40 Years of Pfs48/45 Research as a Transmission-Blocking Vaccine Target of Plasmodium falciparum Malaria
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40 Years of Pfs48/45 Research as a Transmission-Blocking Vaccine Target of Plasmodium falciparum Malaria. / Sauerwein, Robert W.; Plieskatt, Jordan; Theisen, Michael.
In: American Journal of Tropical Medicine and Hygiene, Vol. 107, 2022, p. 22-26.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - 40 Years of Pfs48/45 Research as a Transmission-Blocking Vaccine Target of Plasmodium falciparum Malaria
AU - Sauerwein, Robert W.
AU - Plieskatt, Jordan
AU - Theisen, Michael
N1 - Publisher Copyright: Copyright © 2022 The author(s).
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.4269/ajtmh.21-1320
DO - 10.4269/ajtmh.21-1320
M3 - Journal article
C2 - 35895389
AN - SCOPUS:85139343410
VL - 107
SP - 22
EP - 26
JO - Journal. National Malaria Society
JF - Journal. National Malaria Society
SN - 0002-9637
ER -
ID: 323842075