40 Years of Pfs48/45 Research as a Transmission-Blocking Vaccine Target of Plasmodium falciparum Malaria

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  • 1 TropIQ Health Sciences, Nijmegen, The Netherlands;
  • | 2 Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark;
  • | 3 Centre for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark

In the early 1980s, Richard Carter was among the first researchers to identify the sexual stage-specific Pfs48/45 protein, leading to the identification of target epitopes. Carter predicted its tertiary conformation while involved in a number of studies on naturally acquired sexual stage-specific antibodies. Pfs48/45 is a cysteine-rich surface protein of sexual stages of Plasmodium falciparum that plays a critical role in male gamete fertility. Antibodies against Pfs48/45 prevent parasite development in the mosquito vector, and therefore prevent the spread of malaria in the population. Since the gene was sequenced in the early 1990s, Pfs48/45 has been considered a prime target candidate for a malaria transmission-blocking vaccine. However, major manufacturing challenges—in particular, difficulty realizing satisfactory yields of a properly folded protein for the induction of functional antibodies—delayed clinical development significantly. These challenges were met roughly 20 years later. The first clinical trial with a Pfs48/45 subunit vaccine (R0.6C) was started in the Netherlands in early 2021. The excellent contributions to the long and winding path of Pfs48/45 research by Richard Carter are well recognized and are an integrated part of his seminal contributions to unraveling Plasmodium sexual stage biology.

Author Notes

Address correspondence to Robert Sauerwein, TropIQ Health Sciences, Transistorweg 5, Nijmegen, The Netherlands, 6534 AT. E-mail: r.sauerwein@tropiq.nl

Financial support: M. T. H. and J. L. P. were supported under a grant from the European and Developing Countries Clinical Trials Partnership (RIA2018SV-2311) for the continued development of R0.6C and ProC6C.

Authors’ addresses: Robert W. Sauerwein, TropIQ Health Sciences, Nijmegen, The Netherlands, E-mail: r.sauerwein@tropiq.nl. Jordan Plieskatt, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark, E-mail: jplieskatt@gmail.com. Michael Theisen, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark, and Centre for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark, E-mail: mth@ssi.dk.

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