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

JCI Insight. 2024 May 8;9(9):e170210. 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.

Keywords: Cellular immune response; Cytokines; Immunology; Malaria; Vaccines.

Publication types

  • Research Support, Non-U.S. Gov't
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Antimalarials / administration & dosage
  • Antimalarials / therapeutic use
  • CD4-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes* / immunology
  • Central African People
  • Chloroquine / pharmacology
  • Chloroquine / therapeutic use
  • Europe
  • European People
  • Female
  • Gabon
  • Humans
  • Malaria Vaccines* / administration & dosage
  • Malaria Vaccines* / immunology
  • Malaria, Falciparum* / immunology
  • Malaria, Falciparum* / prevention & control
  • Male
  • Parasitemia / immunology
  • Plasmodium falciparum* / immunology
  • Sporozoites* / immunology
  • Vaccination / methods
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / immunology
  • Young Adult

Substances

  • Antimalarials
  • Chloroquine
  • Malaria Vaccines
  • Vaccines, Attenuated