Background: Despite increased availability of new options for HIV prevention, the epidemic remains insufficiently controlled, highlighting the need for a prophylactic vaccine. In APPROACH we evaluated seven combinations of viral vectors expressing mosaic HIV-1 Env/Gag/Pol antigens and high-dose (HD) or low-dose (LD) aluminum phosphate adjuvanted clade C Env gp140 protein. All regimens were well tolerated and immunogenic. Two regimens were selected for longer-term follow-up.
Methods: In this unblinded follow-up of APPROACH (phase 1/2a randomized, double-blind, placebo-controlled study) long-term safety and immunogenicity were evaluated at Wk120 and Wk144 in healthy uninfected adults who had received Ad26.Mos.HIV (week [Wk]0 and Wk12) and Ad26.Mos.HIV, gp140HD or LD (Wk24 and Wk48).
Results: 65 participants (18-49 years) vaccinated with Ad26.Mos.HIV, gp140HD (32) or LD (33) entered the long-term follow-up (from Thailand, Rwanda, Uganda, South Africa and USA).
No serious adverse events were reported during follow-up. Immune responses were maintained in both groups with 100% responders to autologous Clade C ELISA at Wk120 and Wk144, in the HD group. Geometric mean titres were 3.5 and 3.3 Log10 at Wk120, and 3.4 and 3.2 Log10 at Wk144, in the HD and LD groups, respectively. Maintained responses were observed over the second year post last vaccination, remaining in the same range as those measured at Wk78 and Wk96. Comparison to a parallel NHP challenge study showed that Wk120 and Wk144 ELISA titers remained higher than NHP responses at Wk72 when they were protected against SHIV challenge.
Conclusions: In this 2-year post-vaccination follow-up of APPROACH, we observed durable humoral immune responses over 2 years with 100% response rate in the participants receiving the Ad26.Mos.HIV, gp140HD vaccine regimen. No safety issues were seen. Additional immunological analyses and follow-up will continue (approximately 6 year post-vaccination).

Env ELISA IgG-t gp140: Clade C (C97ZA.012)
[Env ELISA IgG-t gp140: Clade C (C97ZA.012)]