Nonhuman Primate Antibody Resource for Immune Cell Depletion

Univ Of Massachusetts Med Sch Worcester, Worcester MA

Investigators

Linked publications & trials

Abstract

Project Summary – Overall Nonhuman primates (NHPs) have historically served as crucial animal models for diseases and for testing new therapies and vaccines that cannot be evaluated in small animal models. The utility of NHP models in research has been enhanced considerably by the use of immune cell-depleting antibodies that can target and lyse specific cell subsets in vivo. In models of infectious disease and vaccine testing, targeted immune cell depletion has been used to understand the pathogenesis of these infections and to design better vaccines to prevent them. Furthermore, immune cell depletion can be an effective immune-modulating therapy and the preclinical testing of these cell-depleting antibody drugs is often conducted in NHPs. Our P40-funded Center, “Nonhuman Primate Antibody Resource for Immune Cell Depletion,” has been a major source of immune cell-depleting antibodies for the scientific community, and our vital reagents have enabled NHP studies in fundamental, biomedical, and preclinical research. For the past 24 years, NIH has supported the Nonhuman Primate Reagent Resource’s efforts to develop, characterize, manufacture, and distribute immune cell-depleting antibodies for use in NHP models through an R24, which was then superseded by this and a P40 grant. The need for this program has been confirmed by the growth in program activity since its inception. Over the past 5-year cycle (2018-2022), this grant fulfilled 547 reagent requests to 139 investigators from 95 institutions. These reagents were cited in 73 publications and supported 226 NIH grants or programs. Nearly 1.16 kilograms of 14 distinct antibody reagents were distributed. In this P40 renewal, we propose to continue to support the scientific community by maintaining the large-scale manufacture and quality control of immune cell-depleting and control antibodies for use in NHPs. We will also develop and optimize antibodies against new high-priority NHP targets identified by the scientific community, via our outreach strategy and development request web portal tools. The reagent development will be prioritized by our External Advisory Board. Our established, secure web-based infrastructure will continue to be used for advertising reagents, receiving and fulfilling requests, and measuring program effectiveness through surveys and an interactive dashboard. In the proposed funding cycle, we will institute a new Curation and Informatics Component that will be dedicated to curating, tracking, distributing, and promoting the Center’s reagents. The Curation and Informatics Component will also be responsible for maintaining and upgrading the web portal to increase our alignment with FAIR and TRUST guidelines. Our vision is that our Center will not only generate invaluable reagents but will also enhance rigor and transparency in the use of our reagents to improve reproducibility. Finally, we will conduct applied research to develop a new antibody ‘primatization’ method to improve the performance of our depletion therapies in NHP studies. This award funds unique NHP cell-depleting antibodies that are indispensable tools to hundreds of NIH grants.