An effective blood stage Plasmodium falciparum malaria vaccine would be of immense global health benefit, particularly for infants and young children who suffer the greatest burden of malaria morbidity and mortality. Our limited knowledge of vaccine-induced and naturally acquired correlates of immune protection represents a major impediment to the development of such a vaccine. Elucidating B cell epitopes may provide information needed for vaccine development. A high-density peptide microarray would provide the means to examine both the breadth and depth of antigenic diversity and the role of this diversity in the development of protective immunity that we wish to emulate with a vaccine. Furthermore, finer precision than what is currently available, and correspondingly detailed epitope mapping, will be possible through the creation a densely overlapping peptide array with full coverage of the falciparum proteome, a so-called peptidome. We propose to study naturally acquired and vaccine-induced immunity to malaria with novel peptide microarrays of 16-mer peptide sequences with the overall goals of identifying peptides that correlate with protection and informing malaria vaccine development. We will use a new technology that has been used successfully for a human peptidome to study human seroreactivity to parasite-derived peptides for the first time. We will create two arrays: 1) A diversity array will contain short flexible peptides that represent malaria vaccine candidate antigens and their diverse variants based on sequencing of malaria parasites from the field; and 2) A peptidome array will encompass all P. falciparum peptides corresponding to a well- characterized reference strain. These two arrays will provide the means for both fine epitope mapping and identification of naturally acquired and vaccine-induced correlates of protection. The corresponding antigens will be worthy of further study as potential vaccines. Knowledge gained from this project will enable the ultra-dense peptide array to be used to study the humoral immune response to other infectious organisms.

Public Health Relevance

Our limited knowledge of vaccine-induced and naturally acquired correlates of immune protection against malaria poses a critical barrier to the successful development of a malaria vaccine. This project seeks to identify specific malaria peptides that are targeted by antibodies that protect against both natural and experimentally-induced malaria in humans. Such correlates of protection help us to understand and predict natural and vaccine-induced protection, and to identify vaccine candidate antigens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI119733-02
Application #
9312736
Study Section
Vaccines Against Microbial Diseases Study Section (VMD)
Program Officer
MO, Annie X Y
Project Start
2016-07-07
Project End
2019-06-30
Budget Start
2017-07-01
Budget End
2019-06-30
Support Year
2
Fiscal Year
2017
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