Citation Information

Jacobson, J.M., Felber, B.K., Chen, H., Pavlakis, G.N., Mullins, J.I., de Rosa, S.C., Kuritzkes, D.R., Tomaras, G.D., Kinslow, J., Bao, Y., Olefsky, M., Rosati, M., Bear, J., Hannaman, D., Laird, G.M., Cyktor, J.C., Heath, S.L., Collier, A.C., Koletar, S.L., Taiwo, B.O., Tebas, P., Wohl, D.A., Belanzauran-Zamudio, P.F., McElrath, M.J., Landay, A.L., ACGT 5369 Study Team, (2023)The immunogenicity of an HIV-1 Gag conserved element DNA vaccine in people with HIV and receiving antiretroviral therapy. AIDS 2024 Jun 1;38(7):963-973(pubmed) (doi)

Abstract

Objective: The primary objective of the study was to assess the immunogenicity of an HIV-1 Gag conserved element DNA vaccine (p24CE DNA) in people with HIV (PWH) receiving suppressive antiretroviral therapy (ART).

Design: AIDS Clinical Trials Group A5369 was a phase I/IIa, randomized, double-blind, placebo-controlled study of PWH receiving ART with plasma HIV-1 RNA less than 50 copies/ml, current CD4 + T-cell counts greater than 500 cells/ul, and nadir CD4 + T-cell counts greater than 350 cells/ul.

Methods: The study enrolled 45 participants randomized 2 : 1 : 1 to receive p24CE DNA vaccine at weeks 0 and 4, followed by p24CE DNA admixed with full-length p55 Gag DNA vaccine at weeks 12 and 24 (arm A); full-length p55 Gag DNA vaccine at weeks 0, 4, 12, and 24 (arm B); or placebo at weeks 0, 4, 12, and 24 (arm C). The active and placebo vaccines were administered by intramuscular electroporation.

Results: There was a modest, but significantly greater increase in the number of conserved elements recognized by CD4 + and/or CD8 + T cells in arm A compared with arm C ( P = 0.014). The percentage of participants with an increased number of conserved elements recognized by T cells was also highest in arm A (8/18, 44.4%) vs. arm C (0/10, 0.0%) ( P = 0.025). There were no significant differences between treatment groups in the change in magnitude of responses to total conserved elements.

Conclusion: A DNA-delivered HIV-1 Gag conserved element vaccine boosted by a combination of this vaccine with a full-length p55 Gag DNA vaccine induced a new conserved element-directed cellular immune response in approximately half the treated PWH on ART.