Status: Funded - Closed
Naturally acquired T cell immune responses to novel malaria vaccine candidate, PfSEA-1
Christina Nixon, Ph.D.
BACKGROUND: P. falciparum is the greatest single-agent killer of children on the planet. In 2010, approximately 567,600 children less than 5 years old died from malaria in Africa alone making this disease responsible for one quarter of all childhood deaths.
GAP: Most human malaria vaccine trials currently underway are based on only 4 parasite antigens. For the eradication of malaria to be successful, identification of new immunogenic antigens is vital. The proposed studies will illuminate key aspects of the protective immune response to an exciting, novel vaccine candidate for P. falciparum, the most important parasitic disease of humans.
HYPOTHESIS: Schizont Egress Antigen-1 (PfSEA-1) is a newly identified, 244 kDa parasite antigen that is critical for parasite exit from an infected red blood cell. Naturally occurring antibodies to PfSEA-1 protect young children from severe malaria, and vaccination of mice with P. berghei SEA-1 protects against both parasitemia and mortality following P. berghei ANKA challenge. Based on preliminary studies, we hypothesize that PfSEA-1 will stimulate pro-inflammatory as well as Th1 cytokines from effector memory T cells in the majority of semi-immune children.
METHODS: The specific aim of this pilot study is to identify and characterize T cell immune responses in a cross-sectional sample of semi-immune children. This proposal is designed as a cross-sectional study in children (n=50; aged 9-12 years) residing in a holoendemic area of western Kenya to identify T cell responses to the immune-relevant region (rPfSEA-1A, aa 810-1083) of this critical parasite egress antigen, PfSEA-1.
IMPACT: The data generated from this project will advance a novel antigen, PfSEA-1, as a malaria vaccine candidate poised for testing within the context of a clinical trial against pediatric falciparum malaria.
Rhode Island Hospital
United States, United States, Kenya