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

• 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
• Journal Title: Antimicrobial Agents and Chemotherapy
• Volume: Volume 61, Number 7
• Publisher: American Society for Microbiology | 2017-07-01, Pages e02465-16-e02465-16
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1128/AAC.02465-16
• Subjects: Health Sciences, Pharmacology; Health Sciences, Epidemiology; Health Sciences, Immunology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Microbiology; Pharmacology & Pharmacy; monoclonal antibody; broadly neutralizing antibody; VRC01; intravaginal ring; HIV prevention; drug delivery; rhesus macaque model; pharmacokinetics; human immunodeficiency virus; IMMUNODEFICIENCY-VIRUS TYPE-1; BROADLY NEUTRALIZING ANTIBODIES; CROSS-CLADE NEUTRALIZATION; PROXIMAL EXTERNAL REGION; VAGINAL SHIV CHALLENGE; PREEXPOSURE PROPHYLAXIS; SUSTAINED DELIVERY; NICOTIANA-BENTHAMIANA; AFRICAN WOMEN; TRANSMISSION

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.