A human antibody epitope map of the malaria vaccine antigen Pfs25
Abstract Pfs25 is a leading antigen for a malaria transmission-blocking vaccine and shows moderate transmission-blocking activity and induction of rapidly decreasing antibody titers in clinical trials. A comprehensive definition of all transmission-reducing epitopes of Pfs25 will inform structure-gu...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-08-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-023-00712-z |
| _version_ | 1827724749198852096 |
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| author | Niharika Shukla Wai Kwan Tang Camila H. Coelho Carole A. Long Sara A. Healy Issaka Sagara Kazutoyo Miura Patrick E. Duffy Niraj H. Tolia |
| author_facet | Niharika Shukla Wai Kwan Tang Camila H. Coelho Carole A. Long Sara A. Healy Issaka Sagara Kazutoyo Miura Patrick E. Duffy Niraj H. Tolia |
| author_sort | Niharika Shukla |
| collection | DOAJ |
| description | Abstract Pfs25 is a leading antigen for a malaria transmission-blocking vaccine and shows moderate transmission-blocking activity and induction of rapidly decreasing antibody titers in clinical trials. A comprehensive definition of all transmission-reducing epitopes of Pfs25 will inform structure-guided design to enhance Pfs25-based vaccines, leading to potent transmission-blocking activity. Here, we compiled a detailed human antibody epitope map comprising epitope binning data and structures of multiple human monoclonal antibodies, including three new crystal structures of Pfs25 in complex with transmission-reducing antibodies from Malian volunteers immunized with Pfs25 conjugated to EPA and adjuvanted with AS01. These structures revealed additional epitopes in Pfs25 capable of reducing transmission and expanded this characterization to malaria-exposed humans. This work informs immunogen design to focus the antibody response to transmission-reducing epitopes of Pfs25, enabling development of more potent transmission-blocking vaccines for malaria. |
| first_indexed | 2024-03-10T22:20:05Z |
| format | Article |
| id | doaj.art-2b2a9cc4c3a14a22b8a2355e8bb81d9f |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-10T22:20:05Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-2b2a9cc4c3a14a22b8a2355e8bb81d9f2023-11-19T12:17:49ZengNature Portfolionpj Vaccines2059-01052023-08-01811910.1038/s41541-023-00712-zA human antibody epitope map of the malaria vaccine antigen Pfs25Niharika Shukla0Wai Kwan Tang1Camila H. Coelho2Carole A. Long3Sara A. Healy4Issaka Sagara5Kazutoyo Miura6Patrick E. Duffy7Niraj H. Tolia8Host-Pathogen Interactions and Structural Vaccinology Section, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthHost-Pathogen Interactions and Structural Vaccinology Section, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthPathogenesis and Immunity Section, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Development Unit, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthMalaria Research and Training Center, University of Sciences, Techniques, and TechnologyLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthPathogenesis and Immunity Section, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthHost-Pathogen Interactions and Structural Vaccinology Section, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthAbstract Pfs25 is a leading antigen for a malaria transmission-blocking vaccine and shows moderate transmission-blocking activity and induction of rapidly decreasing antibody titers in clinical trials. A comprehensive definition of all transmission-reducing epitopes of Pfs25 will inform structure-guided design to enhance Pfs25-based vaccines, leading to potent transmission-blocking activity. Here, we compiled a detailed human antibody epitope map comprising epitope binning data and structures of multiple human monoclonal antibodies, including three new crystal structures of Pfs25 in complex with transmission-reducing antibodies from Malian volunteers immunized with Pfs25 conjugated to EPA and adjuvanted with AS01. These structures revealed additional epitopes in Pfs25 capable of reducing transmission and expanded this characterization to malaria-exposed humans. This work informs immunogen design to focus the antibody response to transmission-reducing epitopes of Pfs25, enabling development of more potent transmission-blocking vaccines for malaria.https://doi.org/10.1038/s41541-023-00712-z |
| spellingShingle | Niharika Shukla Wai Kwan Tang Camila H. Coelho Carole A. Long Sara A. Healy Issaka Sagara Kazutoyo Miura Patrick E. Duffy Niraj H. Tolia A human antibody epitope map of the malaria vaccine antigen Pfs25 npj Vaccines |
| title | A human antibody epitope map of the malaria vaccine antigen Pfs25 |
| title_full | A human antibody epitope map of the malaria vaccine antigen Pfs25 |
| title_fullStr | A human antibody epitope map of the malaria vaccine antigen Pfs25 |
| title_full_unstemmed | A human antibody epitope map of the malaria vaccine antigen Pfs25 |
| title_short | A human antibody epitope map of the malaria vaccine antigen Pfs25 |
| title_sort | human antibody epitope map of the malaria vaccine antigen pfs25 |
| url | https://doi.org/10.1038/s41541-023-00712-z |
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