SFC/10 6 PBMC BCG PPD-specific IFN-γ ELISpot Responses rBCGrAd5rBCG Median Weeks after immunization...
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0 10 20 30 40 50 60 0 1000 2000 3000 4000 5000 rBCG IV rBCG IM rBCG ID C ontrol SFC/10 6 PBMC BCG PPD-specific IFN-γ ELISpot Responses rBCG rAd5 rBCG Median Weeks after immunization Figure #1
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Transcript of SFC/10 6 PBMC BCG PPD-specific IFN-γ ELISpot Responses rBCGrAd5rBCG Median Weeks after immunization...
0 10 20 30 40 50 600
1000
2000
3000
4000
5000rBCG IVrBCG IMrBCG IDControl
SF
C/1
06 P
BM
C
BCG PPD-specific IFN-γ ELISpot Responses
rBCG rAd5rBCG
Median
Weeks after immunization
Figure #1
SF
C/1
06 P
BM
C
SIV-specific IFN-γ ELISpot Responses
Median
c. Pol peptide pool stimulated
0 10 20 30 40 50 600
1000
2000
3000
4000
BCG IVBCG IDBCG IMControl
0 10 20 30 40 50 600
500
1000
1500
2000
2500
rBCG rAd5rBCG
a. Gag peptide pool stimulated b. p11C peptide stimulated
d. Env peptide pool stimulated
0 10 20 30 40 50 600
1000
2000
3000
4000
0 10 20 30 40 50 600
500
1000
1500
2000
2500
Weeks after immunization
Figure #2
% T
etra
mer
bin
din
g
CD
8+ T
cel
ls
0.0
0.5
1.0
1.5
2.0
203-06
211-06
157-06
212-06
150-06
206-06
149-06
205-06
159-06
213-06
160-06
208-06
158-06
210-06
152-06
207-06
204-06
214-06
10^6→10^9
10^9 10^8 10^7 10^6 10^9 10^8 10^7 10^6
ID IM IV
pre
wk 4
wk 27
SIV-specific CD8+ T-cell Responses after In Vitro Culture Stimulation of PBMC
with p11C Peptide and Interleukin-2
Monkey
rBCG dose (cfu)
Route
Figure #3
10^9
-10^
6 ID
10^9
IV
10^8
IV
10^7
IV
10^6
IV
Control
0
1000
2000
3000
4000
5000
10^9-
10^6
ID
10^9
IV
10^8
IV
10^7
IV
10^6
IV
Control
0
1000
2000
3000
4000
5000
10^9-
10^6
ID
10^9
IV
10^8
IV
10^7
IV
10^6
IV
Control
0
1000
2000
3000
4000
5000
10^9
-10^
6 ID
10^9
IV
10^8
IV
10^7
IV
10^6
IV
Control
0
1000
2000
3000
4000
5000
2 weeks after rAd5 4 weeks after rAd5
10 weeks after rAd5 21 weeks after rAd5
SIV Gag-specific IFN-γ ELISpot Responses by Dosage
SF
C/1
06 P
BM
C
Figure #4a
10^9
IV
10^8
IV
10^7
IV
10^6
IV
Control
0
1000
2000
3000
4000
5000
2 weeks after rAd5 4 weeks after rAd5
10 weeks after rAd5 21 weeks after rAd5
SIV Pol-specific IFNγ ELISpot Responses by Dosage
10^9
-10^
6 ID
10^9
IV
10^8
IV
10^7
IV
10^6
IV
Control
0
1000
2000
3000
4000
5000
10^9-
10^6
ID
10^9
IV
10^8
IV
10^7
IV
10^6
IV
Control
0
1000
2000
3000
4000
5000
10^9
-10^
6 ID
10^9
IV
10^8
IV
10^7
IV
10^6
IV
Control
0
1000
2000
3000
4000
5000
SF
C/1
06 P
BM
C
Figure #4b
2 weeks after rAd5 4 weeks after rAd5
SIV Gag-specific IFNγ ELISpot Responses by RouteS
FC
/106
PB
MC
* Mann-Whitney Test
Kruskall-Wallis Test: p=0.0079;Dunn's Multiple Comparison (adjusted for multiple comparison):p<0.05 for BCG IV vs. Control: significantp<0.05 for BCG ID vs. Control: significantp>0.05 for all other group comparisons
* Mann-Whitney Test
Kruskall-Wallis Test: p=0.0780;Dunn's Multiple Comparison (adjusted for multiple comparison):p>0.05 between all groups
rBCG IV
rBCG ID
rBCG IM
Control
0
1000
2000
3000
4000
5000
p=0.0499*
p=0.0242*
p=0.0242*
rBCG IV
rBCG ID
rBCG IM
Control
0
1000
2000
3000
4000
5000
p=0.0499*
p=0.1939*
p=0.9212*
Figure #5a
10 weeks after rAd5 21 weeks after rAd5
SIV Gag-specific IFN-γ ELISpot Responses by RouteS
FC
/106
PB
MC
* Mann-Whitney Test
Kruskall-Wallis Test: p=0.0406;Dunn's Multiple Comparison (adjusted for multiple comparison):p>0.05 between all groups
* Mann-Whitney Test
Kruskall-Wallis Test: p=0.0227;Dunn's Multiple Comparison (adjusted for multiple comparison):p<0.05 for ID vs. Control,p>0.05 for all other group comparisons
rBCG IV
rBCG ID
rBCG IM
Control
0
1000
2000
3000
4000
5000
p=0.0379*
p=0.0485*
p=0.7758*
rBCG IV
rBCG ID
rBCG IM
Control
0
1000
2000
3000
4000
5000
p=0.0830*
p=0.0848*
p=0.1836*
Figure #5b
2 weeks after rAd5 4 weeks after rAd5
SIV Pol-specific IFN-γ ELISpot Responses by RouteS
FC
/106
PB
MC
* Mann-Whitney Test
Kruskall-Wallis Test: p=0.0146;Dunn's Multiple Comparison (adjusted for multiple comparison):p<0.05 for BCG IV vs. Control: significantp>0.05 for all other group comparisons
* Mann-Whitney Test
Kruskall-Wallis-Test: p= 0.2101;Dunn's Multiple Comparison (adjusted for multiple comparison):p>0.05 between all groups
rBCG IV
rBCG ID
rBCG IM
Control
0
1000
2000
3000
4000
5000
p=0.0499*
p=0.0242*
p=0.0485*
rBCG IV
rBCG ID
rBCG IM
Control
0
1000
2000
3000
4000
5000
p=0.3717*
p=0.2605*
p=0.7758*
Figure #5c
10 weeks after rAd5 21 weeks after rAd5
SIV Pol-specific IFNγ ELISpot Responses by RouteS
FC
/106
PB
MC
* Mann-Whitney Test
Kruskall-Wallis Test: p=0.3853;Dunn's Multiple Comparison (adjusted for multiple comparison):p>0.05 between all groups
* Mann-Whitney Test
Kruskall-Wallis Test: p=0.2565;Dunn's Multiple Comparison (adjusted for multiple comparison):p>0.05 between all groups
rBCG IV
rBCG ID
rBCG IM
Control
0
1000
2000
3000
4000
5000
p=0.0499*
p=0.0242*
p=0.4970*
rBCG IV
rBCG ID
rBCG IM
Control
0
1000
2000
3000
4000
5000
p=0.8334*
p=0.3572*
p=0.1521*
Figure #5d
2 weeks after rAd5 4 weeks after rAd5
10 weeks after rAd5 21 weeks after rAd5
SIV Gag-specific Tetramer Responses by Dosage
% T
etra
mer
bin
din
g
CD
8+ T
cel
ls
10^9
IV
10^8
IV
10^7
IV
10^6
IV
Control
0
2
4
6
8
10
12
10^9
IV
10^8
IV
10^7
IV
10^6
IV
Control
0
2
4
6
8
10
12
10^9
IV
10^8
IV
10^7
IV
10^6
IV
Control
0
2
4
6
8
10
12
10^9
IV
10^8
IV
10^7
IV
10^6
IV
Control
0
2
4
6
8
10
12
Figure #6
SIV Gag-specific p11C Tetramer Responses by Route%
Tet
ram
er b
ind
ing
C
D8+
T c
ells
2 weeks after rAd5
* Mann-Whitney Test
Kruskall-Wallis Test: p=0.0132;Dunn's Multiple Comparison (adjusted for multiple comparison): p<0.05 for IV vs. Control: significantp<0.05 for ID vs. Control: significantp>0.05 for all other group comparisons
Median ± Interquartile Range
* Mann-Whitney Test
Kruskall-Wallis Test: p=0.1733;Dunn's Multiple Comparison (adjusted for multiple comparison): p>0.05 for all groups
4 weeks after rAd5
rBCG IV
rBCG ID
rBCG IM
Control
0
2
4
6
8
10
12
p=0.0121*
p=0.0242*
p=0.1049*
rBCG IV
rBCG ID
rBCG IM
Control
0
2
4
6
8
10
12
p=0.0650*
p=0.2788*
p=0.6824*
Figure #7a
% T
etra
mer
bin
din
g
CD
8+ T
cel
ls
10 weeks after rAd5
Median ± Interquartile Range
21 weeks after rAd5
* Mann-Whitney Test
Kruskall-Wallis Test : p=0.0869;Dunn's Multiple Comparison (adjusted for multiple comparison): p>0.05 for all groups
* Mann-Whitney Test
Kruskall-Wallis Test : p=0.0823;Dunn's Multiple Comparison (adjusted for multiple comparison): p>0.05 for all groups
SIV Gag-specific p11C Tetramer Responses by Route
rBCG IV
rBCG ID
rBCG IM
Control
0
2
4
6
8
10
12
p=0.0650*
p=0.0848*
p=0.9212*
rBCG IV
rBCG ID
rBCG IM
Control
0
2
4
6
8
10
12
p=0.1017*
p=0.0499*
p=0.9185*
Figure #7b
% T
etra
mer
bin
din
g
CD
8+ T
cel
ls
SIV Gag-specific p11C Tetramer Responses
by Route and Dosage
Median
0 10 20 30 40 50 600
2
4
6
8
10
Control106 cfu rBCG IV107 cfu rBCG IV108 cfu rBCG IV109 cfu rBCG IV
Weeks after immunization
0 10 20 30 40 50 600
2
4
6
8
10
Control106 109 cfu rBCG ID
0 10 20 30 40 50 600
2
4
6
8
10109 cfu rBCG IM108 cfu rBCG IM107 cfu rBCG IM106 cfu rBCG IMControl
rBCG rAd5rBCGFigure #8
rAd5
SIV Pol-specific p68 Tetramer Responses
Median
% T
etra
mer
bin
din
g
CD
8+ T
cel
ls
40 45 50 55 60 650.0
0.1
0.2
0.3
0.4rBCG IVrBCG IDrBCG IMControl
Weeks after immunization
Figure #9
+IF
N-
+TN
F- IL-2
+ +IF
N-
+TN
F- IL-2
+
0
1
2
3
4
5
rBCGControl
ICS SIV Gag Peptide Pool Stimulation
3 weeks after rAd5
Median ± Interquartile Range
% C
yto
kin
e+ G
ated
on
CD
8+3+
+IF
N-
+TN
F- IL-2
+ +IF
N-
+TN
F- IL-2
+
0.0
0.1
0.2
0.3
rBCGControl
% C
yto
kin
e+ G
ated
on
CD
4+3+
Figure #10
IFN-IL-2TNF-α
+++
++-
+-+
+--
-++
-+-
--+
CD8+ T cellsB)
CD4 CD80
1
2
3
4
5A)
CD4 CD80
1
2
3
4
5
CD4 CD80
1
2
3
4
5
CD8CD4
Median ± Interquartile Range
% c
yto
kin
e+rBCG IV rBCG ID rAd5
ICS p11C Peptide StimulationFigure #11a
IV ID rAd50
2
4
6
8
10
% C
D8+
T c
ells
IV ID rAd50
25
50
75
100
% p
11C
+C
D8+
T c
ells
IV ID rAd50
20
40
60
80
100
% p
11C
+C
D8+
T c
ells
IV ID rAd50
20
40
60
80
100
% p
11C
+C
D8+
T c
ells
IV ID rAd50
20
40
60
80
100
% p
11C
+C
D8+
T c
ells
IV ID rAd50
25
50
75
% p
11C
+C
D8+
T c
ells
Median ± Interquartile Range
p11C CD28+ Total cytokine
IFN-γ TNF-α IL-2
ICS p11C Peptide Stimulation
Figure #11b
