Protective CD8+ T-cell Immunity to Human Malaria Induced by Chimpanzee Adenovirus-MVA Immunisation

Overview

Journal Nat Commun

Specialty Biology

Date 2013 Nov 29

PMID 24284865

Citations 179

Authors

Katie J Ewer

Geraldine A OHara

Christopher J A Duncan

Katharine A Collins

Susanne H Sheehy

Arturo Reyes-Sandoval

Anna L Goodman

Nick J Edwards

Sean C Elias

Fenella D Halstead

Rhea J Longley

Rosalind Rowland

Ian D Poulton

Simon J Draper

Andrew M Blagborough

Eleanor Berrie

Sarah Moyle

Nicola Williams

Loredana Siani

Antonella Folgori

Stefano Colloca

Robert E Sinden

Alison M Lawrie

Riccardo Cortese

Sarah C Gilbert

Alfredo Nicosia

Adrian V S Hill

Affiliations

Soon will be listed here.

Abstract

Induction of antigen-specific CD8(+) T cells offers the prospect of immunization against many infectious diseases, but no subunit vaccine has induced CD8(+) T cells that correlate with efficacy in humans. Here we demonstrate that a replication-deficient chimpanzee adenovirus vector followed by a modified vaccinia virus Ankara booster induces exceptionally high frequency T-cell responses (median >2400 SFC/10(6) peripheral blood mononuclear cells) to the liver-stage Plasmodium falciparum malaria antigen ME-TRAP. It induces sterile protective efficacy against heterologous strain sporozoites in three vaccinees (3/14, 21%), and delays time to patency through substantial reduction of liver-stage parasite burden in five more (5/14, 36%), P=0.008 compared with controls. The frequency of monofunctional interferon-γ-producing CD8(+) T cells, but not antibodies, correlates with sterile protection and delay in time to patency (P(corrected)=0.005). Vaccine-induced CD8(+) T cells provide protection against human malaria, suggesting that a major limitation of previous vaccination approaches has been the insufficient magnitude of induced T cells.

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