Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo

Brian Moldt, Eva G. Rakasz, Niccole Schultz, Po Ying Chan-Hui, Kristine Swiderek, Kimberly L. Weisgrau, Shari M. Piaskowski, Zachary Bergman, David I. Watkins, Pascal Poignard, Dennis R. Burtona

Research output: Contribution to journalArticle

305 Scopus citations

Abstract

Most animal studies using passive administration of HIV broadly neutralizing monoclonal antibodies (bnMAbs) have associated protection against high-dose mucosal viral challenge with relatively high serum concentrations of antibody. We recently identified several bnMAbs remarkable for their in vitro potency against HIV. Of these bnMAbs, PGT121 is one of the most broad and potent antibodies isolated to date and shows 10- to 100-fold higher neutralizing activity than previously characterized bnMAbs. To evaluate the protective potency of PGT121 in vivo, we performed a protection study in rhesus macaques. Animals were i.v. administered 5 mg/kg, 1 mg/kg, or 0.2 mg/kg PGT121 24 h before being vaginally challenged with a single high dose of chimeric simian-human immunodeficiency virus (SHIV)SF162P3. Sterilizing immunity was achieved in all animals administered 5 mg/kg and 1 mg/kg and three of five animals administered 0.2 mg/kg PGT121, with corresponding average antibody serum concentrations of 95 μg/mL, 15 μg/mL, and 1.8 μg/mL, respectively. The results suggest that a protective serum concentration for PGT121 is in the single-digit μg/mL for SHIVSF162P3, showing that PGT121 can mediate sterilizing immunity at serum concentrations that are significantly lower than those observed in previous studies and that may be achievable through vaccination with the development of a suitable immunogen.

Original languageEnglish (US)
Pages (from-to)18921-18925
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number46
DOIs
StatePublished - Nov 13 2012

Keywords

  • Animal model
  • Antibody prophylaxis
  • Passive transfer

ASJC Scopus subject areas

  • General

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    Moldt, B., Rakasz, E. G., Schultz, N., Chan-Hui, P. Y., Swiderek, K., Weisgrau, K. L., Piaskowski, S. M., Bergman, Z., Watkins, D. I., Poignard, P., & Burtona, D. R. (2012). Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo. Proceedings of the National Academy of Sciences of the United States of America, 109(46), 18921-18925. https://doi.org/10.1073/pnas.1214785109