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

 

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dc.contributor.author Hopkins, Kathryn L en_ZA
dc.contributor.author Laher, Fatima en_ZA
dc.contributor.author Otwombe, Kennedy en_ZA
dc.contributor.author Churchyard, Gavin en_ZA
dc.contributor.author Bekker, Linda-Gail en_ZA
dc.contributor.author DeRosa, Stephen en_ZA
dc.contributor.author Nchabeleng, Maphoshane en_ZA
dc.contributor.author Mlisana, Koleka en_ZA
dc.contributor.author Kublin, James en_ZA
dc.contributor.author Gray, Glenda en_ZA
dc.date.accessioned 2015-12-20T16:03:54Z
dc.date.available 2015-12-20T16:03:54Z
dc.date.issued 2014 en_ZA
dc.identifier.citation Hopkins, 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.0103446 en_ZA
dc.identifier.uri http://hdl.handle.net/11427/15911
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0103446
dc.description.abstract 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). en_ZA
dc.language.iso eng en_ZA
dc.publisher Public Library of Science en_ZA
dc.rights This 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.uri http://creativecommons.org/licenses/by/4.0 en_ZA
dc.source PLoS One en_ZA
dc.source.uri http://journals.plos.org/plosone en_ZA
dc.subject.other Immune response en_ZA
dc.subject.other Vaccines en_ZA
dc.subject.other Enzyme-linked immunoassays en_ZA
dc.subject.other HIV-1 en_ZA
dc.subject.other HIV vaccines en_ZA
dc.subject.other Body mass index en_ZA
dc.subject.other Obesity en_ZA
dc.subject.other Antigens en_ZA
dc.title Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef vaccine Induced immune responses en_ZA
dc.type Journal Article en_ZA
dc.rights.holder © 2014 Hopkins et al en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Desmond Tutu HIV Centre en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Hopkins, 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/11427/15911 en_ZA
dc.identifier.chicagocitation Hopkins, 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/11427/15911 en_ZA
dc.identifier.vancouvercitation Hopkins 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.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


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This 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. Except where otherwise noted, this item's license is described as This 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.