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

• Authors: Brian Moldt, Scripps Research Institute; Khoa Le, Scripps Research Institute; Diane G. Carnathan, Emory University; James B Whitney, Harvard University; Niccole Schultz, Scripps Research Institute; Mark G. Lewis, Bioqual Inc; Erica Borducchi, Harvard University; Kaitlin Smith, Harvard University; Joseph J. Mackel, Emory University; Shelby L. Sweat, Emory University; Andrew P. Hodges, Sanford Burnham Prebys Medical Discovery Institute; Adam Godzik, Sanford Burnham Prebys Medical Discovery Institute; Paul W. H. I. Parren, Genmab; Guido Silvestri, Emory University; Dan H. Barouch, Harvard University; Dennis R. Burton, Scripps Research Institute
• Journal Title: AIDS
• Volume: Volume 30, Number 10
• Publisher: Lippincott, Williams & Wilkins | 2016-06-19, Pages 1543-1551
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1097/QAD.0000000000001102
• Subjects: Health Sciences, Immunology; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Infectious Diseases; Virology; HIV; mucosal transmission; neutralizing antibodies; vaccine; MUCOSAL SHIV CHALLENGE; PBL-SCID MICE; HUMAN MONOCLONAL-ANTIBODY; HIV-1/SIV CHIMERIC VIRUS; PASSIVE TRANSFER; IN-VITRO; IMPROVES PROTECTION; FC-RECEPTOR; INFECTION

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 SHIV SF163P3. 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.