Artikel
Single immunization with live sporozoites under chemoprophylaxis induces protection against experimental cerebral malaria
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Veröffentlicht: | 17. Dezember 2014 |
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Gliederung
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Background and aims: 77% of the deaths caused by malaria in 2012 occurred in the group of children under 5 years and mainly in sub-Saharan Africa. Young, non-semi immune children are at major risk to develop cerebral symptoms and to die from severe malaria. Vaccination with live sporozoites under chemoprophylaxis can induce sterile protection against malaria but needs to be administered intravenously on three to five occasions. The intention of our study in the rodent model was to evaluate if a single, ideally non-intravenous immunization could be sufficient to induce semi-immunity represented by protection against experimental cerebral malaria (ECM).
Methods: Inbred C57BL/6 mice received a single intravenous or subcutaneous immunization with live Plasmodium berghei ANKA wild-type sporozoites (Pb WT SPZ) under chemoprophylaxis with either Chloroquine or Piperaquine. Mice were challenged 6 or 12 weeks after immunization with 1,000 Pb WT SPZ injected intravenously. The ECM-free survival was evaluated. Blood smears were carried out to investigate prepatency and parasitemia. The immune response was characterized through Flow Cytometry T lymphocyte subset analysis and in-vivo imaging of parasite liver load in mice.
Results: Immunized mice were completely protected against ECM. There was no significant reduction in parasite liver load of immunized mice but detection of blood-stage infection was delayed by one day in comparison to non-immunized naïve and drug treated control animals.
Conclusion: A single subcutaneous immunization with live SPZ under chemoprophylaxis induces protection against ECM. This simplified immunization schedule might be a feasible approach to reduce malaria mortality in children living in high-transmission settings.