HIV-DNA Priming Alters T Cell Responses to HIV-Adenovirus Vaccine Even When Responses to DNA Are Undetectable

Abstract

Many candidate HIV vaccines are designed to primarily elicit T-cell responses. Although repeated immunization with the same vaccine boosts antibody responses, the benefit for T-cell responses is ill-defined. We compared two immunization regimens that include the same recombinant adenoviral serotype 5 (rAd5) boost. Repeated homologous rAd5 immunization fails to increase T-cell responses, but increases gp140 antibody responses ten-fold. DNA prime, as compared with rAd5 prime, directs long-term memory CD8+ T cells toward a terminally differentiated effector memory phenotype with cytotoxic potential. Based on the kinetics of activated cells measured directly ex vivo, the DNA vaccination primes for both CD4+ and CD8+ T cells, despite the lack of detection of the latter until after the boost. These results suggest that heterologous prime-boost combinations have distinct immunological advantages over homologous prime-boosts, and suggest that the effect of DNA on subsequent boosting may not be easily detectable directly after the DNA vaccination.

CXCL13 is a plasma biomarker of germinal center activity

“…Yellow fever vaccine recipients received the Food and Drug Administration-approved 17D yellow fever vaccine (37). Plasma samples from HIV-uninfected candidate vaccine recipients from the HVTN068 trial (38) were analyzed for CXCL13 in plasma after a booster immunization (Ad5/HIV) given at the 6-mo time point. Primary immunizations were either Ad5/HIV at month 0 or DNA/HIV at months 0 and 1.…”

“…The first cohort was a vaccine cohort immunized with the Food and Drug Administration-approved yellow fever virus vaccine (37). The second group comprised study participants in an HIV Vaccine Trials Network (HVTN) protocol testing a candidate HIV vaccine regimen (HVTN068) (38).…”

Importância da resposta aos epítopos subdominantes, da proliferação e da recirculação de linfócitos T CD8+ durante a vacinação experimental contra a infecção pelo Trypanosoma cruzi.

“…In parallel, recombinant AdHu5 boosting of DNA-primed individuals resulted in significantly higher immune responses (De Rosa et al, 2011). The anti-vector immunity can be either antibody mediated or independent (Cockburn et al, 2008;Schirmbeck et al, 2008;Frahm et al, 2012).…”

“…This strategy has proved successful in some relevant experimental models such as simian immunodeficiency virus (SIV), malaria, Marburg, and Ebola virus infection, and Chagas disease (American trypanosomiasis), providing a considerable degree of protective immunity Santra et al, 2005;Acierno et al, 2006;Mattapallil et al, 2006;Sun et al, 2006;Martins et al, 2010;. These relative successes obtained in pre-clinical experimental models fueled human phase I trials Churchyard et al, 2011;De Rosa et al, 2011).…”

“…The most frequent example of this across different models is specific CD8 + T cells producing IFN-γ and TNF simultaneously. High frequencies of polyfunctional specific CD8 + T cells were described in (i) mice (Masopust et al, 2006;Duke et al, 2007;Elvang et al, 2009;Reyes-Sandoval et al, 2010;Rodríguez et al, 2012;Vijayan et al, 2012), (ii) NHP (Mattapallil et al, 2006;Sun et al, 2006;Cox et al, 2008;Liu et al, 2008;Magalhaes et al, 2008;Cayabyab et al, 2009;Wilks et al, 2010;Hutnick et al, 2012), and (iii) humans (Beveridge et al, 2007;Harari et al, 2008;Winstone et al, 2009;Churchyard et al, 2011;De Rosa et al, 2011).…”