Neutralizing antibody affords comparable protection against vaginal and rectal simian/human immunodeficiency virus challenge in macaques.

TitleNeutralizing antibody affords comparable protection against vaginal and rectal simian/human immunodeficiency virus challenge in macaques.
Publication TypeJournal Article
Year of Publication2016
AuthorsMoldt B, Le KM, Carnathan DG, Whitney JB, Schultz N, Lewis MG, Borducchi EN, Smith KM, Mackel JJ, Sweat SL, Hodges AP, Godzik A, Parren PWHI, Silvestri G, Barouch DH, Burton DR
JournalAIDS
Volume30
Issue10
Pagination1543-51
Date Published06/19/2016
ISSN1473-5571
Abstract

OBJECTIVE: Passive administration of broadly neutralizing antibodies has been shown to protect against both vaginal and rectal challenge in the simian/human immunodeficiency virus (SHIV)/macaque model of HIV transmission. However, the relative efficacy of antibody against the two modes of exposure is unknown and, given differences in the composition and immunology of the two tissue compartments, this is an important gap in knowledge. To investigate the significance of the challenge route for antibody-mediated protection, we performed a comparative protection study in macaques using the highly potent human monoclonal antibody, PGT126.

DESIGN: Animals were administered PGT126 at three different doses before challenged either vaginally or rectally with a single dose of SHIVSF163P3.

METHODS: Viral loads, PGT126 serum concentrations, and serum neutralizing titers were monitored.

RESULTS: In vaginally challenged animals, sterilizing immunity was achieved in all animals administered 10 mg/kg, in two of five animals administered 2 mg/kg and in one of five animals administered 0.4 mg/kg PGT126. Comparable protection was observed for the corresponding groups challenged rectally as sterilizing immunity was achieved in three of four animals administered 10 mg/kg, in two of four animals administered 2 mg/kg and in none of four animals administered 0.4 mg/kg PGT126. Serological analysis showed similar serum concentrations of PGT126 and serum neutralization titers in animals administered the same antibody dose.

CONCLUSION: Our data suggest that broadly neutralizing antibody-mediated protection is not strongly dependent on the mucosal route of challenge, which indicates that a vaccine aimed to induce a neutralizing antibody response would have broadly similar efficacy against both primary transmission routes for HIV.

DOI10.1097/QAD.0000000000001102
Alternate JournalAIDS
PubMed ID27243773
PubMed Central IDPMC4915739
Grant ListR37 AI055332 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
CHAVI-ID: 
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