Assessment of the safety and immunogenicity of 2 novel vaccine platforms for HIV-1 prevention: a randomized trial
Annals of internal medicine, 2016•acpjournals.org
Background: A prophylactic HIV-1 vaccine is a global health priority. Objective: To assess a
novel vaccine platform as a prophylactic HIV-1 regimen. Design: Randomized, double-blind,
placebo-controlled trial. Both participants and study personnel were blinded to treatment
allocation.(ClinicalTrials. gov: NCT01215149) Setting: United States, East Africa, and South
Africa. Patients: Healthy adults without HIV infection. Intervention: 2 HIV-1 vaccines
(adenovirus serotype 26 with an HIV-1 envelope A insert [Ad26. EnvA] and adenovirus …
novel vaccine platform as a prophylactic HIV-1 regimen. Design: Randomized, double-blind,
placebo-controlled trial. Both participants and study personnel were blinded to treatment
allocation.(ClinicalTrials. gov: NCT01215149) Setting: United States, East Africa, and South
Africa. Patients: Healthy adults without HIV infection. Intervention: 2 HIV-1 vaccines
(adenovirus serotype 26 with an HIV-1 envelope A insert [Ad26. EnvA] and adenovirus …
Background
A prophylactic HIV-1 vaccine is a global health priority.
Objective
To assess a novel vaccine platform as a prophylactic HIV-1 regimen.
Design
Randomized, double-blind, placebo-controlled trial. Both participants and study personnel were blinded to treatment allocation. (ClinicalTrials.gov: NCT01215149)
Setting
United States, East Africa, and South Africa.
Patients
Healthy adults without HIV infection.
Intervention
2 HIV-1 vaccines (adenovirus serotype 26 with an HIV-1 envelope A insert [Ad26.EnvA] and adenovirus serotype 35 with an HIV-1 envelope A insert [Ad35.Env], both administered at a dose of 5 × 1010 viral particles) in homologous and heterologous combinations.
Measurements
Safety and immunogenicity and the effect of baseline vector immunity.
Results
217 participants received at least 1 vaccination, and 210 (>96%) completed follow-up. No vaccine-associated serious adverse events occurred. All regimens were generally well-tolerated. All regimens elicited humoral and cellular immune responses in nearly all participants. Preexisting Ad26- or Ad35-neutralizing antibody titers had no effect on vaccine safety and little effect on immunogenicity. In both homologous and heterologous regimens, the second vaccination significantly increased EnvA antibody titers (approximately 20-fold from the median enzyme-linked immunosorbent assay titers of 30–300 to 3000). The heterologous regimen of Ad26–Ad35 elicited significantly higher EnvA antibody titers than Ad35–Ad26. T-cell responses were modest and lower in East Africa than in South Africa and the United States.
Limitations
Because the 2 envelope inserts were not identical, the boosting responses were complex to interpret. Durability of the immune responses elicited beyond 1 year is unknown.
Conclusion
Both vaccines elicited significant immune responses in all populations. Baseline vector immunity did not significantly affect responses. Second vaccinations in all regimens significantly boosted EnvA antibody titers, although vaccine order in the heterologous regimen had a modest effect on the immune response.
Primary Funding Source
International AIDS Vaccine Initiative, National Institutes of Health, Ragon Institute, Crucell Holland.
acpjournals.org