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.
<h4>Background</h4>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 Af...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-03-01
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| Series: | PLoS Medicine |
| Online Access: | https://doi.org/10.1371/journal.pmed.1004360 |
| _version_ | 1797217046096773120 |
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| author | Zoe Moodie Erica Andersen-Nissen Nicole Grunenberg One B Dintwe Faatima Laher Omar Jia J Kee Linda-Gail Bekker Fatima Laher Nivashnee Naicker Ilesh Jani Nyaradzo M Mgodi Portia Hunidzarira Modulakgota Sebe Maurine D Miner Laura Polakowski Shelly Ramirez Michelle Nebergall Simbarashe Takuva Lerato Sikhosana Jack Heptinstall Kelly E Seaton Stephen De Rosa Carlos A Diazgranados Marguerite Koutsoukos Olivier Van Der Meeren Susan W Barnett Niranjan Kanesa-Thasan James G Kublin Georgia D Tomaras M Juliana McElrath Lawrence Corey Kathryn Mngadi Paul Goepfert HVTN 107 Protocol Team |
| author_facet | Zoe Moodie Erica Andersen-Nissen Nicole Grunenberg One B Dintwe Faatima Laher Omar Jia J Kee Linda-Gail Bekker Fatima Laher Nivashnee Naicker Ilesh Jani Nyaradzo M Mgodi Portia Hunidzarira Modulakgota Sebe Maurine D Miner Laura Polakowski Shelly Ramirez Michelle Nebergall Simbarashe Takuva Lerato Sikhosana Jack Heptinstall Kelly E Seaton Stephen De Rosa Carlos A Diazgranados Marguerite Koutsoukos Olivier Van Der Meeren Susan W Barnett Niranjan Kanesa-Thasan James G Kublin Georgia D Tomaras M Juliana McElrath Lawrence Corey Kathryn Mngadi Paul Goepfert HVTN 107 Protocol Team |
| author_sort | Zoe Moodie |
| collection | DOAJ |
| description | <h4>Background</h4>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).<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.<h4>Trial registration</h4>HVTN 107 was registered with the South African National Clinical Trials Registry (DOH-27-0715-4894) and ClinicalTrials.gov (NCT03284710). |
| first_indexed | 2024-04-24T11:55:37Z |
| format | Article |
| id | doaj.art-909a7c021d8247d2955cca75b0f8a084 |
| institution | Directory Open Access Journal |
| issn | 1549-1277 1549-1676 |
| language | English |
| last_indexed | 2024-04-24T11:55:37Z |
| publishDate | 2024-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Medicine |
| spelling | doaj.art-909a7c021d8247d2955cca75b0f8a0842024-04-09T05:31:18ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762024-03-01213e100436010.1371/journal.pmed.1004360Safety 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 MoodieErica Andersen-NissenNicole GrunenbergOne B DintweFaatima Laher OmarJia J KeeLinda-Gail BekkerFatima LaherNivashnee NaickerIlesh JaniNyaradzo M MgodiPortia HunidzariraModulakgota SebeMaurine D MinerLaura PolakowskiShelly RamirezMichelle NebergallSimbarashe TakuvaLerato SikhosanaJack HeptinstallKelly E SeatonStephen De RosaCarlos A DiazgranadosMarguerite KoutsoukosOlivier Van Der MeerenSusan W BarnettNiranjan Kanesa-ThasanJames G KublinGeorgia D TomarasM Juliana McElrathLawrence CoreyKathryn MngadiPaul GoepfertHVTN 107 Protocol Team<h4>Background</h4>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).<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.<h4>Trial registration</h4>HVTN 107 was registered with the South African National Clinical Trials Registry (DOH-27-0715-4894) and ClinicalTrials.gov (NCT03284710).https://doi.org/10.1371/journal.pmed.1004360 |
| spellingShingle | Zoe Moodie Erica Andersen-Nissen Nicole Grunenberg One B Dintwe Faatima Laher Omar Jia J Kee Linda-Gail Bekker Fatima Laher Nivashnee Naicker Ilesh Jani Nyaradzo M Mgodi Portia Hunidzarira Modulakgota Sebe Maurine D Miner Laura Polakowski Shelly Ramirez Michelle Nebergall Simbarashe Takuva Lerato Sikhosana Jack Heptinstall Kelly E Seaton Stephen De Rosa Carlos A Diazgranados Marguerite Koutsoukos Olivier Van Der Meeren Susan W Barnett Niranjan Kanesa-Thasan James G Kublin Georgia D Tomaras M Juliana McElrath Lawrence Corey Kathryn Mngadi Paul Goepfert 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 Medicine |
| title | 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. |
| title_full | 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. |
| title_fullStr | 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. |
| title_full_unstemmed | 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. |
| title_short | 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. |
| title_sort | 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 |
| url | https://doi.org/10.1371/journal.pmed.1004360 |
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