Preclinical Core

Weill Medical Coll Of Cornell Univ, New York NY

Investigators

Abstract

ABSTRACT – PRECLINICAL CORE Achieving an end to the HIV/AIDS epidemic hinges on developing an effective vaccine regimen that provides long-term protective immunity prior to adolescence. Unlike existing platforms, current HIV vaccine candidates have struggled to elicit highly protective immunity in adults. Intriguingly, recent studies suggest that durable and potent immune responses may be more attainable in infancy. This P01 Program focuses on utilizing nonhuman primate (NHP) models, mirroring human development, to establish the safety, feasibility, and optimal regimen of a broadly-neutralizing antibody (bnAb)-targeting HIV vaccination in early life. We hypothesize and will test if, leveraging the immunologic advantages of the early life immune landscape, administering germline-targeting SOSIP vaccine regimens at optimal dose and intervals during early life results in efficient HIV bnAb B cell lineage induction, informing human clinical trial design and a clinical licensure pathway. Towards this goal our Core will perform the necessary preclinical vaccine studies in an infant macaque model that will establish the safety and optimal dose and intervals (Project 1) and immunologic impact of maternal antibodies and other childhood vaccines (Project 2). The Preclinical Core is an integral component of the overall Program and provides direct support to the Projects by coordinating and implementing all the NHP experiments including regulatory approvals, immunizations, sample collections and vaccine and antibody safety assessments. Utilizing the resources at the California National Primate Research Center's (CNPRC), the Preclinical Core will collaborate with program investigators to ensure comprehensive experimental support. CNPRC's resources include a large rhesus macaque breeding colony, expertise in infant macaque care and models with SHIV infection, and all necessary procedures for monitoring and sample collection essential for the Program's success. Projects within the Program investigate the optimal and safest dose, interval, and adjuvants of early life BG505 GT1.1 SOSIP trimer immunization for inducing bnAb precursor B cell lineages, as well as the safety and impact of passive administration with HIV bnAbs. The expertise of the Preclinical Core, combined with CNPRC's infrastructure, positions this program at the forefront of preclinical to clinical HIV vaccine research.