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Infection and Immunity, May 2006, p. 2706-2716, Vol. 74, No. 5
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.5.2706-2716.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Safety, Immunogenicity, and Efficacy of Prime-Boost Immunization with Recombinant Poxvirus FP9 and Modified Vaccinia Virus Ankara Encoding the Full-Length Plasmodium falciparum Circumsporozoite Protein

Michael Walther,1* Fiona M. Thompson,1 Susanna Dunachie,1 Sheila Keating,1 Stephen Todryk,1 Tamara Berthoud,1 Laura Andrews,2 Rikke F. Andersen,2 Anne Moore,2 Sarah C. Gilbert,2 Ian Poulton,1 Filip Dubovsky,3 Eveline Tierney,3 Simon Correa,1 Angela Huntcooke,1 Geoffrey Butcher,4 Jack Williams,5 Robert E. Sinden,4 and Adrian V. S. Hill1,2

Centre for Clinical Vaccinology & Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Churchill Hospital, Oxford OX3 7LJ, United Kingdom,1 The Wellcome Trust Centre for Human Genetics, Nuffield Department of Clinical Medicine, Oxford University, Roosevelt Drive, Oxford OX3 7BN, United Kingdom,2 PATH Malaria Vaccine Initiative, Bethesda, Maryland 20814,3 Department of Biological Sciences, Sir Alexander Fleming Building, Imperial College London, Imperial College Road, London SW7 2AZ, United Kingdom,4 Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, Maryland 209105

Received 15 December 2005/ Returned for modification 3 February 2006/ Accepted 25 February 2006

Heterologous prime-boost immunization with DNA and various recombinant poxviruses encoding malaria antigens is capable of inducing strong cell-mediated immune responses and partial protection in human sporozoite challenges. Here we report a series of trials assessing recombinant fowlpox virus and modified vaccinia virus Ankara encoding the Plasmodium falciparum circumsporozoite protein in various prime-boost combinations, doses, and application routes. For the first time, these vaccines were administered intramuscularly and at doses of up to 5 x 108 PFU. Vaccines containing this antigen proved safe and induced modest immune responses but showed no evidence of efficacy in a sporozoite challenge.


* Corresponding author. Present address: MRC Laboratories, Fajara P.O. Box 273, Banjul, The Gambia. Phone: 00220 4497928. Fax: 00220 4494485. E-mail: mwalther{at}mrc.gm.

Editor: W. A. Petri, Jr.


Infection and Immunity, May 2006, p. 2706-2716, Vol. 74, No. 5
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.5.2706-2716.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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