Cellular and humoral responses to an HIV DNA prime by electroporation boosted with recombinant vesicular stomatitis virus expressing HIV subtype C Env in a randomized controlled clinical trial

• DOI: 10.1016/j.vaccine.2023.03.015
• Publication Date: 2023-03-18T00:10:59Z
• Authors: Gregory J. Wilson; Benigno Rodriguez; Shuying Sue Li; Mary Allen; Ian Frank; Erika Rudnicki; Meg Trahey; Spyros Kalams; Drew Hannaman; David K. Clarke; Rong Xu; Michael Egan; John Eldridge; Michael Pensiero; Theresa Latham; Guido Ferrari; David C. Montefiori; Georgia D. Tomaras; Stephen C. De Rosa; Jeffrey M. Jacobson; Maurine D. Miner; Marnie Elizaga
• Keywords: Adult; AIDS Vaccines; Electroporation; Immunization, Secondary; Vaccines, DNA; Animals; Humans; HIV Infections; DNA; HIV Antibodies; Vesicular Stomatitis; Antibodies, Neutralizing; 3. Good health

HIV subtypes B and C together account for around 60% of HIV-1 cases worldwide. We evaluated the safety and immunogenicity of a subtype B DNA vaccine prime followed by a subtype C viral vector boost.Fourteen healthy adults received DNA plasmid encoding HIV-1 subtype B nef/tat/vif and env (n = 11) or placebo (n = 3) intramuscularly (IM) via electroporation (EP) at 0, 1, and 3 months, followed by IM injection of recombinant vesicular stomatitis virus encoding subtype C Env or placebo at 6 and 9 months. Participants were assessed for safety, tolerability of EP, and Env-specific T-cell and antibody responses.EP was generally well tolerated, although some device-related adverse events did occur, and vaccine reactogenicity was mild to moderate. The vaccine stimulated Env-specific CD4 + T-cell responses in greater than 80% of recipients, and CD8 + T-cell responses in 30%. Subtype C Env-specific IgG binding antibodies (bAb) were elicited in all vaccine recipients, and antibody-dependent cell-mediated cytotoxicity (ADCC) responses to vaccine-matched subtype C targets in 80%. Negligible V1/V2 and neutralizing antibody (nAb) responses were detected.This prime/boost regimen was safe and tolerable, with some device-related events, and immunogenic. Although immunogenicity missed targets for an HIV vaccine, the DNA/rVSV platform may be useful for other applications.gov: NCT02654080.