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Genetic Diversity of the Malaria Vaccine Candidate Plasmodium falciparum Merozoite Surface Protein-3 in a Hypoendemic Transmission Environment

The N-terminal domain of Plasmodium falciparum merozoite surface protein-3 (PfMSP3) has been excluded from malaria vaccine development largely because of genetic diversity concerns. However, no study to date has followed N-terminal diversity over time. This study describes PfMSP3 variation in a hypoendemic longitudinal cohort in the Peruvian Amazon over the 2003–2006 transmission seasons. Polymerase chain reaction was used to amplify the N-terminal domain in 630 distinct P. falciparum infections, which were allele-typed by size and also screened for sequence variation using a new high-throughput technique, denaturing high performance liquid chromatography. PfMSP3 allele frequencies fluctuated significantly over the 4-year period, but sequence variation was very limited, with only 10 mutations being identified of 630 infections screened. The sequence of the PfMSP3 N-terminal domain is relatively stable over time in this setting, and further studies of its status as a vaccine candidate are therefore warranted.

Received September 29, 2008. Accepted for publication November 19, 2008.

Acknowledgments: The authors thank Dr. Michael Crowley for technical expertise and assistance in using dHPLC to screen for PfMSP3 sequence variation; Gino Nivarro Anderson, Jean Hernandez, and Patrick Sutton for help with sample processing and obtaining the corresponding epidemiologic data; and the residents of the Zungarococha community for their willingness to participate in the MIGIA study.

Financial support: This work was supported by National Institute of Health Grant R21 AI072421 and the UAB Sparkman Center for Global Health.

^* Address correspondence to Julian C. Rayner, Malaria Programme, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA. E-mail: jr9{at}sanger.ac.uk

Authors’ addresses: Stephen J. Jordan, Department of Cell Biology, University of Alabama at Birmingham, 845 19th Street South, BBRB 568, Birmingham, AL 35294-2170, Tel: 205-934-6113, Fax: 205-934-5600, E-mail: sjjordan{at}uab.edu. OraLee H. Branch, William C. Gorgas Center for Geographic Medicine, Department of Medicine, University of Alabama at Birmingham, 845 19th Street South, BBRB 556, Birmingham, AL 35294-2170, Tel: 205-934-4721, Fax: 205-934-5600, E-mail: obranch{at}uab.edu. Jean Carlos Castro, Laboratorio de Investigaciones de Productos Naturales y Antiparasitarios, Universidad Nacional de la Amazonia Peruana, Iquitos, Peru, Tel: 011-5-19-6-568-5816, Fax: 205-934-5600, E-mail: juanccgomez{at}yahoo.es. Robert A. Oster, Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, 1530 3rd Avenue South, MT 650, Birmingham, AL 35294-4410, Tel: 205-934-3376, Fax: 205-934-4262, E-mail: oster{at}uab.edu. Julian C. Rayner, William C. Gorgas Center for Geographic Medicine, Department of Medicine, University of Alabama at Birmingham, 845 19th Street South, BBRB 566, Birmingham, AL 35294-2170, Tel: 205-934-5804, Fax: 205-934-5600, E-mail: jrayner{at}uab.edu. Current address: Malaria Programme, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK, Tel: 44-1223-492327; Fax: 44-1224-494919; E-mail: jr9{at}sanger.ac.uk.

Reprint requests: Julian C. Rayner, Malaria Programme, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK, E-mail: jr9{at}sanger.ac.uk.