Pharmacokinetics and Preliminary Safety of Pod-Intravaginal Rings Delivering the Monoclonal Antibody VRC01-N for HIV Prophylaxis in a Macaque Model

• Type of Material: Article
• Authors: Chunxia Zhao, Emory University; Manjula Gunawardana, Oak Crest Institute of Science; Francois Villinger, Emory University; Marc M. Baum, Oak Crest Institute of Science; Mariana Remedios-Chan, Auritec Pharmaceut Inc; Thomas R. Moench, ReProtect Inc; Larry Zeitlin, Mapp Biopharmaceut Inc; Kevin J. Whaley, Mapp Biopharmaceut Inc; Ognian Bohorov, Mapp Biopharmaceut Inc; Thomas J. Smith, Auritec Pharmaceut Inc; Deborah J. Anderson, Boston University; John A. Moss, Oak Crest Institute of Science
• Language: English
• Date: 2017-07-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2017 American Society for Microbiology.
• Final Published Version (URL): http://dx.doi.org/10.1128/AAC.02465-16
• Title of Journal or Parent Work: Antimicrobial Agents and Chemotherapy
• ISSN: 0066-4804
• Volume: 61
• Issue: 7
• Start Page: e02465-16
• End Page: e02465-16
• Grant/Funding Information: This research was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number U19AI096398 and by the National Institutes of Health under award number P51OD11132 for support of the Yerkes National Primate Research Center.; We gratefully acknowledge their support.; The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
• Keywords: VAGINAL SHIV CHALLENGE; pharmacokinetics; BROADLY NEUTRALIZING ANTIBODIES; IMMUNODEFICIENCY-VIRUS TYPE-1; HIV prevention; VRC01; broadly neutralizing antibody; PREEXPOSURE PROPHYLAXIS; Pharmacology & Pharmacy; Science & Technology; intravaginal ring; Life Sciences & Biomedicine; SUSTAINED DELIVERY; human immunodeficiency virus; monoclonal antibody; CROSS-CLADE NEUTRALIZATION; PROXIMAL EXTERNAL REGION; TRANSMISSION; rhesus macaque model; NICOTIANA-BENTHAMIANA; drug delivery; Microbiology; AFRICAN WOMEN
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Pharmacology; Health Sciences, Immunology

Abstract

The broadly neutralizing antibody (bNAb) VRC01, capable of neutralizing 91% of known human immunodeficiency virus type 1 (HIV-1) isolates in vitro, is a promising candidate microbicide for preventing sexual HIV infection when administered topically to the vagina; however, accessibility to antibody-based prophylactic treatment by target populations in sub-Saharan Africa and other underdeveloped regions may be limited by the high cost of conventionally produced antibodies and the limited capacity to manufacture such antibodies. Intravaginal rings of the pod design (pod-IVRs) delivering Nicotiana-manufactured VRC01 (VRC01-N) over a range of release rates have been developed. The pharmacokinetics and preliminary safety of VRC01-N pod-IVRs were evaluated in a rhesus macaque model. The devices sustained VRC01-N release for up to 21 days at controlled rates, with mean steady-state VRC01-N levels in vaginal fluids in the range of 10 2 to 10 3 μg g -1 being correlated with in vitro release rates. No adverse safety indications were observed. These findings indicate that pod-IVRs are promising devices for the delivery of the candidate topical microbicide VRC01-N against HIV-1 infection and merit further preclinical evaluation.