Malaria News |
Extreme CD8 T Cell Requirements for Anti-Malarial Liver-Stage Immunity following Immunization with Radiation Attenuated Sporozoites 
Plasmodium infections are a global health crisis resulting in ~300 million cases of malaria each year and ~1 million deaths. Radiation-attenuated Plasmodium sporozoites (RAS) are the only vaccines that induce sterilizing anti-malarial immunity in humans. Importantly, "whole parasite" anti-malarial RAS vaccines are currently under evaluation in clinical trials. In rodents, RAS-induced protection is largely mediated by CD8 T cells. However, the quantitative and qualitative characteristics of RAS-induced protective CD8 T cell responses are unknown. Here, we used surrogate markers of T cell activation to reveal the magnitude and kinetics of Plasmodium-specific CD8 T cell responses following RAS-immunization in both inbred and outbred mice. Our data show that, independent of host genetic background, extremely large memory CD8 T cell responses were required, but not always sufficient for sterilizing protection. These data have broad implications for evaluating total T cell responses to attenuated pathogen-vaccines and direct relevance for efforts to translate attenuated whole-Plasmodium vaccines to humans.
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