Repository of Monoclonal Antibodies (RoMA) against Hamster and Guinea Pig Proteins - Project Summary Small animal models are ideal to study diverse infectious and inflammatory diseases with mice being a widely used model system due to the well-characterized immune response and availability of reagents. Yet, the drawbacks of the mouse animal model are that it does not mimic many diseases due to the lack of clinical symptoms, differences in immune activation, and non-susceptible to infection of many pathogens. In fact, ferrets, Guinea pigs, and hamsters are a more suited animal model for numerous infectious pathogens including bat coronaviruses (SARS-CoV and SARS-CoV-2), influenza virus, and respiratory syncytial virus, respectively; yet, the lack of reagents that define the immune and inflammatory responses in ferrets, Guinea pigs, and hamsters prevent their utilization to comprehensively understand disease pathology and effectiveness of therapeutics and vaccines. Thus, there is a severe reagent gap for monoclonal antibodies against immune and inflammatory markers of ferrets, Guinea pigs, and hamsters to use these animal models in infectious disease studies. The main objective of the R24 application is to create a Repository of Monoclonal Antibodies (RoMA) for use in small animal models for evaluating infectious and inflammatory disorders fulfilling a major reagent gap in the scientific community. We hypothesize that reagents that monitor the immune response in hamster and Guinea pig model systems will be widely used in infectious disease model systems to predict disease progression and effectiveness of vaccines and therapeutics in human disease. A panel of monoclonal antibodies will be generated upon completion of the following aims: Aim 1: Develop antibodies targeting hamster and guinea pig surface markers on the respective immune cells. The hamster has become an excellent model for respiratory pathogens including SARS-corona viruses, Rift Valley fever, and Clostridium difficile; while the Guinea pig animal model provides insight into numerous infection and transmission models such as influenza virus and herpesviruses. Aim 2: Identify and generate monoclonal antibodies to hamster and guinea pig immune cell activation markers. We plan to identify and generate monoclonal antibodies to activated immune cell immune markers of hamster and Guinea pigs. These activated biomarkers will consist of previously characterized human and mouse orthologs that likely function in immune regulation. We expect to generate a total of 50 monoclonal antibodies (25 anti-hamster and 25 anti-Guinea pig proteins) over the 5-year grant period that will be available to the scientific community. These antibodies will be essential for evaluating the immune and inflammatory responses in the hamster and Guinea pig animal models.
