Safety and Immunogenicity of Heterologous Prime-Boost Immunisation with Plasmodium falciparum Malaria Candidate Vaccines, ChAd63 ME-TRAP and MVA ME-TRAP, in Healthy Gambian and Kenyan Adults

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Abstract

Background

Heterologous prime boost immunization with chimpanzee adenovirus 63 (ChAd63) and Modified vaccinia Virus Ankara (MVA) vectored vaccines is a strategy recently shown to be capable of inducing strong cell mediated responses against several antigens from the malaria parasite. ChAd63-MVA expressing the Plasmodium falciparum pre-erythrocytic antigen ME-TRAP (multiple epitope string with thrombospondin-related adhesion protein) is a leading malaria vaccine candidate, capable of inducing sterile protection in malaria naïve adults following controlled human malaria infection (CHMI).

Methodology

We conducted two Phase Ib dose escalation clinical trials assessing the safety and immunogenicity of ChAd63-MVA ME-TRAP in 46 healthy malaria exposed adults in two African countries with similar malaria transmission patterns.

Results

ChAd63-MVA ME-TRAP was shown to be safe and immunogenic, inducing high-level T cell responses (median >1300 SFU/million PBMC).

Conclusions

ChAd63-MVA ME-TRAP is a safe and highly immunogenic vaccine regimen in adults with prior exposure to malaria. Further clinical trials to assess safety and immunogenicity in children and infants and protective efficacy in the field are now warranted.

Trial Registration

Pactr.org PACTR2010020001771828 http://www.pactr.org/

Pactr.org PACTR201008000221638 http://www.pactr.org/

ClinicalTrials.gov NCT01373879 NCT01373879

ClinicalTrials.gov NCT01379430 NCT01379430

Related collections

Author and article information

Contributors

Aric Gregson: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2013

Publication date (Electronic): 19 March 2013

Volume: 8

Issue: 3

Electronic Location Identifier: e57726

Affiliations

[1 ]Kenya Medical Research Institute, Centre for Geographical Medical Research (Coast), Kilifi, Kenya

[2 ]Medical Research Council Unit, Fajara, The Gambia

[3 ]Centre for Clinical Vaccinology and Tropical Medicine, The Jenner Institute, Churchill Hospital, Oxford, United Kingdom

[4 ]The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Oxford, United Kingdom

[5 ]Clinical Biomanufacturing Facility, University of Oxford, Churchill Hospital, Oxford, United Kingdom

[6 ]Okairòs AG, Rome, Italy

[7 ]CEINGE, Naples, Italy

[8 ]European Vaccine Initiative, Heidelberg, Germany

[9 ]Department of Molecular Medicine and Medical Biotechnology, University Federico II Naples, Naples, Italy

[10 ]Liverpool School of Tropical Medicine, Liverpool, United Kingdom

University of California Los Angeles, United States of America

Author notes

* E-mail: Susanne.sheehy@ 123456ndm.ox.ac.uk

Competing Interests: AH is a named inventor on the following patent applications on malaria vectored vaccines and immunization regimes (WO2008/122769, Adenoviral vector encoding malaria antigen; and WO 2008/122811 Novel adenovirus vectors). Authors from Okairòs are employees of and/or shareholders in Okairòs, which is developing vectored vaccines for malaria and other diseases. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Project management: PS JM NV RR KG AL EI. Conceived and designed the experiments: CO MGK SS CD JM EI PB KF KE R. Chilengi AH KB. Performed the experiments: CO MGK DK YJ CB KC AS JO EK. Analyzed the data: CO MGK DK YJ SS CB KC NA AS PB BU KF KE KB EK. Contributed reagents/materials/analysis tools: EB SM SG SC R. Cortese AN. Wrote the paper: CO MGK SS AH.

Article

Publisher ID: PONE-D-12-29316

DOI: 10.1371/journal.pone.0057726

PMC ID: 3602521

PubMed ID: 23526949

SO-VID: 0f8cc039-04a1-4e1e-a48e-674c7f12edf1

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 3 September 2012

Date accepted : 24 January 2013

Page count

Pages: 11

Funding

This work was performed by the Malaria Vectored Vaccines Consortium (MVVC), a four year integrated project funded by the European and Developing Countries Clinical Trials Partnership (EDCTP). The work was also supported by the UK National Institute of Health Research through the Oxford Biomedical Research Centre ( http://www.oxfordbrc.org/) [A91301 Adult Vaccine], the Wellcome Trust ( http://www.wellcome.ac.uk/) [084113/Z/07/Z] and the Medical Research Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.