APPROACH Long-Term Results Promising for Ad26.Mos.HIV, gp140HD Vaccine Regimen

Although options for HIV prevention, such as pre-exposure prophylaxis, are becoming increasingly more available, new cases of HIV continue to emerge across the world. In hopes of eliminating new cases of HIV entirely, investigators are working towards developing a prophylactic HIV vaccine.

The APPROACH trial, a phase 1/2a randomized, double-blind, placebo-controlled study, evaluated 7 combinations of viral vectors that expressed mosaic HIV-1 Env/Gag/Pol antigens and a high-dose (HD) or low-dose (LD) aluminum phosphate adjuvanted clade C Env gp140 protein.

The study found that all regimens were both well-tolerated and immunogenic, but 2 regimens in particular were selected for long-term follow up.

The results of the unblinded follow-up were presented in an oral abstract session at the 10^th IAS Conference on HIV Science (IAS 2019).

The APPROACH follow-up evaluated safety and immunogenicity data at week 120 and 144 in healthy, uninfected adults who had received Ad26.Mos.HIV (at week 0 and week 12) and Ad26.Mos.HIV, gp140 HD or LD (week 24 and week 48).

The study followed 65 participants from Thailand, Rwanda, Uganda, South Africa, and the United States between the ages of 18-49 years who had been vaccinated with Ad26.Mos.HIV. In total, 32 were vaccinated with gp140 HD and 33 received LD.

According to the abstract, there were no serious adverse events reported during the follow-up period and immune responses were maintained in both groups with 100% responders to autologous Clade C ELISA at week 120 and week 144 in the HD group.

The investigators reported that geometric mean titers were 3.5 and 3.3 Log₁₀ at week 120, and 3.4 and 3.2 Log₁₀ at week 144, 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 week 78 and week 96,” the investigators wrote.

The study further notes that comparisons to a non-human primate study indicated that week 120 and 140 ELISA titers remained higher than the responses at week 72, at which they were protected against Simian immunodeficiency virus, an animal virus comparable to HIV in humans.

“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,” the investigators concluded.

The study team reported that additional immunological analyses and follow-up will continue for approximately 6 years post-vaccination.

The study, “Two-year post-vaccination follow-up from APPROACH: Phase 1/2a randomized study evaluating safety and immunogenicity of prophylactic HIV vaccine regimens combining Ad26.Mos.HIV and gp140 envelope protein,” was presented on Tuesday, July 23, 2019, at IAS 2019 in Mexico City, Mexico.