Immune responses associated with protection induced by chemoattenuated PfSPZ vaccine in malaria-naive Europeans

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Abstract
Vaccination of malaria-naive volunteers with a high dose of Plasmodium falciparum sporozoites chemoattenuated by chloroquine (CQ) (PfSPZ-CVac [CQ]) has previously demonstrated full protection against controlled human malaria infection (CHMI). However, lower doses of PfSPZ-CVac [CQ] resulted in incomplete protection. This provides the opportunity to understand the immune mechanisms needed for better vaccine-induced protection by comparing individuals who were protected with those not protected. Using mass cytometry, we characterized immune cell composition and responses of malaria-naive European volunteers who received either lower doses of PfSPZ-CVac [CQ], resulting in 50% protection irrespective of the dose, or a placebo vaccination, with everyone becoming infected following CHMI. Clusters of CD4 + and γδ T cells associated with protection were identified, consistent with their known role in malaria immunity. Additionally, EMRA CD8 + T cells and CD56 + CD8 + T cell clusters were associated with protection. In a cohort from a malaria-endemic area in Gabon, these CD8 + T cell clusters were also associated with parasitemia control in individuals with lifelong exposure to malaria. Upon stimulation with P . falciparum –infected erythrocytes, CD4 + , γδ, and EMRA CD8 + T cells produced IFN-γ and/or TNF, indicating their ability to mediate responses that eliminate malaria parasites.
Funding Information
  • WISE (PSIA2020AGDG-3316)
  • Norges Idrettshøgskole (5R44AI055229)
  • Norges Idrettshøgskole (5R44AI058375)
  • Norges Idrettshøgskole (U01A165745)
  • EDCTP2 (RIA2018SV-2310)
  • Deutsches Zentrum für Infektionsforschung (DZIF TTU 03.802)

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