Sequential Immunization with gp140 boosts immune responses primed by modified vaccinia Ankara or DNA in HIV-uninfected South African participants

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dc.contributor.authorChurchyard, Gavinen_ZA
dc.contributor.authorMlisana, Kolekaen_ZA
dc.contributor.authorKaruna, Shellyen_ZA
dc.contributor.authorWilliamson, Anna-Liseen_ZA
dc.contributor.authorWilliamson, Carolynen_ZA
dc.contributor.authorMorris, Lynnen_ZA
dc.contributor.authorTomaras, Georgia Den_ZA
dc.contributor.authorDe Rosa, Stephen Cen_ZA
dc.contributor.authorGilbert, Peter Ben_ZA
dc.contributor.authorGu, Niyaen_ZA
dc.contributor.authorYu, Chenchenen_ZA
dc.contributor.authorMkhize, Nonhlanhla Nen_ZA
dc.contributor.authorHermanus, Tandileen_ZA
dc.contributor.authorAllen, Maryen_ZA
dc.contributor.authorPensiero, Michaelen_ZA
dc.contributor.authorBarnett, Susan Wen_ZA
dc.contributor.authorGray, Glendaen_ZA
dc.contributor.authorBekker, Linda-Gailen_ZA
dc.contributor.authorMontefiori, David Cen_ZA
dc.contributor.authorKublin, Jamesen_ZA
dc.contributor.authorCorey, Lawrenceen_ZA
dc.date.accessioned2016-10-31T07:34:43Z
dc.date.available2016-10-31T07:34:43Z
dc.date.issued2016en_ZA
dc.description.abstractBACKGROUND: The safety and immunogenicity of SAAVI DNA-C2 (4 mg IM), SAAVI MVA-C (2.9 x 10 9 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 NCT01418235en_ZA
dc.identifier.apacitationChurchyard, G., Mlisana, K., Karuna, S., Williamson, A., Williamson, C., Morris, L., ... Corey, L. (2016). Sequential Immunization with gp140 boosts immune responses primed by modified vaccinia Ankara or DNA in HIV-uninfected South African participants. <i>PLoS One</i>, http://hdl.handle.net/11427/22340en_ZA
dc.identifier.chicagocitationChurchyard, Gavin, Koleka Mlisana, Shelly Karuna, Anna-Lise Williamson, Carolyn Williamson, Lynn Morris, Georgia D Tomaras, et al "Sequential Immunization with gp140 boosts immune responses primed by modified vaccinia Ankara or DNA in HIV-uninfected South African participants." <i>PLoS One</i> (2016) http://hdl.handle.net/11427/22340en_ZA
dc.identifier.citationChurchyard, G., Mlisana, K., Karuna, S., Williamson, A. L., Williamson, C., Morris, L., ... & Yu, C. (2016). Sequential Immunization with gp140 boosts immune responses primed by modified vaccinia Ankara or DNA in HIV-uninfected South African participants. PloS one, 11(9), e0161753. doi:10.1371/journal.pone.0161753en_ZA
dc.identifier.ris TY - Journal Article AU - Churchyard, Gavin AU - Mlisana, Koleka AU - Karuna, Shelly AU - Williamson, Anna-Lise AU - Williamson, Carolyn AU - Morris, Lynn AU - Tomaras, Georgia D AU - De Rosa, Stephen C AU - Gilbert, Peter B AU - Gu, Niya AU - Yu, Chenchen AU - Mkhize, Nonhlanhla N AU - Hermanus, Tandile AU - Allen, Mary AU - Pensiero, Michael AU - Barnett, Susan W AU - Gray, Glenda AU - Bekker, Linda-Gail AU - Montefiori, David C AU - Kublin, James AU - Corey, Lawrence AB - BACKGROUND: The safety and immunogenicity of SAAVI DNA-C2 (4 mg IM), SAAVI MVA-C (2.9 x 10 9 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 DA - 2016 DB - OpenUCT DO - 10.1371/journal.pone.0161753 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2016 T1 - Sequential Immunization with gp140 boosts immune responses primed by modified vaccinia Ankara or DNA in HIV-uninfected South African participants TI - Sequential Immunization with gp140 boosts immune responses primed by modified vaccinia Ankara or DNA in HIV-uninfected South African participants UR - http://hdl.handle.net/11427/22340 ER - en_ZA
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0161753en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/22340
dc.identifier.vancouvercitationChurchyard G, Mlisana K, Karuna S, Williamson A, Williamson C, Morris L, et al. Sequential Immunization with gp140 boosts immune responses primed by modified vaccinia Ankara or DNA in HIV-uninfected South African participants. PLoS One. 2016; http://hdl.handle.net/11427/22340.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Virologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherAntibody responseen_ZA
dc.subject.otherAntibodiesen_ZA
dc.subject.otherVaccinesen_ZA
dc.subject.otherImmune responseen_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherVaccination and immunizationen_ZA
dc.subject.otherAntigensen_ZA
dc.subject.otherDNA-binding proteinsen_ZA
dc.titleSequential Immunization with gp140 boosts immune responses primed by modified vaccinia Ankara or DNA in HIV-uninfected South African participantsen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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