Safety and immunogenicity of a subtype C ALVAC-HIV

• Published in: PLoS medicine Vol. 21; no. 3
• Main Authors: Moodie, Zoe, Andersen-Nissen, Erica, Grunenberg, Nicole, Dintwe, One B, Omar, Faatima Laher, Kee, Jia J, Bekker, Linda-Gail, Laher, Fatima, Naicker, Nivashnee, Jani, Ilesh, Mgodi, Nyaradzo M, Hunidzarira, Portia, Sebe, Modulakgota, Miner, Maurine D, Polakowski, Laura, Ramirez, Shelly, Nebergall, Michelle, Takuva, Simbarashe, Sikhosana, Lerato, Heptinstall, Jack, Seaton, Kelly E, De Rosa, Stephen, Diazgranados, Carlos A, Koutsoukos, Marguerite, Van Der Meeren, Olivier, Barnett, Susan W, Kanesa-thasan, Niranjan, Kublin, James G, Tomaras, Georgia D, McElrath, M. Juliana, Corey, Lawrence, Mngadi, Kathryn, Goepfert, Paul
• Format: Journal Article
• Language: English
• Published: Public Library of Science 19-03-2024
• Subjects: Adults; AIDS vaccines; Clinical trials; Comparative analysis; HIV (Viruses); HIV infection; Immune response; Immunoglobulin A; Immunoglobulin G; Immunological adjuvants; Prevention; Product development; Testing; Vaccination; Zimbabwe; South Africa; Mozambique; Thailand
• ISSN: 1549-1277
• DOI: 10.1371/journal.pmed.1004360

Adjuvants are widely used to enhance and/or direct vaccine-induced immune responses yet rarely evaluated head-to-head. Our trial directly compared immune responses elicited by MF59 versus alum adjuvants in the RV144-like HIV vaccine regimen modified for the Southern African region. The RV144 trial of a recombinant canarypox vaccine vector expressing HIV env subtype B (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost adjuvanted with alum is the only trial to have shown modest HIV vaccine efficacy. Data generated after RV144 suggested that use of MF59 adjuvant might allow lower protein doses to be used while maintaining robust immune responses. We evaluated safety and immunogenicity of an HIV recombinant canarypox vaccine vector expressing HIV env subtype C (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost (gp120) adjuvanted with alum (ALVAC-HIV+gp120/alum) or MF59 (ALVAC-HIV+gp120/MF59) or unadjuvanted (ALVAC-HIV+gp120/no-adjuvant) and a regimen where ALVAC-HIV+gp120 adjuvanted with MF59 was used for the prime and boost (ALVAC-HIV+gp120/MF59 coadministration). Between June 19, 2017 and June 14, 2018, 132 healthy adults without HIV in South Africa, Zimbabwe, and Mozambique were randomized to receive intramuscularly: (1) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/MF59 (months 3, 6, and 12), n = 36; (2) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/alum (months 3, 6, and 12), n = 36; (3) 4 doses of ALVAC-HIV+gp120/MF59 coadministered (months 0, 1, 6, and 12), n = 36; or (4) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/no adjuvant (months 3, 6, and 12), n = 24. Primary outcomes were safety and occurrence and mean fluorescence intensity (MFI) of vaccine-induced gp120-specific IgG and IgA binding antibodies at month 6.5. Although MF59 was expected to enhance immune responses, alum induced similar responses to MF59, suggesting that the choice between these adjuvants may not be critical for the ALVAC+gp120 regimen.