Vaccination with heterologous HIV envelope sequences and heterologous adenovirus vectors increases T cell responses to conserved regions (HVTN 083).

Publication Type:

Journal Article

Source:

The Journal of infectious diseases (2015)

Abstract:

BACKGROUND:  Increasing the breadth of HIV vaccine-elicited immune responses or targeting conserved regions may improve coverage of circulating strains. HVTN 083 tested whether cellular immune responses with these features are induced by prime-boost strategies employing heterologous vectors, heterologous inserts, or a combination of both.

METHODS:  180 participants were randomized to combinations of adenovirus vectors (Ad5 or Ad35) and HIV-1 envelope (Env) gene inserts (clade A or B) in a prime-boost regimen.

RESULTS:  T cell responses to heterologous and homologous insert regimens targeted a similar number of epitopes (ratio of means=1.0, 95%CI=[0.6, 1.6], p=0.91), however heterologous insert regimens induced significantly more epitopes that were shared between EnvA and EnvB than homologous insert regimens (ratio of means=2.7, 95%CI=[1.2, 5.7], p=0.01). Participants in the heterologous versus homologous insert groups had T cell responses that targeted epitopes with greater evolutionary conservation (entropy 0.32±0.1 bits, p=0.003) and epitopes recognized by responders provided higher coverage (49%, p=0.035). Heterologous vector regimens had higher numbers of total, EnvA, and EnvB epitopes than homologous vector regimens (p=0.02, 0.044, 0.045 respectively).

CONCLUSION:  These data demonstrate that vaccination with heterologous insert prime-boosting increased T cell responses to shared epitopes while heterologous vector prime-boosting increased the number of T cell epitopes recognized.