Innate immune activation restricts priming and protective efficacy of the radiation-attenuated PfSPZ malaria vaccine.

ABSTRACT: A systems analysis was conducted to determine the potential molecular mechanisms underlying differential immunogenicity and protective efficacy results of a clinical trial of the radiation-attenuated whole-sporozoite PfSPZ vaccine in African infants. Innate immune activation and myeloid signatures at prevaccination baseline correlated with protection from P. falciparum parasitemia in placebo controls. These same signatures were associated with susceptibility to parasitemia among infants who received the highest and most protective PfSPZ vaccine dose. Machine learning identified spliceosome, proteosome, and resting DC signatures as prevaccination features predictive of protection after highest-dose PfSPZ vaccination, whereas baseline circumsporozoite protein-specific (CSP-specific) IgG pred

SUBMITTER: Senkpeil L 

PROVIDER: S-EPMC11382880 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature