Pfs47 as a Malaria Transmission-Blocking Vaccine Target

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  • 1 Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland

Transmission-blocking vaccines (TBVs), pioneered by Richard Carter and others, aim to prevent parasite development in the mosquito vector and are a promising new tool for malaria elimination. Pfs47, recently identified as a TBV target, is a three-domain 6-cysteine protein on the surface of Plasmodium falciparum sexual stages. Pfs47 allows the parasite to evade mosquito immunity and is key for P. falciparum infection of the dominant malaria vectors Anopheles gambiae, Anopheles dirus, and Anopheles albimanus. Antibodies against Pfs47 domain 2 (D2) have significant transmission-blocking activity that prevents Plasmodium ookinete development and is independent of human complement. Strong transmission-blocking activity has been mapped to a region of 52 amino acids in Pfs47 D2. Efforts to optimize the immunogenicity of the Pfs47 D2 antigen with a viral-like particle have been successful, and the efficacy of a P47-based TBV was confirmed in vivo with Pbs47, the orthologue of Pfs47 in the mouse malaria parasite Plasmodium berghei. The current evidence warrants further development and clinical testing of a Pfs47-based TBV.

Author Notes

Address correspondence to Alvaro Molina-Cruz or Carolina Barillas-Mury, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Pkwy., Rockville, MD 20852. E-mails: amolina-cruz@niaid.nih.gov or cbarillas@niaid.nih.gov

Financial support: This work was supported by the Intramural Research Program of the Division of Intramural Research (NIAID/NIH Z01AI000947).

Authors’ addresses: Alvaro Molina-Cruz and Carolina Barillas-Mury, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, E-mails: amolina-cruz@niaid.nih.gov and cbarillas@niaid.nih.gov.

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