The Virtues and Vices of Pfs230: From Vaccine Concept to Vaccine Candidate

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  • 1 Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

Among the Plasmodium falciparum surface antigens reported by Richard Carter and his colleagues decades ago, Pfs230 is currently the target of the most advanced candidate for a malaria transmission-blocking vaccine. First identified by its orthologue in the avian malaria parasite Plasmodium gallinaceum, the large cysteine-rich 14-domain Pfs230 antigen is displayed on the surface of gametes that emerge in the mosquito midgut. Gametes lacking Pfs230 cannot bind to red blood cells nor develop further into oocysts. Human antibodies against Pfs230 lyse gametes in the presence of complement, which largely explains serum transmission-blocking activity in Pfs230 antisera. A protein–protein conjugate vaccine that incorporates the first domain of the Pfs230 antigen induced greater serum transmission-reducing activity versus a similarly manufactured Pfs25 vaccine in U.S. trials, and is currently in phase II field trials in Mali.

Author Notes

Address correspondence to Patrick E. Duffy, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 29 Lincoln Dr., Bldg. 29B, Bethesda, MD 20892. E-mail: patrick.duffy@nih.gov

Financial support: P. E. D. is supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH.

Disclaimer: The funder had no role in preparation of the manuscript or the decision to publish.

Disclosures: P. E. D. is an inventor on malaria vaccine patents but receives no financial compensation from any patents. He is an employee of the U.S. government and has no financial interest in any for-profit vaccine entity.

Author’s address: Patrick E. Duffy, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, E-mail: patrick.duffy@nih.gov.

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