Thursday, May 19, 2022
5/19/2022
Project Summary Malaria is still responsible for an estimated 429,000 deaths and 212 million infections per year, the large majority among young children. Individuals living in endemic regions gradually develop an immune response that protects against symptomatic disease. Naturally acquired immunity targets the blood stage of the parasite’s life cycle and is largely dependent on antibody reactivity. Studies of naturally acquired immunity suggest that protected individuals harbor antibodies against conserved epitopes. The identification of such conserved epitopes could serve as a blueprint for structure-based design of a malaria blood stage vaccine. The parent grant (R01 AI153425) aims to test the central hypothesis that immunity against malaria is dependent on high affinity IgGs with cross-strain reactivity against merozoite antigens and that these antibodies can be used to define conserved epitopes on merozoite vaccine candidates. The objectives of this current proposal, which is submitted in response to the opportunity “Research Supplement to Promote Diversity in Health-Related Research (PA-21- 071)”, are first, to promote diversity in health-related research by training Mr. Rolando Garza, an M.D./Ph.D. student from a background underrepresented in biomedical sciences, and second, to extend the parent application by studying B cell responses to a novel vaccine candidate, PF3D7_1136200. We hypothesize that cross-strain reactive, PF3D7_1136200-specific antibodies inhibit P. falciparum growth in vitro, and, in part, mediate protection from symptomatic malaria. This hypothesis will be tested by two related yet independent aims. In Supplemental Aim 1, we will isolate PF3D7_1136200-specific memory B cells from malaria-experienced children and adults and test the ability of monoclonal antibodies obtained from these B cells to inhibit various malaria parasite strains in vitro. In Supplemental Aim 2, we will quantify the number of PF3D7_1136200-specific memory B cells and determine their phenotype using high-parameter spectral flow cytometry. The proposed study will promote diversity in health-related research, since an M.D./Ph.D. student from a background underrepresented in bio-medical sciences will be one of main beneficiaries of this study. Additionally, this study provides an outstanding training opportunity, since it will allow Mr. Garza to acquire competency in all areas required for a successful career as an independent investigator and physician scientist, including technical skills, data analysis, critical thinking, presentation and publication of research findings, professional development, and project management.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
