Transcriptomic profiling of rhesus macaques vaccinated with Ad26/ALVAC+gp120 or DNA/ALVAC+gp120

We contrasted innate and adaptive immune responses of HIV vaccine candidates of varying efficacy in macaques that shared the ALVAC+gp120 protein boost with an ALVAC, DNA or Ad26 prime modality. The vaccine efficacies of the DNA/ALVAC+gp120 and ALVAC/ALVAC+gp120 vaccine regimens, both protective, were associated with qualitative temporal-spatial differences in the innate CD14+ and CD16+ cells in blood and tissues. The activation of hypoxia and the inflammasome in CD14+ DR+ CD16- classical monocytes and CD4+ Th2 responses correlated with a decreased risk of SIVmac251 acquisition. CD4+ Th2 cells, in turn, correlated with mucosal NKp44+ cells and mucosal protective antibodies to V2. In contrast, the Ad26/ALVAC+gp120 vaccine resulted in increased de novo differentiated CX3CR1+ CD163+ macrophages in lymph nodes, increased CD4+ Th17 cells in blood and rectal mucosa, and a lack vaccine efficacy. These data posit that the engagement of classical monocytes and inflammasome activation is central for the elicitation of protective innate and adaptive responses by the ALVAC-based HIV vaccine platform. Twenty four (24) rhesus macaques were randomized to two vaccination groups. One group (n=12) was primed once with Ad26 (at week 0) and boosted twice with ALVAC-SIV/gp120 in Alum adjuvant (at week 12 and week 24). The second group (n=12) was primed twice with DNA (at week 0 and week 4) and boosted twice with ALVAC-SIV/gp120 in Alum adjuvant (at week 12 and week 24). Blood samples were taken pre-vaccination, 24 hours after the first boost (week 12), 2 weeks after the first boost (week 14), 24 hours after the second boost (week 24) and 1 week after the second boost (week 15). All the samples were taken before SIV challenge. One animal (R270) who received the Ad26/ALVAC+gp120 vaccine was not included in the transcriptomic study because of a lack of blood samples. Blood samples were conserved in PAXgene tubes. RNA was extracted and hybridized to Illumina beadchips.