Protective Immunity Induced with Malaria Vaccine, RTS,S, Is Linked to <i>Plasmodium falciparum</i> Circumsporozoite Protein-Specific CD4+ and CD8+ T Cells Producing IFN-γ

TLDR

RTS,S, a circumsporozoite protein–based pre‑erythrocytic malaria vaccine, protects against experimental sporozoite challenge, yet the underlying immune mechanisms—presumed to involve antibodies and T‑cell responses—remain only partially understood and are being examined in field studies to validate cellular responses as correlates of protection. The study compared CS peptide‑induced IFN‑γ responses of lymphocytes from 20 RTS,S‑vaccinated subjects to assess vaccine‑induced cellular immunity. Protected subjects exhibited higher CS‑peptide‑induced IFN‑γ, with both CD4+ and CD8+ T cells contributing, and sustained IFN‑γ responses correlated with prolonged protection in a subset, marking the first controlled study linking vaccine‑induced protection to antigen‑specific T‑cell activity.

Abstract

Abstract The Plasmodium falciparum circumsporozoite (CS) protein-based pre-erythrocytic stage vaccine, RTS,S, induces a high level of protection against experimental sporozoite challenge. The immune mechanisms that constitute protection are only partially understood, but are presumed to rely on Abs and T cell responses. In the present study we compared CS protein peptide-recalled IFN-γ reactivity of pre- and RTS,S-immune lymphocytes from 20 subjects vaccinated with RTS,S. We observed elevated IFN-γ in subjects protected by RTS,S; moreover, both CD4+ and CD8+ T cells produced IFN-γ in response to CS protein peptides. Significantly, protracted protection, albeit observed only in two of seven subjects, was associated with sustained IFN-γ response. This is the first study demonstrating correlation in a controlled Plasmodia sporozoite challenge study between protection induced by a recombinant malaria vaccine and Ag-specific T cell responses. Field-based malaria vaccine studies are in progress to validate the establishment of this cellular response as a possible in vitro correlate of protective immunity to exo-erythrocytic stage malaria vaccines.