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J Infect Dis. 2015 Apr 1;211(7):1076-86. doi: 10.1093/infdis/jiu579. Epub 2014 Oct 21.

Evaluation of the efficacy of ChAd63-MVA vectored vaccines expressing circumsporozoite protein and ME-TRAP against controlled human malaria infection in malaria-naive individuals.

Author information

1
Jenner Institute.
2
Jenner Institute Royal College of Surgeons in Ireland, Dublin, Ireland.
3
NIHR Wellcome Trust Clinical Research Facility, University of Southampton and University Hospital Southampton NHS Foundation Trust.
4
Centre for Statistics in Medicine.
5
Clinical Biomanufacturing Facility, University of Oxford.
6
Okairos, Rome.
7
Okairos, Basel, Switzerland.
8
Jenner Institute Division of Cell and Molecular Biology, Imperial College London, United Kingdom.
9
Centre for Geographical Medical Research (Coast), Kenya Medical Research Institute-Wellcome Trust, Kilifi.
10
Okairos, Rome CEINGE Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Italy.

Abstract

BACKGROUND:

Circumsporozoite protein (CS) is the antigenic target for RTS,S, the most advanced malaria vaccine to date. Heterologous prime-boost with the viral vectors simian adenovirus 63 (ChAd63)-modified vaccinia virus Ankara (MVA) is the most potent inducer of T-cells in humans, demonstrating significant efficacy when expressing the preerythrocytic antigen insert multiple epitope-thrombospondin-related adhesion protein (ME-TRAP). We hypothesized that ChAd63-MVA containing CS may result in a significant clinical protective efficacy.

METHODS:

We conducted an open-label, 2-site, partially randomized Plasmodium falciparum sporozoite controlled human malaria infection (CHMI) study to compare the clinical efficacy of ChAd63-MVA CS with ChAd63-MVA ME-TRAP.

RESULTS:

One of 15 vaccinees (7%) receiving ChAd63-MVA CS and 2 of 15 (13%) receiving ChAd63-MVA ME-TRAP achieved sterile protection after CHMI. Three of 15 vaccinees (20%) receiving ChAd63-MVA CS and 5 of 15 (33%) receiving ChAd63-MVA ME-TRAP demonstrated a delay in time to treatment, compared with unvaccinated controls. In quantitative polymerase chain reaction analyses, ChAd63-MVA CS was estimated to reduce the liver parasite burden by 69%-79%, compared with 79%-84% for ChAd63-MVA ME-TRAP.

CONCLUSIONS:

ChAd63-MVA CS does reduce the liver parasite burden, but ChAd63-MVA ME-TRAP remains the most promising antigenic insert for a vectored liver-stage vaccine. Detailed analyses of parasite kinetics may allow detection of smaller but biologically important differences in vaccine efficacy that can influence future vaccine development.

CLINICAL TRIALS REGISTRATION:

NCT01623557.

KEYWORDS:

CHMI; CS; ChAd63; ME-TRAP; MVA; P. falciparum; malaria; vaccine

PMID:
25336730
PMCID:
PMC4354983
DOI:
10.1093/infdis/jiu579
[Indexed for MEDLINE]
Free PMC Article

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