{Reference Type}: Journal Article
{Title}: Immune responses associated with protection induced by chemoattenuated PfSPZ vaccine in malaria-naive Europeans.
{Author}: Mouwenda YD;Jochems SP;Van Unen V;Betouke Ongwe ME;de Steenhuijsen Piters WA;Stam KA;Massinga Loembe M;Sim BKL;Esen M;Hoffman SL;Kremsner PG;Fendel R;Mordmüller B;Yazdanbakhsh M;
{Journal}: JCI Insight
{Volume}: 9
{Issue}: 9
{Year}: 2024 May 8
{Factor}: 9.484
{DOI}: 10.1172/jci.insight.170210
{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.