1. Trimethoprim-Sulfamethoxazole Prophylaxis During Live Malaria Sporozoite Immunization Induces Long-Lived, Homologous, and Heterologous Protective Immunity Against Sporozoite Challenge
- Author
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Tatiana Voza, Solomon Conteh, William Borkowsky, Jean Langhorne, Patrick E. Duffy, Charles Anderson, Charlotte V. Hobbs, Jillian Neal, and Tejram Sahu
- Subjects
0301 basic medicine ,Male ,Plasmodium ,Opportunistic infection ,030106 microbiology ,Heterologous ,HIV Infections ,CD8-Positive T-Lymphocytes ,Opportunistic Infections ,urologic and male genital diseases ,03 medical and health sciences ,Major Articles and Brief Reports ,Antimalarials ,Interferon-gamma ,Mice ,Immunity ,parasitic diseases ,Trimethoprim, Sulfamethoxazole Drug Combination ,medicine ,Immunology and Allergy ,Animals ,Mice, Knockout ,Life Cycle Stages ,Mice, Inbred BALB C ,business.industry ,Sulfamethoxazole ,medicine.disease ,bacterial infections and mycoses ,Trimethoprim ,Virology ,female genital diseases and pregnancy complications ,Malaria ,Vaccination ,Infectious Diseases ,Immunization ,Sporozoites ,Immunology ,business ,medicine.drug - Abstract
Trimethoprim-sulfamethoxazole (TMP-SMX) is widely used in malaria-endemic areas in human immunodeficiency virus (HIV)-infected children and HIV-uninfected, HIV-exposed children as opportunistic infection prophylaxis. Despite the known effects that TMP-SMX has in reducing clinical malaria, its impact on development of malaria-specific immunity in these children remains poorly understood. Using rodent malaria models, we previously showed that TMP-SMX, at prophylactic doses, can arrest liver stage development of malaria parasites and speculated that TMP-SMX prophylaxis during repeated malaria exposures would induce protective long-lived sterile immunity targeting pre-erythrocytic stage parasites in mice. Using the same models, we now demonstrate that repeated exposures to malaria parasites during TMP-SMX administration induces stage-specific and long-lived pre-erythrocytic protective anti-malarial immunity, mediated primarily by CD8+ T-cells. Given the HIV infection and malaria coepidemic in sub-Saharan Africa, clinical studies aimed at determining the optimum duration of TMP-SMX prophylaxis in HIV-infected or HIV-exposed children must account for the potential anti-infection immunity effect of TMP-SMX prophylaxis.
- Published
- 2016