

etal.(1996)]N

OT

ES

:•

Fab

L1:B

indsto

Cluster

IIIregion

–com

petesw

ithM

Ab

Md-1,

butnot

MA

bs126-6

andD

50–

conformation

sensitive–

variableregions

sequenced[B

inleyetal.(1996)]

750F

abG

5gp41(dis

LAI)

gp41(dis)D

ISC

ON

TIN

UO

US

NH

IV-1

infectionhum

an(IgG1κ )

Donor:

P.Perrin

andD

.Burton

(Scripps

Research

Institute,LaJolla,C

aliforniaR

eferences:[Binley

etal.(1996)]N

OT

ES

:•

Fab

G5:

Binds

toC

lusterIII

region–

competes

with

MA

bM

d-1,but

notM

Abs

126-6and

D50

–conform

ationsensitive

–variable

regionssequenced

[Binley

etal.(1996)]

Page 38: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-243

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

751F

abG

15gp41(dis

LAI)

gp41(dis)D

ISC

ON

TIN

UO

US

NH

IV-1

infectionhum

an(IgG1κ )

Donor:

P.Perrin

andD

.Burton

(Scripps

Research

Institute,LaJolla,C

aliforniaR

eferences:[Binley

etal.(1996)]N

OT

ES

:•

Fab

G15:

Binds

toC

lusterIII

region–

competes

with

MA

bM

d-1,but

notM

Abs

126-6and

D50

–conform

ationsensitive

–variable

regionssequenced

[Binley

etal.(1996)]

752F

abA

9gp41(dis

LAI)

gp41(dis)D

ISC

ON

TIN

UO

US

NH

IV-1

infectionhum

an(IgG1κ )

Donor:

P.Perrin

andD

.Burton

(Scripps

Research

Institute,LaJolla,C

aliforniaR

eferences:[Binley

etal.(1996)]N

OT

ES

:•

Fab

A9:

Binds

toC

lusterIII

region–

competes

with

MA

bM

d-1,but

notM

Abs

126-6and

D50

–conform

ationsensitive

–variable

regionssequenced

[Binley

etal.(1996)]

753F

abA

12gp41(dis

LAI)

gp41(dis)D

ISC

ON

TIN

UO

US

NH

IV-1

infectionhum

an(IgG1κ )

Donor:

P.Perrin

andD

.Burton

(Scripps

Research

Institute,LaJolla,C

aliforniaR

eferences:[Binley

etal.(1996)]N

OT

ES

:•

Fab

A12:

Uncharacterized

epitope–

variableregions

sequenced[B

inleyetal.(1996)]

754F

abL9

gp41(disLA

I)gp41(dis)

DIS

CO

NT

INU

OU

SN

HIV

-1infection

human(IgG

1κ )

Donor:

P.Perrin

andD

.Burton

(Scripps

Research

Institute,LaJolla,C

aliforniaR

eferences:[Binley

etal.(1996)]N

OT

ES

:•

Fab

L9:U

ncharacterizedepitope

–variable

regionssequenced

[Binley

etal.(1996)]

755F

abA

2gp41(dis

LAI)

gp41(dis)D

ISC

ON

TIN

UO

US

NH

IV-1

infectionhum

an(IgG1λ )

Donor:

P.Perrin

andD

.Burton

(Scripps

Research

Institute,LaJolla,C

aliforniaR

eferences:[Binley

etal.(1996)]N

OT

ES

:•

Fab

A2:

Uncharacterized

epitope–

variableregions

sequenced[B

inleyetal.(1996)]

756H

2gp41(dis)

gp41(dis)D

ISC

ON

TIN

UO

US

?hum

an(IgMκ )

Donor:

BioInvent,Lund,S

weden,com

mercial

References:[M

ulleretal.(1991)]

NO

TE

S:

•H

2:A

nti-idiotypicM

Abs

(10B3

and2A

ll)againstH

2w

eregenerated

byim

munization

ofBA

LB/c

mice

with

H2

–they

alsoreactw

ithseropositive

sera[M

ulleretal.(1991)]

Page 39: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-244

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

757M

O43

gp41(dis)gp41(dis)

DIS

CO

NT

INU

OU

SN

invitro

rE

nvpenv9

human(IgM

)

Donor:

?R

eferences:[Ohlin

etal.(1989)]N

OT

ES

:•

MO

43:D

iscontinuousepitope

involvinghydrophobic

regions632-646,

677-681and

687-691,proxim

alto

andspanning

thetransm

embrane

region–

thisspecificity

isunusualin

HIV

-1positive

sera[O

hlinetal.(1989)]

758M

O30

gp41(dis)gp41(dis)

DIS

CO

NT

INU

OU

SN

invitro

rE

nvpenv9

human(IgM

)

Donor:

?R

eferences:[Ohlin

etal.(1989)]N

OT

ES

:•

MO

30:D

iscontinuousepitope

involvinghydrophobic

regions632-646,

677-681and

687-691,proxim

alto

andspanning

thetransm

embrane

region–

thisspecificity

isunusualin

HIV

-1positive

sera[O

hlinetal.(1989)]

759M

O28

gp41(dis)gp41(dis)

DIS

CO

NT

INU

OU

SN

invitro

rE

nvpenv9

human(IgM

)

Donor:

?R

eferences:[Ohlin

etal.(1989)]N

OT

ES

:•

MO

28:D

iscontinuousepitope

involvinghydrophobic

regions632-646,

677-681and

687-691,proxim

alto

andspanning

thetransm

embrane

region–

thisspecificity

isunusualin

HIV

-1positive

sera[O

hlinetal.(1989)]

7602A

2gp41(N

-term)

gp41(dis)?

NH

IV-1

infectionhum

an(IgG1κ )

Donor:

?R

eferences:[Weissenhorn

etal.(1996)]N

OT

ES

:•

Soluble

gp41(21-166)form

sa

rodlike

structurethatcan

bevisualized

with

electronm

icroscopy,and

2A2

bindsto

oneend

oftherod

[Weissenhorn

etal.(1996)]

Page 40: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-245

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

761N

2-4gp41

gp41?

NH

IV-1

infectionhum

an(IgG1κ )

Donor:

Evan

Hersh

andYoh-IchiM

atsumoto

References:[R

obinsonJr.

etal.(1990a)]N

OT

ES

:•

N2-4:

No

enhancingactivity

forH

IV-1

IIIB[R

obinsonJr.

etal.(1990a)]•

N2-4:

NIH

AID

SR

esearchand

Reference

ReagentP

rogram:

528

762M

25gp41

gp41?

purifiedH

TLV

-IIIm

urine(IgGκ )D

onor:E

vanH

ershand

Yoh-IchiMatsum

otoR

eferences:[diMarzo

Veroneseetal.(1985),W

atkinsetal.(1996)]

NO

TE

S:

•M

25:heavy

andlight

chainscloned

andsequenced

–binding

requiresheavy

andlight

chainin

combination,

incontrastto

M77

[Watkins

etal.(1996)]

76310E

9gp41

gp41?

HIV

-1infection

murine(IgG

1 )D

onor:E

vanH

ershand

Yoh-IchiMatsum

otoR

eferences:[Papsidero

etal.(1988)]N

OT

ES

:•

10E9:

100/100H

IV+

human

seracould

inhibit10E9

binding[P

apsideroetal.(1988)]

76431A

1gp41

gp41?

Nin

vitroim

muniza-

tion,denatured

HIV

-1

human(IgM

κ/λ )

Donor:

?R

eferences:[Pollock

etal.(1989)]N

OT

ES

:•

31A1:

Reacts

with

bothp24

andgp41

[Pollock

etal.(1989)]

76539A

64gp41

gp41?

Nin

vitroim

muniza-

tion,denatured

HIV

-1

human(IgM

κ/λ )

Donor:

?R

eferences:[Pollock

etal.(1989)]N

OT

ES

:•

39A64:

Reacts

with

bothp24

andgp41

[Pollock

etal.(1989)]

Page 41: HIV Monoclonal Antibodies...25C2: Human MAb generated by electrofusion of PBL from HIV-1+ volunteers with CB-F7 cells – binds oligomeric and monomeric gp41, and gp160 [Buchacher

HIV

MonoclonalA

ntibodies

III-A-246

DE

C98

MA

bID

LocationW

EA

US

equenceN

eutralizingIm

munogen

Species(Isotype)

76639B

86gp41

gp41?

Nin

vitroim

muniza-

tion,denatured

HIV

-1

human(IgM

κ/λ )

Donor:

?R

eferences:[Pollock

etal.(1989)]N

OT

ES

:•

39B86:

Reacts

with

bothp24

andgp41

[Pollock

etal.(1989)]

7679303

gp41gp41

Nm

urineD

onor:D

uP

ontR

eferences:[McD

ougaletal.(1996)]

7683H

6gp41

gp41m

urineD

onor:D

uP

ontR

eferences:[Pinter

etal.(1995)]N

OT

ES

:•

3H6:

There

isanother

MA

bw

iththis

IDthatrecognizes

Rev

[Orsinietal.(1995)]

•3H

6:G

eneratedin

responseto

virusgrow

nin

protein-freem

edium[P

interetal.(1995)]

76931710B

gp41gp41

human(IgG

1)D

onor:D

uP

ontR

eferences:[Alsm

adi&T

illey(1998)]N

OT

ES

:•

31710B:A

studyof6

anti-Env

MA

bsand

theirability

tobind

ordirectA

DC

Cagainsttargetcells

infectedw

ithIIIB

,M

N,S

F-2,and

RF

–bound

anddirected

lysisagainstallfour

strains[A

lsmadi&

Tilley(1998)]