A systems biology approach revealed distinct host responses between ALVAC-SIV and NYVAC-SIV vaccines during an evaluation of immunogenicity in rheusus macaques

Though only modestly effective, RV144 is the first HIV vaccine clinical trial to show efficacy against heterosexual transmission. It tested ALVAC-HIV (a canarypox vector expressing HIV Gag, Pro and gp120) in the prime-boost combination with AIDSVAX B/E (a HIV bivalent gp120). To understand the immune correlates and inform future trials, we repeated this regimen in a rhesus model and contrasted two different pox vectors. Our study consisted of 24 animals in four groups: two initially receiving ALVAC-SIV or the vaccinia vector NYVAC-SIV (both expressing SIV Gag, Pol and Env) as the prime, with later addition of SIV gp120 and alum boosts; and two control groups receiving empty ALVAC or NYVAC and alum only. Microarray analysis of whole blood samples showed that as early as 6 hours after the initial immunization, the gene expression features of the ALVAC-SIV group were distinct from the animals receiving NYVAC-SIV, with innate immunity pathways activated in an ALVAC-SIV-specific manner. By 24 hours post vaccination, ALVAC-SIV induced more differentially expressed (DE) genes than the other three groups relative to the pre-immunization baseline, and NYVAC-SIV and NYVAC control induced similar numbers of DE genes. We will relate these very early host responses to the differences in immunogenicity observed over the course of immunization. The impact of these early events on the later outcomes will be determined once the protective efficacies of the two vaccines are determined.