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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

2006; American Society for Microbiology; Volume: 74; Issue: 5 Linguagem: Inglês

10.1128/iai.74.5.2706-2716.2006

1098-5522

Michael Walther, Fiona M. Thompson, Susanna Dunachie, Sheila M. Keating, Stephen Todryk, Tamara Berthoud, Laura Andrews, Rikke Fredslund Andersen, Anne Moore, Sarah C. Gilbert, Ian Poulton, Filip Dubovsky, E L Tierney, Simon Correa, Angela Hunt‐Cooke, Geoffrey A. Butcher, Jack Williams, Robert E. Sinden, Adrian V. S. Hill,

Virus-based gene therapy research

ABSTRACT 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 × 10 8 PFU. Vaccines containing this antigen proved safe and induced modest immune responses but showed no evidence of efficacy in a sporozoite challenge.