Research ArticleMalaria

Natural Immunization Against Malaria: Causal Prophylaxis with Antibiotics

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Science Translational Medicine  14 Jul 2010:
Vol. 2, Issue 40, pp. 40ra49
DOI: 10.1126/scitranslmed.3001058

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Needle-Free Vaccination for Malaria

Acquired through the bite of an infected mosquito, the malaria parasite continues to plague millions of people in the tropics, particularly in sub-Saharan Africa. Preventive methods directed at the mosquitoes, including bednets and insecticides, can be effective, but malaria remains a serious problem. Vaccination against malaria is a promising strategy because natural infections can sometimes confer protection against subsequent disease, showing that the parasite can be subdued immunologically, and there are numerous ongoing efforts. Here Friesen et al. report an approach that harnesses the antiparasitic power of the immune system in a different way. By administering antibiotics to mice early during infection, the authors both prevent later illness-causing stages of the parasite’s life-cycle and induce substantial immune protection against subsequent infection.

Once inside a host, the malaria parasite heads for the liver where it takes up residence, reproducing until the liver cells burst, releasing many mature pathogenic offspring that infect red blood cells. During this blood-stage infection, the damaging symptoms of malaria appear. If antibiotics are given to mice just after they are infected with the parasite, the shift from the liver-resident stage of the disease to the blood stage is prevented. Under these circumstances, the organisms mature normally in the liver and are released into the blood as usual (where they are called merosomes). These merosomes that form in the presence of antibiotics, however, are incapable of infecting red blood cells and cannot cause malaria symptoms such as anemia.

As if it weren’t enough to avoid blood-stage infection, the dumping of these ineffective parasites into the blood from liver cells—with their diverse antigens and large numbers—effectively inoculates the animal. Even after the antibiotic is completely gone from the animals’ system, it is protected from infection when injected with infectious parasites. Protection remains, even 6 months later. The authors then show that this immune defense is caused by interferon-γ–dependent CD8+ T cell responses.

These results are especially relevant because the antibiotics that the authors used, clindamycin and axithromycin, are known to be safe in children and pregnant women, criteria that would need to be met for any widely deployed malaria preventive strategy. Further indicating that this approach may be practical is the fact that very low doses of infecting parasite, such as one would receive naturally when living in a malaria-endemic area, can confer protection. Administration of antibiotics to people in the tropics could therefore confer protection by generating a natural “vaccination” with arrested malaria parasites.

Footnotes

  • Citation: J. Friesen, O. Silvie, E. D. Putrianti, J. C. R. Hafalla, K. Matuschewski, S. Borrmann, Natural immunization against malaria: Causal prophylaxis with antibiotics.Sci. Transl. Med. 2, 40ra49 (2010).

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