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

Autor: Senkpeil L; Division of Infectious Diseases, Department of Medicine.; Department of Microbiology and Immunology, and., Bhardwaj J; Division of Infectious Diseases, Department of Medicine., Little MR; Ryan White Center for Pediatric Infectious Diseases and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA., Holla P; Ryan White Center for Pediatric Infectious Diseases and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA., Upadhye A; Division of Infectious Diseases, Department of Medicine., Fusco EM; Department of Microbiology and Immunology, and., Swanson PA 2nd; Cellular Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA., Wiegand RE; Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA., Macklin MD; Division of Infectious Diseases, Department of Medicine., Bi K; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA., Flynn BJ; Cellular Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA., Yamamoto A; Cellular Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA., Gaskin EL; Division of Infectious Diseases, Department of Medicine., Sather DN; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA., Oblak AL; Stark Neurosciences Research Institute and., Simpson E; Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, Indiana, USA., Gao H; Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, Indiana, USA., Haining WN; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA., Yates KB; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA., Liu X; Deming Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA., Murshedkar T; Sanaria, Rockville, Maryland, USA., Richie TL; Sanaria, Rockville, Maryland, USA., Sim BKL; Sanaria, Rockville, Maryland, USA., Otieno K; Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya., Kariuki S; Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya., Xuei X; Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, Indiana, USA., Liu Y; Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, Indiana, USA., Polidoro RB; Ryan White Center for Pediatric Infectious Diseases and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA., Hoffman SL; Sanaria, Rockville, Maryland, USA., Oneko M; Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya., Steinhardt LC; Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA., Schmidt NW; Department of Microbiology and Immunology, and.; Ryan White Center for Pediatric Infectious Diseases and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA., Seder RA; Cellular Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA., Tran TM; Division of Infectious Diseases, Department of Medicine.; Department of Microbiology and Immunology, and.; Ryan White Center for Pediatric Infectious Diseases and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Jazyk: angličtina
Zdroj: JCI insight [JCI Insight] 2024 Apr 30; Vol. 9 (11). Date of Electronic Publication: 2024 Apr 30.
DOI: 10.1172/jci.insight.167408
Abstrakt: 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 predicted nonprotection. Prevaccination innate inflammatory and myeloid signatures were associated with higher sporozoite-specific IgG Ab response but undetectable PfSPZ-specific CD8+ T cell responses after vaccination. Consistent with these human data, innate stimulation in vivo conferred protection against infection by sporozoite injection in malaria-naive mice while diminishing the CD8+ T cell response to radiation-attenuated sporozoites. These data suggest a dichotomous role of innate stimulation for malaria protection and induction of protective immunity by whole-sporozoite malaria vaccines. The uncoupling of vaccine-induced protective immunity achieved by Abs from more protective CD8+ T cell responses suggests that PfSPZ vaccine efficacy in malaria-endemic settings may be constrained by opposing antigen presentation pathways.
Databáze: MEDLINE
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