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Clinical Trial
. 2024 Mar 19;21(3):e1004360.
doi: 10.1371/journal.pmed.1004360. eCollection 2024 Mar.

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

Zoe Moodie  1 , Erica Andersen-Nissen  1   2 , Nicole Grunenberg  1 , One B Dintwe  1   2 , Faatima Laher Omar  2 , Jia J Kee  1 , Linda-Gail Bekker  3 , Fatima Laher  4 , Nivashnee Naicker  5 , Ilesh Jani  6 , Nyaradzo M Mgodi  7 , Portia Hunidzarira  7 , Modulakgota Sebe  8 , Maurine D Miner  1 , Laura Polakowski  9 , Shelly Ramirez  1 , Michelle Nebergall  1 , Simbarashe Takuva  1 , Lerato Sikhosana  10 , Jack Heptinstall  11 , Kelly E Seaton  11 , Stephen De Rosa  1 , Carlos A Diazgranados  12 , Marguerite Koutsoukos  13 , Olivier Van Der Meeren  14 , Susan W Barnett  15 , Niranjan Kanesa-Thasan  16 , James G Kublin  1 , Georgia D Tomaras  11 , M Juliana McElrath  1 , Lawrence Corey  1 , Kathryn Mngadi  8 , Paul Goepfert  17 ; HVTN 107 Protocol Team
Affiliations
Clinical Trial

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

Zoe Moodie et al. PLoS Med. .

Abstract

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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Conflict of interest statement

MK and OVDM are employed by GSK and hold shares in the company. MK reports grants from Bill & Melinda Gates Foundation and grants from NIH during the conduct of the study. NKT was an employee of GSK Biologicals and Novartis Vaccines & Diagnostics during the time of the trial. All other authors have nothing to declare.

Figures

Fig 1
Fig 1. CONSORT flow diagram: allocation and follow-up for HVTN 107.
HVTN, HIV Vaccine Trials Network; ppt, participant; SPA, study product administration.
Fig 2
Fig 2. Response rates and boxplots of binding antibody IgG responses to the 3 vaccine-matched gp120 antigens at months 6.5, 12, 12.5, and 18.
Significant p-values are shown for comparisons of response rates by Barnard’s exact test and magnitudes among positive responders by Wilcoxon test for the following groups: MF59 vs. none, alum vs. none, MF59 vs. alum, MF59 vs. MF59 co-admin. The fourth and fifth vaccinations are shown by syringe. MFI, mean fluorescence intensity.
Fig 3
Fig 3. Response rates and boxplots of binding antibody IgA responses to the 3 vaccine-matched gp120 antigens at months 6.5 and 12.
The fourth and fifth vaccinations are shown by syringe. MFI, mean fluorescence intensity.
Fig 4
Fig 4. Response rates and boxplots of binding antibody IgG responses to the 3 vaccine-matched V1V2 antigens at months 6.5, 12, 12.5, and 18.
Significant p-values are shown for comparisons of response rates by Barnard’s exact test and magnitudes among positive responders by Wilcoxon test for the following groups: MF59 vs. none, alum vs. none, MF59 vs. alum, MF59 vs. MF59 co-admin. The fourth and fifth vaccinations are shown by syringe. MFI, mean fluorescence intensity.
Fig 5
Fig 5. Response rates and boxplots of CD4+ T-cell responses (measured by expression of IFN-γ and/or IL-2 and/or CD40L) to vaccine-matched antigens at months 6.5, 12, 12.5, and 18.
Significant p-values are shown for comparisons of response rates by Barnard’s exact test and magnitudes among positive responders by Wilcoxon test for the following groups: MF59 vs. none, alum vs. none, MF59 vs. alum, MF59 vs. MF59 co-admin. The fourth and fifth vaccinations are shown by syringe.
See this image and copyright information in PMC

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