Determinants of Malaria Protective Immunity in Mice Immunized with Live Sporozoites during Trimethoprim–Sulfamethoxazole Prophylaxis

Author:

Hobbs Charlotte V.123,Sahu Tejram34,Neal Jillian3,Conteh Solomon3,Voza Tatiana5,Borkowsky William6,Langhorne Jean7,Duffy Patrick E.3

Affiliation:

1. 1Division of Infectious Diseases, Department of Pediatrics, Batson Children’s Hospital, University of Mississippi Medical Center, Jackson, Mississippi;

2. 2Department of Microbiology, University of Mississippi Medical Center, Jackson, Mississippi;

3. 3Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland;

4. 4W. Harry Feinstone Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland;

5. 5Biological Sciences Department, New York City College of Technology, CUNY, New York, New York;

6. 6Division of Infectious Disease and Immunology, Department of Pediatrics, New York University School of Medicine, New York, New York;

7. 7The Francis Crick Institute, London, United Kingdom

Abstract

ABSTRACTHIV and malaria geographically overlap. Trimethoprim–sulfamethoxazole (TMP-SMX) is a drug widely used in HIV-exposed uninfected and infected children in malaria-endemic areas, and is known to have antimalarial effects. Further study in terms of antimalarial impact and effect on development of malaria-specific immunity is therefore essential. Using rodent malaria models, we previously showed that repeated Plasmodium exposure during TMP-SMX administration, or chemoprophylaxis vaccination (CVac), induces CD8 T-cell–dependent preerythrocytic immunity. However, humoral immune responses have been shown to be important in models of preerythrocytic immunity. Herein, we demonstrate that antibody-mediated responses contribute to protective immunity induced by CVac immune sera using TMP-SMX in models of homologous, but not heterologous, parasite species. Clinical studies must account for potential anti-Plasmodium antibody induced during TMP-SMX prophylaxis.

Publisher

American Society of Tropical Medicine and Hygiene

Subject

Virology,Infectious Diseases,Parasitology

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