Publication:
Landscapes of binding antibody and T-cell responses to pox-protein HIV vaccines in Thais and South Africans

Issued Date

2020-01-01

Resource Type

Article

ISSN

19326203

DOI

10.1371/journal.pone.0226803

Other identifier(s)

2-s2.0-85078710978

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

PLoS ONE. Vol.15, No.1 (2020)

Suggested Citation

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 Landscapes of binding antibody and T-cell responses to pox-protein HIV vaccines in Thais and South Africans. PLoS ONE. Vol.15, No.1 (2020). doi:10.1371/journal.pone.0226803 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/53545

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Title

Landscapes of binding antibody and T-cell responses to pox-protein HIV vaccines in Thais and South Africans

Author(s)

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

Other Contributor(s)

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
 HJF
 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

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.

Keyword(s)

Agricultural and Biological Sciences
 Biochemistry, Genetics and Molecular Biology
 Multidisciplinary

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/53545

Collections

Scopus 2020