Structure of the malaria vaccine candidate Pfs48/45 and its recognition by transmission blocking antibodies
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Abstract
An effective malaria vaccine remains a global health priority and vaccine immunogens which prevent transmission of the parasite will have important roles in multi-component vaccines. One of the most promising candidates for inclusion in a transmission-blocking malaria vaccine is the gamete surface protein Pfs48/45, which is essential for development of the parasite in the mosquito midgut. Indeed, antibodies which bind Pfs48/45 can prevent transmission if ingested with the parasite as part of the mosquito bloodmeal. Here we present the structure of full-length Pfs48/45, showing its three domains to form a dynamic, planar, triangular arrangement. We reveal where transmission-blocking and non-blocking antibodies bind on Pfs48/45. Finally, we demonstrate that antibodies which bind across this molecule can be transmission-blocking. These studies will guide the development of future Pfs48/45-based vaccine immunogens.
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Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Comparative protein structure modeling using MODELLER
Webb, B., & Sali, A. (2016) · Current Protocols in Protein Science · doi:10.1002/cpps.20 · Cited by 730 · see citing works
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- Authors
- Ko, K.-T., Lennartz, F., Mekhaiel, D., Guloglu, B., Marini, A., Deuker, D. J., Long, C. A., Jore, M. M., Miura, K., Biswas, S., & Higgins, M. K.
- Affiliations
- University of Oxford (GB)
- National Institutes of Health (US)
- Radboud University Medical Center (NL)
- Corresponding author
- Biswas, Sumi
- Higgins, Matthew K.
- ORCID
- Venue
- Nature Communications
- Published
- 2022-09-24
- Volume
- 13
- Issue
- 1
- Pages
- 5603-5603
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC9509318
- OpenAlex
- W4297183458
- Cited by
- 32
- References
- 3
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 7 · 2023: 5 · 2022: 2
- FWCI
- 5.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- RCUK | Medical Research Council (MR/R001138/1)
- Wellcome Trust (220797/Z/20/Z)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- Pfs48/45, malaria vaccine, transmission-blocking antibodies, protein structure, Plasmodium falciparum, mosquito midgut, vaccine immunogens, antibody binding sites
- MeSH terms
- Animals, Antibodies, Protozoan, Membrane Proteins, Plasmodium falciparum, Protozoan Proteins, Malaria, Falciparum, Malaria Vaccines, Antibodies, Blocking
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