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Safety and immunogenicity of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120 vaccine boost adjuvanted with MF59 or alum in healthy adults without HIV (HVTN 107): A phase 1/2a randomized trial.

Publication ,  Journal Article
Moodie, Z; Andersen-Nissen, E; Grunenberg, N; Dintwe, OB; Omar, FL; Kee, JJ; Bekker, L-G; Laher, F; Naicker, N; Jani, I; Mgodi, NM; Sebe, M ...
Published in: PLoS Med
March 2024

BACKGROUND: 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). METHODS AND FINDINGS: 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. All vaccinations were safe and well-tolerated; increased alanine aminotransferase was the most frequent related adverse event, occurring in 2 (1.5%) participants (1 severe, 1 mild). At month 6.5, vaccine-specific gp120 IgG binding antibodies were detected in 100% of vaccinees for all 4 vaccine groups. No significant differences were seen in the occurrence and net MFI of vaccine-specific IgA responses between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/alum-prime-boost groups or between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/MF59 coadministration groups. Limitations were the relatively small sample size per group and lack of evaluation of higher gp120 doses. CONCLUSIONS: 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. TRIAL REGISTRATION: HVTN 107 was registered with the South African National Clinical Trials Registry (DOH-27-0715-4894) and ClinicalTrials.gov (NCT03284710).

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Published In

PLoS Med

DOI

EISSN

1549-1676

Publication Date

March 2024

Volume

21

Issue

3

Start / End Page

e1004360

Location

United States

Related Subject Headings

  • Vaccines, Synthetic
  • Vaccines, Combined
  • Squalene
  • Polysorbates
  • Immunoglobulin G
  • Immunoglobulin A
  • Immunogenicity, Vaccine
  • Humans
  • HIV-1
  • HIV Infections
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Moodie, Z., Andersen-Nissen, E., Grunenberg, N., Dintwe, O. B., Omar, F. L., Kee, J. J., … HVTN 107 Protocol Team. (2024). Safety and immunogenicity of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120 vaccine boost adjuvanted with MF59 or alum in healthy adults without HIV (HVTN 107): A phase 1/2a randomized trial. PLoS Med, 21(3), e1004360. https://doi.org/10.1371/journal.pmed.1004360
Moodie, Zoe, Erica Andersen-Nissen, Nicole Grunenberg, One B. Dintwe, Faatima Laher Omar, Jia J. Kee, Linda-Gail Bekker, et al. “Safety and immunogenicity of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120 vaccine boost adjuvanted with MF59 or alum in healthy adults without HIV (HVTN 107): A phase 1/2a randomized trial.PLoS Med 21, no. 3 (March 2024): e1004360. https://doi.org/10.1371/journal.pmed.1004360.
Moodie Z, Andersen-Nissen E, Grunenberg N, Dintwe OB, Omar FL, Kee JJ, Bekker L-G, Laher F, Naicker N, Jani I, Mgodi NM, Hunidzarira P, Sebe M, Miner MD, Polakowski L, Ramirez S, Nebergall M, Takuva S, Sikhosana L, Heptinstall J, Seaton KE, De Rosa S, Diazgranados CA, Koutsoukos M, Van Der Meeren O, Barnett SW, Kanesa-Thasan N, Kublin JG, Tomaras GD, McElrath MJ, Corey L, Mngadi K, Goepfert P, HVTN 107 Protocol Team. Safety and immunogenicity of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120 vaccine boost adjuvanted with MF59 or alum in healthy adults without HIV (HVTN 107): A phase 1/2a randomized trial. PLoS Med. 2024 Mar;21(3):e1004360.

Published In

PLoS Med

DOI

EISSN

1549-1676

Publication Date

March 2024

Volume

21

Issue

3

Start / End Page

e1004360

Location

United States

Related Subject Headings

  • Vaccines, Synthetic
  • Vaccines, Combined
  • Squalene
  • Polysorbates
  • Immunoglobulin G
  • Immunoglobulin A
  • Immunogenicity, Vaccine
  • Humans
  • HIV-1
  • HIV Infections