Skip to main content
Journal cover image

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

Publication ,  Journal Article
Astronomo, RD; Santra, S; Ballweber-Fleming, L; Westerberg, KG; Mach, L; Hensley-McBain, T; Sutherland, L; Mildenberg, B; Morton, G; Yates, NL ...
Published in: EBioMedicine
December 2016

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-CSF and HIV-1Bal26 infection. 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.

Duke Scholars

Published In

EBioMedicine

DOI

EISSN

2352-3964

Publication Date

December 2016

Volume

14

Start / End Page

97 / 111

Location

Netherlands

Related Subject Headings

  • Vagina
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • Neutralization Tests
  • Mucous Membrane
  • Macaca mulatta
  • Leukocytes
  • Immunophenotyping
  • Immunoglobulin G
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Astronomo, R. D., Santra, S., Ballweber-Fleming, L., Westerberg, K. G., Mach, L., Hensley-McBain, T., … McElrath, J. M. (2016). Neutralization Takes Precedence Over IgG or IgA Isotype-related Functions in Mucosal HIV-1 Antibody-mediated Protection. EBioMedicine, 14, 97–111. https://doi.org/10.1016/j.ebiom.2016.11.024
Astronomo, Rena D., Sampa Santra, Lamar Ballweber-Fleming, Katharine G. Westerberg, Linh Mach, Tiffany Hensley-McBain, Laura Sutherland, et al. “Neutralization Takes Precedence Over IgG or IgA Isotype-related Functions in Mucosal HIV-1 Antibody-mediated Protection.EBioMedicine 14 (December 2016): 97–111. https://doi.org/10.1016/j.ebiom.2016.11.024.
Astronomo RD, Santra S, Ballweber-Fleming L, Westerberg KG, Mach L, Hensley-McBain T, et al. Neutralization Takes Precedence Over IgG or IgA Isotype-related Functions in Mucosal HIV-1 Antibody-mediated Protection. EBioMedicine. 2016 Dec;14:97–111.
Astronomo, Rena D., et al. “Neutralization Takes Precedence Over IgG or IgA Isotype-related Functions in Mucosal HIV-1 Antibody-mediated Protection.EBioMedicine, vol. 14, Dec. 2016, pp. 97–111. Pubmed, doi:10.1016/j.ebiom.2016.11.024.
Astronomo RD, Santra S, Ballweber-Fleming L, Westerberg KG, Mach L, Hensley-McBain T, Sutherland L, Mildenberg B, Morton G, Yates NL, Mize GJ, Pollara J, Hladik F, Ochsenbauer C, Denny TN, Warrier R, Rerks-Ngarm S, Pitisuttithum P, Nitayapan S, Kaewkungwal J, Ferrari G, Shaw GM, Xia S-M, Liao H-X, Montefiori DC, Tomaras GD, Haynes BF, McElrath JM. Neutralization Takes Precedence Over IgG or IgA Isotype-related Functions in Mucosal HIV-1 Antibody-mediated Protection. EBioMedicine. 2016 Dec;14:97–111.
Journal cover image

Published In

EBioMedicine

DOI

EISSN

2352-3964

Publication Date

December 2016

Volume

14

Start / End Page

97 / 111

Location

Netherlands

Related Subject Headings

  • Vagina
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • Neutralization Tests
  • Mucous Membrane
  • Macaca mulatta
  • Leukocytes
  • Immunophenotyping
  • Immunoglobulin G