Mechanisms of Stage-Transcending Protection Following Immunization of Mice with Late Liver Stage-Arresting Genetically Attenuated Malaria Parasites

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Malaria is arguably one of the deadliest infectious diseases in human history. Today, it infects nearly 300 million people each year and kills up to 1 million of those—mostly women and children under the age of 5—and no effective malaria vaccine has been developed. Traditional subunit vaccines for pathogens work by training the immune system to recognize a single pathogen target. Attempts at developing a subunit malaria vaccine have, however, been stymied by the complexity of the parasite genome which encodes a complex life cycle with specific stages in the mosquito, as well as in the liver and blood of the mammalian host. Only the blood stage parasites cause malaria symptoms and mortality. Previously, it was assumed that immunity to malaria is stage-specific, either targeting parasites in the liver or in blood, but not both. The herein described vaccination approach uses genetically engineered, attenuated rodent malaria parasites that are able to infect the mouse liver and replicate, but die shortly before red blood-infectious parasite stages are formed and released. Immunization with these attenuated parasites induces the immune system to build defenses against both parasite stages in the liver and blood. Protection is mediated by multiple arms of the immune system. The antibody arm recognizes parasite targets shared between liver stages and blood stages. This not only demonstrates the optimal potency of this live-attenuated vaccination strategy, but also provides a potential source of new malaria subunit vaccine targets.

Vyšlo v časopise: Mechanisms of Stage-Transcending Protection Following Immunization of Mice with Late Liver Stage-Arresting Genetically Attenuated Malaria Parasites. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004855
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004855

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