Publication:
Neutralization Takes Precedence Over IgG or IgA Isotype-related Functions in Mucosal HIV-1 Antibody-mediated Protection

Issued Date

2016-12-01

Resource Type

Article

ISSN

23523964

DOI

10.1016/j.ebiom.2016.11.024

Other identifier(s)

2-s2.0-85003794530

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

EBioMedicine. Vol.14, (2016), 97-111

Suggested Citation

Rena D. Astronomo, Sampa Santra, Lamar Ballweber-Fleming, Katharine G. Westerberg, Linh Mach, Tiffany Hensley-McBain, Laura Sutherland, Benjamin Mildenberg, Georgeanna Morton, Nicole L. Yates, Gregory J. Mize, Justin Pollara, Florian Hladik, Christina Ochsenbauer, Thomas N. Denny, Ranjit Warrier, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Jaranit Kaewkungwal, Guido Ferrari, George M. Shaw, Shi Mao Xia, Hua Xin Liao, David C. Montefiori, Georgia D. Tomaras, Barton F. Haynes, M. Juliana McElrath Neutralization Takes Precedence Over IgG or IgA Isotype-related Functions in Mucosal HIV-1 Antibody-mediated Protection. EBioMedicine. Vol.14, (2016), 97-111. doi:10.1016/j.ebiom.2016.11.024 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/42826

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Title

Neutralization Takes Precedence Over IgG or IgA Isotype-related Functions in Mucosal HIV-1 Antibody-mediated Protection

Author(s)

Rena D. Astronomo
 Sampa Santra
 Lamar Ballweber-Fleming
 Katharine G. Westerberg
 Linh Mach
 Tiffany Hensley-McBain
 Laura Sutherland
 Benjamin Mildenberg
 Georgeanna Morton
 Nicole L. Yates
 Gregory J. Mize
 Justin Pollara
 Florian Hladik
 Christina Ochsenbauer
 Thomas N. Denny
 Ranjit Warrier
 Supachai Rerks-Ngarm
 Punnee Pitisuttithum
 Sorachai Nitayapan
 Jaranit Kaewkungwal
 Guido Ferrari
 George M. Shaw
 Shi Mao Xia
 Hua Xin Liao
 David C. Montefiori
 Georgia D. Tomaras
 Barton F. Haynes
 M. Juliana McElrath

Other Contributor(s)

Fred Hutchinson Cancer Research Center
 Beth Israel Deaconess Medical Center
 Duke University
 University of Washington, Seattle
 University of Alabama at Birmingham
 University of Pennsylvania
 Thailand Ministry of Public Health
 Mahidol University
 Armed Forces Research Institute of Medical Sciences, Thailand

Abstract

© 2016 The Authors HIV-1 infection occurs primarily through mucosal transmission. Application of biologically relevant mucosal models can advance understanding of the functional properties of antibodies that mediate HIV protection, thereby guiding antibody-based vaccine development. Here, we employed a human ex vivo vaginal HIV-1 infection model and a rhesus macaque in vivo intrarectal SHIV challenge model to probe the protective capacity of monoclonal broadly-neutralizing (bnAb) and non-neutralizing Abs (nnAbs) that were functionally modified by isotype switching. For human vaginal explants, we developed a replication-competent, secreted NanoLuc reporter virus system and showed that CD4 binding site bnAbs b12 IgG1 and CH31 IgG1 and IgA2 isoforms potently blocked HIV-1JR-CSFand HIV-1Bal26infection. However, IgG1 and IgA nnAbs, either alone or together, did not inhibit infection despite the presence of FcR-expressing effector cells in the tissue. In macaques, the CH31 IgG1 and IgA2 isoforms infused before high-dose SHIV challenge were completely to partially protective, respectively, while nnAbs (CH54 IgG1 and CH38 mIgA2) were non-protective. Importantly, in both mucosal models IgG1 isotype bnAbs were more protective than the IgA2 isotypes, attributable in part to greater neutralization activity of the IgG1 variants. These findings underscore the importance of potent bnAb induction as a primary goal of HIV-1 vaccine development.

Keyword(s)

Biochemistry, Genetics and Molecular Biology

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/42826

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Scopus 2016-2017