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Innate immune activation restricts priming and protective efficacy of the radiation-attenuated PfSPZ malaria vaccine.
Senkpeil, Leetah; Bhardwaj, Jyoti; Little, Morgan R; Holla, Prasida; Upadhye, Aditi; Fusco, Elizabeth M; Swanson, Phillip A; Wiegand, Ryan E; Macklin, Michael D; Bi, Kevin; Flynn, Barbara J; Yamamoto, Ayako; Gaskin, Erik L; Sather, D Noah; Oblak, Adrian L; Simpson, Edward; Gao, Hongyu; Haining, W Nicholas; Yates, Kathleen B; Liu, Xiaowen; Murshedkar, Tooba; Richie, Thomas L; Sim, B Kim Lee; Otieno, Kephas; Kariuki, Simon; Xuei, Xiaoling; Liu, Yunlong; Polidoro, Rafael B; Hoffman, Stephen L; Oneko, Martina; Steinhardt, Laura C; Schmidt, Nathan W; Seder, Robert A; Tran, Tuan M.
Afiliação
  • Senkpeil L; Division of Infectious Diseases, Department of Medicine.
  • Bhardwaj J; Department of Microbiology and Immunology, and.
  • Little MR; Division of Infectious Diseases, Department of Medicine.
  • 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; Ryan White Center for Pediatric Infectious Diseases and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • Fusco EM; Division of Infectious Diseases, Department of Medicine.
  • Swanson PA; Department of Microbiology and Immunology, and.
  • Wiegand RE; Cellular Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA.
  • Macklin MD; Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
  • Bi K; Division of Infectious Diseases, Department of Medicine.
  • Flynn BJ; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Yamamoto A; Cellular Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA.
  • Gaskin EL; Cellular Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA.
  • Sather DN; Division of Infectious Diseases, Department of Medicine.
  • Oblak AL; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, Washington, USA.
  • Simpson E; Stark Neurosciences Research Institute and.
  • Gao H; Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • Haining WN; Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • Yates KB; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
  • Liu X; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  • Murshedkar T; Deming Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana, USA.
  • Richie TL; Sanaria, Rockville, Maryland, USA.
  • Sim BKL; Sanaria, Rockville, Maryland, USA.
  • Otieno K; Sanaria, Rockville, Maryland, USA.
  • Kariuki S; Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya.
  • Xuei X; Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya.
  • Liu Y; Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • Polidoro RB; Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • Hoffman SL; Ryan White Center for Pediatric Infectious Diseases and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • Oneko M; Sanaria, Rockville, Maryland, USA.
  • Steinhardt LC; Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya.
  • Schmidt NW; Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
  • Seder RA; Department of Microbiology and Immunology, and.
  • Tran TM; Ryan White Center for Pediatric Infectious Diseases and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
JCI Insight ; 9(11)2024 Apr 30.
Article em En | MEDLINE | ID: mdl-38687615
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 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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Plasmodium falciparum / Vacinas Atenuadas / Malária Falciparum / Vacinas Antimaláricas / Esporozoítos / Imunidade Inata Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Plasmodium falciparum / Vacinas Atenuadas / Malária Falciparum / Vacinas Antimaláricas / Esporozoítos / Imunidade Inata Idioma: En Ano de publicação: 2024 Tipo de documento: Article