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Clinical Trial
. 2009 Aug;15(8):873-5.
doi: 10.1038/nm.1991. Epub 2009 Jul 20.

Adenovirus-specific immunity after immunization with an Ad5 HIV-1 vaccine candidate in humans

Kara L O'Brien  1 , Jinyan Liu, Sharon L King, Ying-Hua Sun, Joern E Schmitz, Michelle A Lifton, Natalie A Hutnick, Michael R Betts, Sheri A Dubey, Jaap Goudsmit, John W Shiver, Michael N Robertson, Danilo R Casimiro, Dan H Barouch
Affiliations
Clinical Trial

Adenovirus-specific immunity after immunization with an Ad5 HIV-1 vaccine candidate in humans

Kara L O'Brien et al. Nat Med. 2009 Aug.

Abstract

The immunologic basis for the potential enhanced HIV-1 acquisition in adenovirus serotype 5 (Ad5)-seropositive individuals who received the Merck recombinant Ad5 HIV-1 vaccine in the STEP study remains unclear. Here we show that baseline Ad5-specific neutralizing antibodies are not correlated with Ad5-specific T lymphocyte responses and that Ad5-seropositive subjects do not develop higher vector-specific cellular immune responses as compared with Ad5-seronegative subjects after vaccination. These findings challenge the hypothesis that activated Ad5-specific T lymphocytes were the cause of the potential enhanced HIV-1 susceptibility in the STEP study.

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Figures

Figure 1
Figure 1
Ad-specific humoral and cellular immune responses before and after rAd5-Gag vaccination. (a) Correlation between Ad5-specific IFN-γ ELISPOT responses and Ad5-specific NAb titers at baseline. (b) Ad5-specific NAb titers and (c) Ad5-specific IFN-γ ELISPOT responses as stratified by vaccine dose (1010 vp, 1011 vp), baseline Ad5 titer (<18, >18), and study timepoint (week 0, week 8). (d) Ad26-, (e) Ad35-, and (f) Ad48-specific IFN-γ ELISPOT responses.
Figure 1
Figure 1
Ad-specific humoral and cellular immune responses before and after rAd5-Gag vaccination. (a) Correlation between Ad5-specific IFN-γ ELISPOT responses and Ad5-specific NAb titers at baseline. (b) Ad5-specific NAb titers and (c) Ad5-specific IFN-γ ELISPOT responses as stratified by vaccine dose (1010 vp, 1011 vp), baseline Ad5 titer (<18, >18), and study timepoint (week 0, week 8). (d) Ad26-, (e) Ad35-, and (f) Ad48-specific IFN-γ ELISPOT responses.
Figure 2
Figure 2
Magnitude and phenotype of Ad-specific and total CD4+ T lymphocyte subpopulations before and after 1011 vp rAd5-Gag vaccination. (a) Ad5- (top panels) and Ad26- (bottom panels) specific IFN-γ+CD4+ (left panels) and IFN-γ+CD8+ (right panels) ICS responses as stratified by baseline Ad5 titer (<18, >18) and study timepoint (week 0, week 8). (b) Total, CCR5+, CD45RO+CD27+ central memory (CM), and CD45RO+CD27− effector memory (EM) CD4+ T lymphocyte subpopulations. (c) Ki67+ activation of total, CM, EM, and CD45RO−CD27− effector (E) CD4+ T lymphocyte subpopulations. (d) Ki67+ activation of total, CM, EM, and E CCR5+CD4+ T lymphocyte subpopulations.
Figure 2
Figure 2
Magnitude and phenotype of Ad-specific and total CD4+ T lymphocyte subpopulations before and after 1011 vp rAd5-Gag vaccination. (a) Ad5- (top panels) and Ad26- (bottom panels) specific IFN-γ+CD4+ (left panels) and IFN-γ+CD8+ (right panels) ICS responses as stratified by baseline Ad5 titer (<18, >18) and study timepoint (week 0, week 8). (b) Total, CCR5+, CD45RO+CD27+ central memory (CM), and CD45RO+CD27− effector memory (EM) CD4+ T lymphocyte subpopulations. (c) Ki67+ activation of total, CM, EM, and CD45RO−CD27− effector (E) CD4+ T lymphocyte subpopulations. (d) Ki67+ activation of total, CM, EM, and E CCR5+CD4+ T lymphocyte subpopulations.
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