Antibody Discovery for Non-Human Coronaviruses with the Potential for Human Emergence
Abstract
Antibodies – protein molecules that are derived from the immune system – are effectively used in diagnostics, therapy, and prevention against numerous diseases, such as infectious disease, cancer, autoimmunity, and others. A paramount feature of antibodies is the typically exquisite specificity that they possess against their targets (referred to as antigens). Over the last several decades, antibody discovery efforts have met with notable success, resulting in the approval of numerous effective antibody-based clinical products. However, to date, antibody discovery efforts have focused on identifying antibodies against pathogens that have already crossed into humans, focusing primarily on samples (such as blood) with prior exposure (through infection or vaccination) to these pathogens. In the case of SARS-CoV-2, even though effective monoclonal antibodies and vaccines were discovered and validated within months, the COVID-19 pandemic still has had a devastating effect, resulting in the loss of millions of human lives, extreme potentially long-lasting burden on the health care system, and economic turmoil. Therefore, the preemptive development of countermeasures against a diversity of pathogens, even ones that have not yet crossed into humans – and especially before they have crossed into humans – is of utmost significance. To address this challenge, here we propose to develop a program for the discovery of countermeasures against a broad diversity of coronaviruses, specifically focusing on coronaviruses that have not yet emerged in humans. Current pandemic preparedness approaches focus on antibody discovery against human pathogens. The goal of such approaches is to generate a repository of antibodies as countermeasures for future significant outbreaks of pathogens that are already observed in the human population but that are currently with lower frequency of occurrence, restricted to specific geographic regions, and/or have limited public health burden. However, in the general case, these pandemic preparedness approaches will not be able to prepare us against pathogens that are yet to emerge in humans. Hence, in this project, we will aim to develop a platform for the high-throughput discovery of antibodies against non-human pathogens with the potential for human emergence. Our proposed efforts fall within the Viral Diseases Fiscal Year 2022 (FY22) Peer Reviewed Medical Research Program (PRMRP) Topic Area, with a focus on the following FY22 PRMRP Strategic Goal: Develop or optimize vaccine strategies, platforms, or compounds, to include active or passive immunoprophylaxis, especially for Dengue, Lassa, and Crimean-Congo Hemorrhagic fever viruses, beta-coronaviruses. As an initial focus of our efforts, we will target the development of this platform in the context of coronaviruses, a family of pathogens with clear potential for future pandemics. In particular, we will focus on the discovery and characterization of antibodies against a wide range of non-human coronaviruses, as potential therapeutic candidates and templates for broadly protective vaccines, should any of these coronaviruses emerge into humans in the future. A critical advantage of our efforts is our recently developed LIBRA-seq technology (LInking B-cell Receptor to Antigen specificity through sequencing) for antibody discovery and characterization of antigen-specific monoclonal antibodies. Unlike other antibody discovery approaches, LIBRA-seq is unique in its ability to simultaneously screen candidate antibodies against a theoretically unlimited set of targets. LIBRA-seq therefore provides a unique opportunity for screening for antigen-specific antibodies that are capable of recognizing a wide range of coronaviruses. Overall, the discovery of antibodies against diverse coronaviruses will become a first line of defense against new outbreaks with previously unencountered coronaviruses, if (and when) these coronaviruses emerge in humans. Further, the anti
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310070
Entities
People
- Ivelin Georgiev
Organizations
- United States Army
- Vanderbilt University