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Principal Investigator: Joshua Tan
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2024
Award: $2,338,839
Funding agency: National Institute of Allergy and Infectious Diseases
The overarching goal of this project is to study the immune response to pathogens at the monoclonal level to increase our understanding of basic biology and develop new tools to combat disease. We are currently focusing our efforts on human monoclonal antibodies against three pathogens, Plasmodium falciparum, Mycobacterium tuberculosis, and SARS-CoV-2. The SARS-CoV-2 work is described in the accompanying report. For P. falciparum, we are examining antibodies against various stages of the life cycle, including sporozoites, blood stages and sexual stages. We are starting work on characterizing human antibodies against Mycobacterium tuberculosis.
In FY24, we investigated the antibody response to blood-stage P. falciparum, as well as to antigens on the sporozoite surface. In the blood stage project, we characterized monoclonal antibodies against the leading blood-stage vaccine candidate RH5. We compared antibodies isolated from individuals naturally exposed to malaria and those who were vaccinated with RH5 protein and adjuvant, identifying interesting similarities and differences between the two cohorts. These results suggest that natural infection may boost protective vaccine-derived antibody responses. We have just published a paper in Cell on this study. In another project, we identified unusual antibodies that do not bind to conventional sites on the sporozoite that show activity in an in vivo functional assay. We are in the process of studying the targets of these antibodies.
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