RV 591 RAPIDVAX

To date, several efficacy trials of candidate HIV vaccines have been completed, including VAX003 (Pitisuttithum, 2006), VAX004 (Flynn, 2005), RV144 (Rerks-Ngarm, 2009), STEP (Buchbinder, 2008), HVTN503 (Gray, 2011), HVTN505 (Hammer, 2013), and HVTN702 (Gray, 2021). Multiple early phase trials are active in Africa, though only a few are HIV vaccine efficacy trials, including HVTN503, HVTN702, and HVTN705/HPX2008. Of all listed trials, only RV144, a Phase III HIV vaccine prime/boost trial conducted in Thailand from 2003-2009, showed modest efficacy, with HIV Env antibody being the sole correlate for reduced risk of HIV acquisition (Haynes, 2012). Healthy participants in RV144 who received the 6-month vaccination regimen containing ALVAC-HIV and AIDSVAX® B/E, formulated in aluminum hydroxide, were 31% less likely than placebo recipients to become HIV infected over 3.5 years of follow-up. In post-hoc analysis, efficacy was 60% at 12 months, indicating that protective immunity waned rapidly (Robb, 2012). A subsequent trial, HVTN702, failed to show protection despite using a similar vaccine schedule and immunogens (Gray, 2021), but a different adjuvant. An acute HIV study, RV217, showed that viral replication peaks about 13 days after HIV acquisition with a median of 6.7 log10 HIV RNA copies/mL, suggesting the immune system is unable to produce antibodies at a rate that provides protection, even with bolus vaccine injections.Despite some progress, an effective HIV vaccine does not yet exist, nor has an optimal vaccination schedule been identified to maximize the magnitude and quality of the induced immune response.Objectives:Primary objective is to assess the safety, reactogenicity and tolerability of two vaccination regimens: rapid dose-escalation of CH505 TF chTrimer+ALFQ and Ad26.Mos4.HIV or co-administration of CH505 TF chTrimer+ALFQ and Ad26.Mos4.HIV. Secondary objective is to evaluate HIV-specific antibody responses induced by the two vaccination regimens