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

TitleHighly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo.
Publication TypeJournal Article
Year of Publication2012
AuthorsMoldt B, Rakasz EG, Schultz N, Chan-Hui P-Y, Swiderek K, Weisgrau KL, Piaskowski SM, Bergman Z, Watkins DI, Poignard P, Burton DR
JournalProc Natl Acad Sci U S A
Volume109
Issue46
Pagination18921-5
Date Published11/13/2012
ISSN1091-6490
KeywordsAnimals, Antibodies, Monoclonal, Antibodies, Neutralizing, Female, HIV Antibodies, HIV Infections, HIV-1, Humans, Immunization, Passive, Macaca mulatta
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 SHIV(SF162P3), 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.

DOI10.1073/pnas.1214785109
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID23100539
PubMed Central IDPMC3503218
Grant ListR01 AI33292 / AI / NIAID NIH HHS / United States
U19AI090970 / AI / NIAID NIH HHS / United States
UM1AI100663 / AI / NIAID NIH HHS / United States
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