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Title: Landscapes of binding antibody and T-cell responses to pox-protein HIV vaccines in Thais and South Africans
Authors: Lue Ping Zhao
Andrew Fiore-Gartland
Lindsay N. Carpp
Kristen W. Cohen
Nadine Rouphael
Llewellyn Fleurs
One Dintwe
Michael Zhao
Zoe Moodie
Youyi Fong
Nigel Garrett
Ying Huang
Craig Innes
Holly E. Janes
Erica Lazarus
Nelson L. Michael
Sorachai Nitayaphan
Punnee Pitisuttithum
Supachai Rerks-Ngarm
Merlin L. Robb
Stephen C. de Rosa
Lawrence Corey
Glenda E. Gray
Kelly E. Seaton
Nicole L. Yates
M. Juliana McElrath
Nicole Frahm
Georgia D. Tomaras
Peter B. Gilbert
Centre for the AIDS Programme of Research in South Africa
South African Medical Research Council
University of Witwatersrand
Armed Forces Research Institute of Medical Sciences, Thailand
Thailand Ministry of Public Health
University of Washington, Seattle
Walter Reed Army Institute of Research
Mahidol University
Duke University
Duke University School of Medicine
Fred Hutchinson Cancer Research Center
Emory University
University of Cape Town
Bill & Melinda Gates Medical Research Institute
Klerksdorp Research Centre
Hutchinson Centre Research Institute of South Africa
Keywords: Agricultural and Biological Sciences;Biochemistry, Genetics and Molecular Biology;Multidisciplinary
Issue Date: 1-Jan-2020
Citation: PLoS ONE. Vol.15, No.1 (2020)
Abstract: © 2020 Wei et al. 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. HIV vaccine trials routinely measure multiple vaccine-elicited immune responses to compare regimens and study their potential associations with protection. Here we employ unsupervised learning tools facilitated by a bidirectional power transformation to explore the multivariate binding antibody and T-cell response patterns of immune responses elicited by two pox-protein HIV vaccine regimens. Both regimens utilized a recombinant canarypox vector (ALVAC-HIV) prime and a bivalent recombinant HIV-1 Envelope glycoprotein 120 subunit boost. We hypothesized that within each trial, there were participant subgroups sharing similar immune responses and that their frequencies differed across trials.Methods and findings We analyzed data from three trials–RV144 (NCT00223080), HVTN 097 (NCT02109354), and HVTN 100 (NCT02404311), the latter of which was pivotal in advancing the tested poxprotein HIV vaccine regimen to the HVTN 702 Phase 2b/3 efficacy trial. We found that bivariate CD4+ T-cell and anti-V1V2 IgG/IgG3 antibody response patterns were similar by age, sex-at-birth, and body mass index, but differed for the pox-protein clade AE/B alum-adjuvanted regimen studied in RV144 and HVTN 097 (PAE/B/alum) compared to the pox-protein clade C/C MF59-adjuvanted regimen studied in HVTN 100 (PC/MF59). Specifically, more PAE/B/alum recipients had low CD4+ T-cell and high anti-V1V2 IgG/IgG3 responses, and more PC/MF59 recipients had broad responses of both types. Analyses limited to “vaccinematched” antigens suggested that some of the differences in responses between the regimens could have been due to antigens in the assays that did not match the vaccine immunogens. Our approach was also useful in identifying subgroups with unusually absent or high co-responses across assay types, flagging individuals for further characterization by functional assays. We also found that co-responses of anti-V1V2 IgG/IgG3 and CD4+ T cells had broad variability. As additional immune response assays are standardized and validated, we anticipate our framework will be increasingly valuable for multivariate analysis.Conclusions Our approach can be used to advance vaccine development objectives, including the characterization and comparison of candidate vaccine multivariate immune responses and improved design of studies to identify correlates of protection. For instance, results suggested that HVTN 702 will have adequate power to interrogate immune correlates involving anti-V1V2 IgG/IgG3 and CD4+ T-cell co-readouts, but will have lower power to study antigp120/ gp140 IgG/IgG3 due to their lower dynamic ranges. The findings also generate hypotheses for future testing in experimental and computational analyses aimed at achieving a mechanistic understanding of vaccine-elicited immune response heterogeneity.
ISSN: 19326203
Appears in Collections:Scopus 2020

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