What it is
Whole-organism malaria vaccines made from liver-infective sporozoites give high levels of sterile protection against pre-erythrocytic (liver-stage) infection, but what makes the sporozoites immunogenic has been poorly characterized. Working in rodent models of vaccination, the authors show that the sporozoites' ability to actively migrate through several host cells before infecting liver cells (hepatocytes) is required for sterilizing immunity, however far the immunizing parasites develop inside the liver, and that this cell traversal is a dominant contributor to sterile protection. When traversal is impaired, vaccination no longer induces protective liver-resident memory CD8 T cell responses, although antiplasmodial antibodies are still produced.
Why it matters
A vaccine that confers sterile protection against Plasmodium, the parasite that causes malaria, is a major priority for global eradication efforts. The results show that the parasite's development inside the liver does not on its own account for how strong and durable whole-sporozoite vaccine protection is, and they point to parasite behaviour, here cell traversal, as a critical event in building sterilizing cellular immunity against the liver stages.
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Filed underMalaria Research and Control, Invertebrate Immune Response Mechanisms, Parasites and Host Interactions
