A potent and durable malaria transmission-blocking vaccine designed from a single-component 60-copy Pfs230D1 nanoparticle
Abstract Malaria transmission-blocking vaccines (TBVs) reduce disease transmission by breaking the continuous cycle of infection between the human host and the mosquito vector. Domain 1 (D1) of Pfs230 is a leading TBV candidate and comprises the majority of transmission-reducing activity (TRA) elici...
| 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/s41541-023-00709-8 |
| _version_ | 1797578308380000256 |
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| author | Nichole D. Salinas Rui Ma Thayne H. Dickey Holly McAleese Tarik Ouahes Carole A. Long Kazutoyo Miura Lynn E. Lambert Niraj H. Tolia |
| author_facet | Nichole D. Salinas Rui Ma Thayne H. Dickey Holly McAleese Tarik Ouahes Carole A. Long Kazutoyo Miura Lynn E. Lambert Niraj H. Tolia |
| author_sort | Nichole D. Salinas |
| collection | DOAJ |
| description | Abstract Malaria transmission-blocking vaccines (TBVs) reduce disease transmission by breaking the continuous cycle of infection between the human host and the mosquito vector. Domain 1 (D1) of Pfs230 is a leading TBV candidate and comprises the majority of transmission-reducing activity (TRA) elicited by Pfs230. Here we show that the fusion of Pfs230D1 to a 60-copy multimer of the catalytic domain of dihydrolipoyl acetyltransferase protein (E2p) results in a single-component nanoparticle composed of 60 copies of the fusion protein with high stability, homogeneity, and production yields. The nanoparticle presents a potent human transmission-blocking epitope within Pfs230D1, indicating the antigen is correctly oriented on the surface of the nanoparticle. Two vaccinations of New Zealand White rabbits with the Pfs230D1 nanoparticle elicited a potent and durable antibody response with high TRA when formulated in two distinct adjuvants suitable for translation to human use. This single-component nanoparticle vaccine may play a key role in malaria control and has the potential to improve production pipelines and the cost of manufacturing of a potent and durable TBV. |
| first_indexed | 2024-03-10T22:20:04Z |
| format | Article |
| id | doaj.art-2ab6d2c8491e429d86c474230614ad0e |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-10T22:20:04Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-2ab6d2c8491e429d86c474230614ad0e2023-11-19T12:17:45ZengNature Portfolionpj Vaccines2059-01052023-08-018111110.1038/s41541-023-00709-8A potent and durable malaria transmission-blocking vaccine designed from a single-component 60-copy Pfs230D1 nanoparticleNichole D. Salinas0Rui Ma1Thayne H. Dickey2Holly McAleese3Tarik Ouahes4Carole A. Long5Kazutoyo Miura6Lynn E. Lambert7Niraj 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 HealthHost-Pathogen Interactions and Structural Vaccinology Section, Laboratory of Malaria Immunology and Vaccinology, 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 HealthVaccine Development Unit, 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 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 HealthHost-Pathogen Interactions and Structural Vaccinology Section, Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthAbstract Malaria transmission-blocking vaccines (TBVs) reduce disease transmission by breaking the continuous cycle of infection between the human host and the mosquito vector. Domain 1 (D1) of Pfs230 is a leading TBV candidate and comprises the majority of transmission-reducing activity (TRA) elicited by Pfs230. Here we show that the fusion of Pfs230D1 to a 60-copy multimer of the catalytic domain of dihydrolipoyl acetyltransferase protein (E2p) results in a single-component nanoparticle composed of 60 copies of the fusion protein with high stability, homogeneity, and production yields. The nanoparticle presents a potent human transmission-blocking epitope within Pfs230D1, indicating the antigen is correctly oriented on the surface of the nanoparticle. Two vaccinations of New Zealand White rabbits with the Pfs230D1 nanoparticle elicited a potent and durable antibody response with high TRA when formulated in two distinct adjuvants suitable for translation to human use. This single-component nanoparticle vaccine may play a key role in malaria control and has the potential to improve production pipelines and the cost of manufacturing of a potent and durable TBV.https://doi.org/10.1038/s41541-023-00709-8 |
| spellingShingle | Nichole D. Salinas Rui Ma Thayne H. Dickey Holly McAleese Tarik Ouahes Carole A. Long Kazutoyo Miura Lynn E. Lambert Niraj H. Tolia A potent and durable malaria transmission-blocking vaccine designed from a single-component 60-copy Pfs230D1 nanoparticle npj Vaccines |
| title | A potent and durable malaria transmission-blocking vaccine designed from a single-component 60-copy Pfs230D1 nanoparticle |
| title_full | A potent and durable malaria transmission-blocking vaccine designed from a single-component 60-copy Pfs230D1 nanoparticle |
| title_fullStr | A potent and durable malaria transmission-blocking vaccine designed from a single-component 60-copy Pfs230D1 nanoparticle |
| title_full_unstemmed | A potent and durable malaria transmission-blocking vaccine designed from a single-component 60-copy Pfs230D1 nanoparticle |
| title_short | A potent and durable malaria transmission-blocking vaccine designed from a single-component 60-copy Pfs230D1 nanoparticle |
| title_sort | potent and durable malaria transmission blocking vaccine designed from a single component 60 copy pfs230d1 nanoparticle |
| url | https://doi.org/10.1038/s41541-023-00709-8 |
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