Transcriptional profiling of macaques treated with ALVAC- and NYVAC-SIV+gp120 alum vaccines

We compare the immunogenicity of ALVAC- or NYVAC- based SIVmac251 vaccine regimens combined with gp120/alum boosts and their relative efficacy in a cohort of 65 female rhesus macaques. Both NYVAC- and ALVAC-based regimens induced equivalent titers of serum binding antibodies to gp120, whereas NYVAC elicited significantly higher envelope specific T cell responses. Surprisingly, however, only the ALVAC-based regimen was able to significantly decrease the risk of SIVmac251 acquisition following repeated low-dose intravaginal challenges. The risk of virus acquisition was associated negatively with the frequency of classical monocytes and positively with non-classical. The systems biology approach used to investigate the molecular basis of the different vaccine efficacies demonstrated specific expression profiles elicited by the ALVAC-based regimen that correlate with efficacy. A total of 65 female rhesus macaques were randomized into five groups: ALVAC-SIV/gp120 (20 animals), NYVAC-SIV/gp120 (20 animals), ALVAC-control (10 animals), NYVAC-control (10 animals), and naïve (5 animals). The animals in the ALVAC-SIV/gp120 and NYVAC-SIV/gp120 groups were immunized at weeks 0, 4, 12, and 24 with ALVAC-SIV (vCP180) or NYVAC-SIV (VP1071) carrying the identical Env-Gag-Pol genes, respectively. At weeks 12 and 24, the animals from these groups received an alum-formulated gp120 protein boost. The animals in the ALVAC-control and NYVAC-control groups were immunized at weeks 0, 4, 12, and 24 with empty ALVAC-SIV (vCP180) or NYVAC-SIV (VP1071) vectors, respectively. At weeks 12 and 24, the animals from these groups received alum. technical replicate: P168_A06015_w0.6h, P168_A06015_w0.6h_rep1 technical replicate: P168_A06028_w0.6h_rep1, P168_A06028_w0.6h_rep2 technical replicate: P168_A06082_w0.0h, P168_A06082_w0.0h_rep1 technical replicate: P168_A06083_w0.24h, P168_A06083_w0.24h_rep1