Molecular Hallmarks of Naturally Acquired Immunity to Malaria

Summary

Malaria, caused by P. falciparum, remains a major public health threat. Over 500 million cases of malaria occur annually among the world's poorest populations, claiming the lives of nearly a million children each year in Africa alone. Ultimately, a key tool for the control or elimination of malaria, in addition to anti-malarial drugs and vector control, is an effective vaccine. The development of a highly effective malaria vaccine has been hindered by the sheer complexity of the parasite and its life cycle, and a poor understanding of the interaction between P. falciparum and the human immune system. The premise of this project is that an improved understanding of the human immune response to P. falciparum infection may increase the probability of developing a highly effective malaria vaccine.

The current study will apply genomic analyses to individuals (between 3 months and 25 years of age) from a rural village of Kalifabougou, Mali, where P. falciparum transmission is intense and seasonal. Asymptomatic P. falciparum infection and malaria episodes will be detected by passive and active surveillance. Genomic, transcriptomic and metagenomic features of malaria-protected and -susceptible individuals will be derived from blood and stool samples collected at strategic time points before, during and after P. falciparum infection. Signatures that correlate with protection from malaria may yield new hypotheses regarding the biological mechanisms through which malaria immunity is induced by natural P. falciparum infection.

The project aims to identify human gene expression profiles and genotypes that are associated with immunity to malaria in a cohort of 700 subjects from the village. The gut microbiota from up to 200 of these individuals will also be analyzed. In addition to the genomic and transcriptomic data that will be generated, each subject will provide a wide range of demographic, clinical and immunological data that will be incorporated into the analysis. These data include a medical history, pregnancy status, hemoglobin typing, composition of leukocyte subpopulations, IgG reactivity against P. falciparum proteins, levels of serum cytokines and chemokines, and infection status for Plasmodium species, intestinal helminths, and common respiratory viruses.

The primary endpoints of the project are:

  • To compare P. falciparum-induced genome-wide expression profiles in malaria-susceptible and malaria-immune individuals.
  • To compare genotypes at targeted genomic loci in age-matched malaria-susceptible and malaria-immune individuals.
  • To compare the gut microbiome of malaria-susceptible and malaria-immune individuals, and identify any association with immunological responses.

Project Director:

Dr. Hernan Lorenzi Profile Dr. Hernan Lorenzi, Project Director, Assistant Professor

Citations

All Publications that use data generated and/or are supported by the Sequencing Center at JCVI should acknowledge the sponsor as below:

"Research reported in this publication was supported by the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health under Award Number U19AI110819. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health."