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Background: Globally, 1.8 million new HIV infections in 2016 demonstrate the need for a prophylactic HIV vaccine, but none currently exist. APPROACH (NCT02315703) investigates various vaccine regimens (comprising viral vectors with global mosaic HIV-1 Env, Gag and Pol transgenes and a soluble clade C gp140 trimeric envelope protein), that aim to elicit protective immunity against multiple clades of HIV-1. Week 28 and 52 data showed Ad26.Mos.HIV double prime, and Ad26.Mos.HIV or MVA-Mosaic boost regimens combined with gp140 Env protein were immunogenic and well tolerated. We here present data on durability of immune responses.
Methods: Healthy, uninfected participants were randomized into seven vaccine regimens, or a placebo and administered Ad26.Mos.HIV double prime (Weeks 0 and 12) and a double boost of either Ad26.Mos.HIV or MVA-Mosaic, with high- or low-dose aluminium-phosphate adjuvanted gp140 Env protein (Weeks 24 and 48). Vaccine responders were participants exhibiting an immunological response >LLOQ (if baseline is < LLOQ/missing) or 3-fold increase from baseline (if ≥LLOQ). Week 78 and 96 endpoints were immunogenicity and safety/tolerability.
Results: 393 participants from the US, East-Africa, South Africa and Thailand were randomised and received ≥1 dose of study vaccine (n=48-50/group; see figure for regimens). Median age 29 years; 54% male; 54% Black, 27% White and 16% Asian.
Participants in all vaccine regimens showed humoral response rates >92% at Week 78 (30 weeks after fourth dose). Rates of antibody decay after the fourth vaccination exhibited regimen-independent decrease in magnitude. Groups boosted with Ad26.Mos.HIV+gp140 Env (high- or low-dose) maintained 100% response rate (high-dose [n=44]; 95% CI=91.96%-100%; low-dose [n=39]; 95% CI=90.97%-100%).
Bridging with a parallel non-human primate (NHP) challenge study showed for Ad26.Mos.HIV+gp140 Env high-dose boost group, autologous ELISA responses at Week 78 were 4.3-fold higher in humans than in partially protected NHPs at time of challenge.
During the post-fourth vaccination period, safety appeared to remain favorable for all groups.
Conclusions: All participants in Ad26.Mos.HIV prime with Ad26.Mos.HIV+gp140 Env (high- and low-dose protein) groups achieved high and persistent immune responses that were maintained until Week 78 (30 weeks after fourth dose). Follow-up of participants that received Ad26+gp140 Env boosted regimens will continue (5-year).


ELISA ? Total IgG gp140 Env Clade C
[ELISA ? Total IgG gp140 Env Clade C]