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.