The malaria parasite Plasmodium vivax threatens half of the world's population. While on-going elimination efforts are successfully reducing the burden of falciparum malaria worldwide, the situation is much less promising for P. vivax. This discrepancy is partially due to our poor understanding of the biology of P. vivax that is difficult to study in the laboratory. Thus, a better understanding of the parasite proteins recognized by our immune system could guide vaccine development, enable more rigorous assessments of transmission and exposure, and allow the identification of individuals carrying dormant parasites. Unfortunately, analyses of the seroreactivity of P. vivax proteins have been limited to, at best, a few hundred proteins, and those typically derive from blood-stage parasites. We propose here to leverage extensive genomic and transcriptomic data generated by us and others to generate a comprehensive list of putative protein-coding transcripts expressed throughout the life cycle of the parasites. We will design and evaluate the seroreactivity of all those proteins using a high-density peptide array and serum samples that have been extensively characterized. Our studies will provide a comprehensive perspective on the P. vivax proteins recognized by the host during an infection, and constitute a solid foundation for identifying vaccine candidates and biomarkers for measuring exposure and transmission, as well as potentially, markers associated with the presence of dormant parasites in the liver.

Public Health Relevance

Understanding which parasite proteins are recognized by the host immune system is critical for designing efficient vaccines, measuring exposure and transmission, or for identifying individuals carrying dormant parasites. Unfortunately, for the human malaria parasite Plasmodium vivax only a few hundred proteins have been examined (out of 6,700 annotated protein-coding sequences). We propose to design and evaluate a high-density peptide arrays including overlapping peptides covering all annotated and putative P. vivax protein- coding sequences to comprehensively investigate the host antibody response to this important but understudied human pathogen.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI159307-01
Application #
10189044
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
O'Neil, Michael T
Project Start
2021-03-15
Project End
2023-02-28
Budget Start
2021-03-15
Budget End
2022-02-28
Support Year
1
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201