Susceptibility to neutralization by broadly neutralizing antibodies generally correlates with infected cell binding for a panel of clade B HIV reactivated from latent reservoirs

Yanqin Ren, Maria Korom, Ronald Truong, Dora Chan, Szu Han Huang, Colin C. Kovacs, Erika Benko, Jeffrey T. Safrit, John Lee, Hermes Garbán, Richard Apps, Harris Goldstein, Rebecca M. Lynch, R. Brad Jones

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Efforts to cure human immunodeficiency virus (HIV) infection are obstructed by reservoirs of latently infected CD4 T cells that can reestablish viremia. HIV-specific broadly neutralizing antibodies (bNAbs), defined by unusually wide neutralization breadths against globally diverse viruses, may contribute to the elimination of these reservoirs by binding to reactivated cells, thus targeting them for immune clearance. However, the relationship between neutralization of reservoir isolates and binding to corresponding infected primary CD4 T cells has not been determined. Thus, the extent to which neutralization breadths and potencies can be used to infer the corresponding parameters of infected cell binding is currently unknown. We assessed the breadths and potencies of bNAbs against 36 viruses reactivated from peripheral blood CD4 T cells from antiretroviral (ARV)-treated HIV-infected individuals by using paired neutralization and infected cell binding assays. Single-antibody breadths ranged from 0 to 64% for neutralization (80% inhibitory concentration [IC 80 ] of 10 g/ml) and from 0 to 89% for binding, with two-antibody combinations (results for antibody combinations are theoretical/predicted) reaching levels of 0 to 83% and 50 to 100%, respectively. Infected cell binding correlated with virus neutralization for 10 of 14 antibodies (e.g., for 3BNC117, r 0.82 and P 0.0001). Heterogeneity was observed, however, with a lack of significant correlation for 2G12, CAP256.VRC26.25, 2F5, and 4E10. Our results provide guidance on the selection of bNAbs for interventional cure studies, both by providing a direct assessment of intra- and interindividual variabilities in neutralization and infected cell binding in a novel cohort and by defining the relationships between these parameters for a panel of bNAbs.

Original languageEnglish (US)
Article numbere00895
JournalJournal of virology
Volume92
Issue number23
DOIs
StatePublished - Jan 1 2018

Keywords

  • ADCC
  • Antibody-dependent cell cytotoxicity
  • BNAb
  • Broadly neutralizing antibody
  • Correlation
  • Human immunodeficiency virus
  • Infected cell binding
  • Neutralization

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Ren, Y., Korom, M., Truong, R., Chan, D., Huang, S. H., Kovacs, C. C., Benko, E., Safrit, J. T., Lee, J., Garbán, H., Apps, R., Goldstein, H., Lynch, R. M., & Brad Jones, R. (2018). Susceptibility to neutralization by broadly neutralizing antibodies generally correlates with infected cell binding for a panel of clade B HIV reactivated from latent reservoirs. Journal of virology, 92(23), [e00895]. https://doi.org/10.1128/JVI.00895-18