Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef vaccine Induced immune responses

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dc.contributor.authorHopkins, Kathryn Len_ZA
dc.contributor.authorLaher, Fatimaen_ZA
dc.contributor.authorOtwombe, Kennedyen_ZA
dc.contributor.authorChurchyard, Gavinen_ZA
dc.contributor.authorBekker, Linda-Gailen_ZA
dc.contributor.authorDeRosa, Stephenen_ZA
dc.contributor.authorNchabeleng, Maphoshaneen_ZA
dc.contributor.authorMlisana, Kolekaen_ZA
dc.contributor.authorKublin, Jamesen_ZA
dc.contributor.authorGray, Glendaen_ZA
dc.date.accessioned2015-12-20T16:03:54Z
dc.date.available2015-12-20T16:03:54Z
dc.date.issued2014en_ZA
dc.description.abstractBACKGROUND: Phambili, the Merck (MRK)-Adenovirus Type 5 (Ad5) HIV-1 gag/pol/nef subtype B vaccine study, conducted in South Africa, suspended enrollment and vaccination when companion study, Step, was found non-efficacious. Although the vaccine did not prevent HIV-1 infection or lower viral-load setpoint, immune responses recognized clades B and C HIV-1 subtypes. We investigated predictors of the vaccine-induced antigen-specific immune responses. METHODS: Vaccine-induced immunogenicity was ascertained by interferon-γ ELISpot assays on the first 186 enrolled participants receiving two vaccinations. Analyses, stratified by study arm/sex, were performed on baseline demographics [sex, age, Body Mass Index (BMI), site, Adenovirus Type-5 (Ad5) titer, Herpes Simplex Virus Type-2 (HSV2) status, heavy drinking]. Multivariate logistic regression determined predictors. RESULTS: Of the 186 participants, 53.7% (n = 100) were female, median BMI was 22.5 [IQR: 20.4-27.0], 85.5% (n = 159) were Ad5 seropositive, and 18.8% (n = 35) drank heavily. All vaccine recipients responded to both clade B (n = 87; 47%) and/or C (n = 74; 40%), p = 0.17. In multivariate analysis, female sex [Adjusted Odds Ratio (AOR): 6.478; p = 0.0159], overweight/obese BMI (AOR: 0.186; p = 0.0452), and heavy drinking (AOR: 0.270; p = 0.048) significantly predicted immune response to clade C for any antigens. A marginally significant predictor of clade C-pol antigen was female sex (AOR: 3.182; p = 0.0500). CONCLUSIONS: Sex, BMI, and heavy drinking affected vaccine-induced HIV-1 specific immune responses to clade C antigens. The role of female sex and overweight/obese BMI boosting and suppressing vaccine-induced HIV-1 specific immune responses, respectively, requires elucidation, including any effect on HIV vaccine efficacy, especially in the era of colliding epidemics (HIV and obesity).en_ZA
dc.identifier.apacitationHopkins, K. L., Laher, F., Otwombe, K., Churchyard, G., Bekker, L., DeRosa, S., ... Gray, G. (2014). Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef vaccine Induced immune responses. <i>PLoS One</i>, http://hdl.handle.net/11427/15911en_ZA
dc.identifier.chicagocitationHopkins, Kathryn L, Fatima Laher, Kennedy Otwombe, Gavin Churchyard, Linda-Gail Bekker, Stephen DeRosa, Maphoshane Nchabeleng, Koleka Mlisana, James Kublin, and Glenda Gray "Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef vaccine Induced immune responses." <i>PLoS One</i> (2014) http://hdl.handle.net/11427/15911en_ZA
dc.identifier.citationHopkins, K. L., Laher, F., Otwombe, K., Churchyard, G., Bekker, L. G., DeRosa, S., ... & Gray, G. (2013). Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef Vaccine Induced Immune Responses. PloS one, 9(8), e103446. doi:10.1371/journal.pone.0103446en_ZA
dc.identifier.ris TY - Journal Article AU - Hopkins, Kathryn L AU - Laher, Fatima AU - Otwombe, Kennedy AU - Churchyard, Gavin AU - Bekker, Linda-Gail AU - DeRosa, Stephen AU - Nchabeleng, Maphoshane AU - Mlisana, Koleka AU - Kublin, James AU - Gray, Glenda AB - BACKGROUND: Phambili, the Merck (MRK)-Adenovirus Type 5 (Ad5) HIV-1 gag/pol/nef subtype B vaccine study, conducted in South Africa, suspended enrollment and vaccination when companion study, Step, was found non-efficacious. Although the vaccine did not prevent HIV-1 infection or lower viral-load setpoint, immune responses recognized clades B and C HIV-1 subtypes. We investigated predictors of the vaccine-induced antigen-specific immune responses. METHODS: Vaccine-induced immunogenicity was ascertained by interferon-γ ELISpot assays on the first 186 enrolled participants receiving two vaccinations. Analyses, stratified by study arm/sex, were performed on baseline demographics [sex, age, Body Mass Index (BMI), site, Adenovirus Type-5 (Ad5) titer, Herpes Simplex Virus Type-2 (HSV2) status, heavy drinking]. Multivariate logistic regression determined predictors. RESULTS: Of the 186 participants, 53.7% (n = 100) were female, median BMI was 22.5 [IQR: 20.4-27.0], 85.5% (n = 159) were Ad5 seropositive, and 18.8% (n = 35) drank heavily. All vaccine recipients responded to both clade B (n = 87; 47%) and/or C (n = 74; 40%), p = 0.17. In multivariate analysis, female sex [Adjusted Odds Ratio (AOR): 6.478; p = 0.0159], overweight/obese BMI (AOR: 0.186; p = 0.0452), and heavy drinking (AOR: 0.270; p = 0.048) significantly predicted immune response to clade C for any antigens. A marginally significant predictor of clade C-pol antigen was female sex (AOR: 3.182; p = 0.0500). CONCLUSIONS: Sex, BMI, and heavy drinking affected vaccine-induced HIV-1 specific immune responses to clade C antigens. The role of female sex and overweight/obese BMI boosting and suppressing vaccine-induced HIV-1 specific immune responses, respectively, requires elucidation, including any effect on HIV vaccine efficacy, especially in the era of colliding epidemics (HIV and obesity). DA - 2014 DB - OpenUCT DO - 10.1371/journal.pone.0103446 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef vaccine Induced immune responses TI - Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef vaccine Induced immune responses UR - http://hdl.handle.net/11427/15911 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/15911
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0103446
dc.identifier.vancouvercitationHopkins KL, Laher F, Otwombe K, Churchyard G, Bekker L, DeRosa S, et al. Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef vaccine Induced immune responses. PLoS One. 2014; http://hdl.handle.net/11427/15911.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDesmond Tutu HIV Centreen_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.holder© 2014 Hopkins et alen_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.otherImmune responseen_ZA
dc.subject.otherVaccinesen_ZA
dc.subject.otherEnzyme-linked immunoassaysen_ZA
dc.subject.otherHIV-1en_ZA
dc.subject.otherHIV vaccinesen_ZA
dc.subject.otherBody mass indexen_ZA
dc.subject.otherObesityen_ZA
dc.subject.otherAntigensen_ZA
dc.titlePredictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef vaccine Induced immune responsesen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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