title: Natural immunization against malaria: causal prophylaxis with antibiotics.
abstract: Malaria remains the most prevalent vector-borne infectious disease and has the highest rates of fatality. Current antimalarial drug strategies cure malaria or prevent infections but lack a sustained public health impact because they fail to expedite the acquisition of protective immunity. We show that antibiotic administration during transmission of the parasite Plasmodium berghei results in swift acquisition of long-lived, life cycle-specific protection against reinfection with live sporozoites in mice. Antibiotic treatment specifically inhibits the biogenesis and inheritance of the apicoplast in Plasmodium liver stages, resulting in continued liver-stage maturation but subsequent failure to establish blood-stage infection. Exponential expansion of these attenuated liver-stage merozoites from a single sporozoite induces potent immune protection against malaria. If confirmed in residents of malaria-endemic areas, periodic prophylaxis with safe and affordable antibiotics may offer a powerful shortcut toward a needle-free surrogate malaria immunization strategy.
authors.affiliation: Department of Infectious Diseases, Heidelberg University School of Medicine, 69120 Heidelberg, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Friesen
authors.forename: Olivier
authors.initials: O
authors.lastname: Silvie
authors.forename: Elyzana Dewi
authors.initials: ED
authors.lastname: Putrianti
authors.forename: Julius C R
authors.initials: JC
authors.lastname: Hafalla
authors.forename: Kai
authors.initials: K
authors.lastname: Matuschewski
authors.forename: Steffen
authors.initials: S
authors.lastname: Borrmann
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D017963:Azithromycin / Q000494:pharmacology / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002981:Clindamycin / Q000494:pharmacology / Q000627:therapeutic use; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology; D008018:Life Cycle Stages / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000469:parasitology; D008288:Malaria / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control*; D052940:Merozoites / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D051379:Mice; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D034101:Sporozoites / Q000166:cytology / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D002981:Clindamycin; D007371:Interferon-gamma; D017963:Azithromycin