Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants.
BACKGROUND:The safety and immunogenicity of SAAVI DNA-C2 (4 mg IM), SAAVI MVA-C (2.9 x 109 pfu IM) and Novartis V2-deleted subtype C gp140 (100 mcg) with MF59 adjuvant in various vaccination regimens was evaluated in HIV-uninfected adults in South Africa. METHODS:Participants at three South African...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5008759?pdf=render |
| _version_ | 1818129680334585856 |
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| author | Gavin Churchyard Koleka Mlisana Shelly Karuna Anna-Lise Williamson Carolyn Williamson Lynn Morris Georgia D Tomaras Stephen C De Rosa Peter B Gilbert Niya Gu Chenchen Yu Nonhlanhla N Mkhize Tandile Hermanus Mary Allen Michael Pensiero Susan W Barnett Glenda Gray Linda-Gail Bekker David C Montefiori James Kublin Lawrence Corey |
| author_facet | Gavin Churchyard Koleka Mlisana Shelly Karuna Anna-Lise Williamson Carolyn Williamson Lynn Morris Georgia D Tomaras Stephen C De Rosa Peter B Gilbert Niya Gu Chenchen Yu Nonhlanhla N Mkhize Tandile Hermanus Mary Allen Michael Pensiero Susan W Barnett Glenda Gray Linda-Gail Bekker David C Montefiori James Kublin Lawrence Corey |
| author_sort | Gavin Churchyard |
| collection | DOAJ |
| description | BACKGROUND:The safety and immunogenicity of SAAVI DNA-C2 (4 mg IM), SAAVI MVA-C (2.9 x 109 pfu IM) and Novartis V2-deleted subtype C gp140 (100 mcg) with MF59 adjuvant in various vaccination regimens was evaluated in HIV-uninfected adults in South Africa. METHODS:Participants at three South African sites were randomized (1:1:1:1) to one of four vaccine regimens: MVA prime, sequential gp140 protein boost (M/M/P/P); concurrent MVA/gp140 (MP/MP); DNA prime, sequential MVA boost (D/D/M/M); DNA prime, concurrent MVA/gp140 boost (D/D/MP/MP) or placebo. Peak HIV specific humoral and cellular responses were measured. RESULTS:184 participants were enrolled: 52% were female, all were Black/African, median age was 23 years (range, 18-42 years) and 79% completed all vaccinations. 159 participants reported at least one adverse event, 92.5% were mild or moderate. Five, unrelated, serious adverse events were reported. The M/M/P/P and D/D/MP/MP regimens induced the strongest peak neutralizing and binding antibody responses and the greatest CD4+ T-cell responses to Env. All peak neutralizing and binding antibody responses decayed with time. The MVA, but not DNA, prime contributed to the humoral and cellular immune responses. The D/D/M/M regimen was poorly immunogenic overall but did induce modest CD4+ T-cell responses to Gag and Pol. CD8+ T-cell responses to any antigen were low for all regimens. CONCLUSIONS:The SAAVI DNA-C2, SAAVI MVA-C and Novartis gp140 with MF59 adjuvant in various combinations were safe and induced neutralizing and binding antibodies and cellular immune responses. Sequential immunization with gp140 boosted immune responses primed by MVA or DNA. The best overall immune responses were seen with the M/M/P/P regimen. TRIAL REGISTRATION:ClinicalTrials.gov NCT01418235. |
| first_indexed | 2024-12-11T07:53:00Z |
| format | Article |
| id | doaj.art-6d43c6ed52f448908e78006f87e2d4c2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T07:53:00Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6d43c6ed52f448908e78006f87e2d4c22022-12-22T01:15:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01119e016175310.1371/journal.pone.0161753Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants.Gavin ChurchyardKoleka MlisanaShelly KarunaAnna-Lise WilliamsonCarolyn WilliamsonLynn MorrisGeorgia D TomarasStephen C De RosaPeter B GilbertNiya GuChenchen YuNonhlanhla N MkhizeTandile HermanusMary AllenMichael PensieroSusan W BarnettGlenda GrayLinda-Gail BekkerDavid C MontefioriJames KublinLawrence CoreyBACKGROUND:The safety and immunogenicity of SAAVI DNA-C2 (4 mg IM), SAAVI MVA-C (2.9 x 109 pfu IM) and Novartis V2-deleted subtype C gp140 (100 mcg) with MF59 adjuvant in various vaccination regimens was evaluated in HIV-uninfected adults in South Africa. METHODS:Participants at three South African sites were randomized (1:1:1:1) to one of four vaccine regimens: MVA prime, sequential gp140 protein boost (M/M/P/P); concurrent MVA/gp140 (MP/MP); DNA prime, sequential MVA boost (D/D/M/M); DNA prime, concurrent MVA/gp140 boost (D/D/MP/MP) or placebo. Peak HIV specific humoral and cellular responses were measured. RESULTS:184 participants were enrolled: 52% were female, all were Black/African, median age was 23 years (range, 18-42 years) and 79% completed all vaccinations. 159 participants reported at least one adverse event, 92.5% were mild or moderate. Five, unrelated, serious adverse events were reported. The M/M/P/P and D/D/MP/MP regimens induced the strongest peak neutralizing and binding antibody responses and the greatest CD4+ T-cell responses to Env. All peak neutralizing and binding antibody responses decayed with time. The MVA, but not DNA, prime contributed to the humoral and cellular immune responses. The D/D/M/M regimen was poorly immunogenic overall but did induce modest CD4+ T-cell responses to Gag and Pol. CD8+ T-cell responses to any antigen were low for all regimens. CONCLUSIONS:The SAAVI DNA-C2, SAAVI MVA-C and Novartis gp140 with MF59 adjuvant in various combinations were safe and induced neutralizing and binding antibodies and cellular immune responses. Sequential immunization with gp140 boosted immune responses primed by MVA or DNA. The best overall immune responses were seen with the M/M/P/P regimen. TRIAL REGISTRATION:ClinicalTrials.gov NCT01418235.http://europepmc.org/articles/PMC5008759?pdf=render |
| spellingShingle | Gavin Churchyard Koleka Mlisana Shelly Karuna Anna-Lise Williamson Carolyn Williamson Lynn Morris Georgia D Tomaras Stephen C De Rosa Peter B Gilbert Niya Gu Chenchen Yu Nonhlanhla N Mkhize Tandile Hermanus Mary Allen Michael Pensiero Susan W Barnett Glenda Gray Linda-Gail Bekker David C Montefiori James Kublin Lawrence Corey Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants. PLoS ONE |
| title | Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants. |
| title_full | Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants. |
| title_fullStr | Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants. |
| title_full_unstemmed | Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants. |
| title_short | Sequential Immunization with gp140 Boosts Immune Responses Primed by Modified Vaccinia Ankara or DNA in HIV-Uninfected South African Participants. |
| title_sort | sequential immunization with gp140 boosts immune responses primed by modified vaccinia ankara or dna in hiv uninfected south african participants |
| url | http://europepmc.org/articles/PMC5008759?pdf=render |
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