The following is a summary of “Safety and Immunogenicity of Ad26-Vectored HIV Vaccine With Mosaic Immunogens and a Novel Mosaic Envelope Protein in HIV-Uninfected Adults: A Phase 1/2a Study,” published in the April 2023 issue of Infectious Diseases by Stieh, et al.

For a placebo-controlled, double-blind, phase 1/2a study was to evaluate the safety and antibody response of a new adenovirus 26-based HIV-1 vaccine encoding 2 mosaic Gag and Pol, and 2 mosaic Env proteins plus adjuvanted clade C gp140 (referred to as clade C regimen) and to compare it to a bivalent protein regimen (clade C regimen plus mosaic gp140) and placebo in healthy, HIV-uninfected adults at low risk for HIV infection.

Healthy adults at low risk of HIV infection were enrolled in this placebo-controlled, double-blind, phase 1/2a research. They were randomly assigned (1:4:1) to receive 4 doses of an adenovirus 26-based HIV-1 vaccine expressing 2 mosaic Gag, Pol, and Env proteins plus adjuvanted clade C gp140 (referred to here as clade C regimen), a bivalent protein regimen (clade C regimen plus mosaic gp140), or a placebo. Safety and antibody responses were the main endpoints.

About 152/155 participants received at least one injection (clade C, n = 26; bivalent protein, n = 103; placebo, n = 26). The highest severity of the adverse event (AE) was grade 3 (local pain/tenderness, 12%, 2%, and 0% of the respective groups; solicited systemic AEs, 19%, 15%, 0%). After dose 4, HIV-1 mosaic gp140-binding antibody titers were 79,595 ELISA units (EU)/mL and 137,520 EU/mL in the clade C and bivalent protein groups (P < .001), respectively. Six months later, antibody titers were 16,862 EU/mL and 25,162 EU/mL in the clade C and bivalent protein groups. The bivalent protein group had the highest antibody response breadth against clade C gp140 and clade C/non-clade C gp120. Adding mosaic gp140 to the clade C regimen increased and broadened the elicited immune response without compromising safety or clade C responses.

The study showed that adding mosaic gp140 to the clade C regimen increased and broadened the elicited immune response without compromising safety or clade C responses. The bivalent protein regimen showed the highest antibody response breadth against clade C gp140 and clade C/non-clade C gp120. Developing a globally effective HIV vaccine is crucial for eliminating HIV, and the study provided important insights for future HIV vaccine development.

Source: academic.oup.com/jid/article-abstract/227/8/939/6812747?redirectedFrom=fulltext