biostudies-literatureMouwenda YDDZIFEuropean & Developing Countries Clinical Trials Partnership (EDCTP)NIAID NIH HHSDutch Research Council (NWO)NIHWISEe170210https://www.ebi.ac.uk/biostudies/studies/S-EPMC11141902biostudies-literatureUnknown9(9)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.JCI insightImmune responses associated with protection induced by chemoattenuated PfSPZ vaccine in malaria-naive Europeans.PMC11141902R44 AI058375U01 AI165745U01A1657455R44AI0552295R44AI058375SPI.2021.004DZIF TTU 03.802R44 AI055229RIA2018SV-2310PSIA2020AGDG-3316Betouke Ongwe MEFendel RMordmuller BEsen MStam KAMouwenda YDJochems SPYazdanbakhsh MMassinga Loembe MHoffman SLVan Unen VKremsner PGSim BKLde Steenhuijsen Piters WAAfalseImmune responses associated with protection induced by chemoattenuated PfSPZ vaccine in malaria-naive Europeans.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.2024-01-01T00:00:00Z2024 May2026-06-01T11:58:35.556Z2026-04-08T12:09:20.118ZS-EPMC111419023871673310.1172/jci.insight.170210