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Blood-stage Challenge for Malaria Vaccine Efficacy Trials: A Pilot Study with Discussion of Safety and Potential Value

There is increasing interest in malaria vaccines targeting the asexual blood stage of Plasmodium falciparum. Without accepted immunologic correlates of clinical protection, challenge studies are useful for assessing the efficacy of candidate vaccines in vivo in healthy volunteers. We report a pilot study of a safe and robust challenge protocol using a blood-stage inoculum. We have applied well-validated trial endpoints and twice daily real-time quantitative polymerase chain reaction monitoring of parasitemia to blood-stage challenge, which enabled direct comparison with sporozoite challenge. We found that greater accuracy in quantification of blood-stage growth rates can be achieved with blood-stage challenge. This finding may provide greater power to detect partial efficacy of many blood-stage candidate vaccines. We discuss the potential utility of blood-stage challenge studies in accelerating malaria vaccine development.

Received December 3, 2007. Accepted for publication January 17, 2008.

Acknowledgments: We thank Ian Poulton and Michael Walther for assistance with the trial, Nicola Alder for statistical calculations, Gregor Lawrence for supplying the inoculum, and Qin Cheng for generous help with protocols and access to previous data.

Financial support: This study was supported by the Medical Research Council (United Kingdom) and the Wellcome Trust.

^* Address correspondence to Alexander D. Douglas, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, OX3 7LJ, United Kingdom. E-mail: sandyddouglas{at}gmail.com

Authors’ addresses: Frances Sanderson, Alexander D. Douglas, Angela Hunt-Cooke, and Philip Bejon, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, University of Oxford, Oxford, OX3 7LJ, United Kingdom, Telephone: 44-1865-857401, Fax: 44-1865-857471. Laura Andrews and Adrian V. S. Hill, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, United Kingdom, Telephone: 44-1865-287500, Fax: 44-1865-287686.

Reprint requests: Adrian V. S. Hill, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom.