Background: Mosaic HIV-1 antigens induce broad immune responses and aim to provide protection against diverse HIV-1 strains. Heterologous vaccination regimens including Ad26 and gp140 have conferred significant protection in NHP, and were safe and immunogenic in humans.
To optimize breadth, and refine the vaccine composition, ASCENT assessed adding Mosaic1 gp140 to clade C gp140 in the regimen.
Methods: This study was conducted in adults in Kenya, Rwanda and the USA. Participants were randomized to Ad26.Mos4.HIV at weeks 0 and 12, and Ad26.Mos4.HIV and alum adjuvanted gp140 Env protein (250µg clade C gp140 or bivalent clade C-Mosaic1 gp140, each 125µg) at weeks 24 and 48 or placebo.
Serious adverse events (AEs) were assessed throughout the study, unsolicited AEs until 28 days post-each vaccination, and solicited AEs until 7 days post-each vaccination.
Results: 152 healthy adults (18-50 years; 59% females) were vaccinated with Ad26.Mos4.HIV and clade C gp140 (n=26), Ad26.Mos4.HIV and bivalent gp140 (n=100) or placebo (n=26). Active regimens were well tolerated (most AEs were mild/moderate; no serious AEs).
HIV Env-specific binding antibody levels and subclass distribution showed both regimens induced binding and functional antibodies to all antigens tested (Figure). Clade C responses were not attenuated by replacing half the clade C dose with Mosaic1 gp140, while clade B responses improved (p< 0.05).
At week 28, similar PTE Env ELISpot responses were observed, with medians of 444 and 452 SFU/106 PBMC in bivalent or clade C groups, respectively. CD4+ (but not CD8+) T-cell ICS responses increased to Mos1 gp120 peptides in the bivalent relative to clade C group (0.147% vs 0.123% IL-2 and/or IFNγ+ CD4 T-cells, 81% vs 50% response, respectively).
Conclusions: Both regimens were well tolerated and immunogenic. ASCENT supports using bivalent clade C-Mosaic1 gp140 with Ad26.Mos4.HIV for expanded clade coverage in the phase 3 efficacy study trial starting in 2019.

Geometric mean ratio (95% CI) of tetravalent clade c-Mos/tetravalent clade C groups for Week 52
[Geometric mean ratio (95% CI) of tetravalent clade c-Mos/tetravalent clade C groups for Week 52 ]