Extreme genetic diversity in Plasmodium falciparum helps malaria parasites evade host immunity and impedes malaria vaccine development. Naturally acquired immunity to malaria is thought to represent the accumulation of protective immune responses to a repertoire of antigens and, importantly, to different variants of these antigens. But we remain largely ignorant of precisely which antigens and how many and which variants of these antigens must be recognized by which sorts of immune responses to afford natural or vaccine-induced protection. This project is largely focused on improving this understanding. Building on results of previous clinical translational research conducted in rural Mali, West Africa, we propose to further elucidate the mechanisms underlying both naturally acquired and vaccine-induced immune responses that protect against malaria infection and disease, and to use this knowledge to inform the development of broadly protective malaria vaccines. We will exploit recent technological advances to address at the genome-wide level questions that could previously be approached only one or a few genes at a time, developing new tools to assess immune responses against variant antigens and epitopes. In a prospective cohort study of children at risk for malaria infection and disease and in separate clinical trials of malaria vaccines, molecular and immunological correlates of natural and vaccine-induced protective immunity to P. falciparum infections and disease will be identified. This research is expected to provide information that will elucidate mechanisms underlying naturally acquired malaria immunity, improve the next generation of malaria vaccines and increase prospects for malaria elimination in Africa.

Public Health Relevance

Malaria parasites have evolved the ability to escape protective immune responses by varying the proteins that the immune system recognizes. This genetic diversity also makes it harder to develop a successful malaria vaccine. This project will study how changes in malaria genes and proteins relate to the risk of clinical malaria illness and to the ability of vaccines to prevent malaria. Study results are expected to provide information that will guide the development of effective malaria vaccines.

Agency
National Institute of Health (NIH)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI065683-10
Application #
8696753
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Rao, Malla R
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Coulibaly, Drissa; Travassos, Mark A; Kone, Abdoulaye K et al. (2014) Stable malaria incidence despite scaling up control strategies in a malaria vaccine-testing site in Mali. Malar J 13:374
Coulibaly, Drissa; Rebaudet, Stanislas; Travassos, Mark et al. (2013) Spatio-temporal analysis of malaria within a transmission season in Bandiagara, Mali. Malar J 12:82
Thera, Mahamadou A; Plowe, Christopher V (2012) Vaccines for malaria: how close are we? Annu Rev Med 63:345-57