Schistosoma mansoni vaccine candidates identified by unbiased phage display screening in self-cured rhesus macaques
Abstract Schistosomiasis, a challenging neglected tropical disease, affects millions of people worldwide. Developing a prophylactic vaccine against Schistosoma mansoni has been hindered by the parasite’s biological complexity. In this study, we utilized the innovative phage-display immunoprecipitati...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-01-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-023-00803-x |
| _version_ | 1797363647557664768 |
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| author | Daisy Woellner-Santos Ana C. Tahira João V. M. Malvezzi Vinicius Mesel David A. Morales-Vicente Monalisa M. Trentini Lázaro M. Marques-Neto Isaac A. Matos Alex I. Kanno Adriana S. A. Pereira André A. R. Teixeira Ricardo J. Giordano Luciana C. C. Leite Carlos A. B. Pereira Ricardo DeMarco Murilo S. Amaral Sergio Verjovski-Almeida |
| author_facet | Daisy Woellner-Santos Ana C. Tahira João V. M. Malvezzi Vinicius Mesel David A. Morales-Vicente Monalisa M. Trentini Lázaro M. Marques-Neto Isaac A. Matos Alex I. Kanno Adriana S. A. Pereira André A. R. Teixeira Ricardo J. Giordano Luciana C. C. Leite Carlos A. B. Pereira Ricardo DeMarco Murilo S. Amaral Sergio Verjovski-Almeida |
| author_sort | Daisy Woellner-Santos |
| collection | DOAJ |
| description | Abstract Schistosomiasis, a challenging neglected tropical disease, affects millions of people worldwide. Developing a prophylactic vaccine against Schistosoma mansoni has been hindered by the parasite’s biological complexity. In this study, we utilized the innovative phage-display immunoprecipitation followed by a sequencing approach (PhIP-Seq) to screen the immune response of 10 infected rhesus macaques during self-cure and challenge-resistant phases, identifying vaccine candidates. Our high-throughput S. mansoni synthetic DNA phage-display library encoded 99.6% of 119,747 58-mer peptides, providing comprehensive coverage of the parasite’s proteome. Library screening with rhesus macaques’ antibodies, from the early phase of establishment of parasite infection, identified significantly enriched epitopes of parasite extracellular proteins known to be expressed in the digestive tract, shifting towards intracellular proteins during the late phase of parasite clearance. Immunization of mice with a selected pool of PhIP-Seq-enriched phage-displayed peptides from MEG proteins, cathepsins B, and asparaginyl endopeptidase significantly reduced worm burden in a vaccination assay. These findings enhance our understanding of parasite-host immune responses and provide promising prospects for developing an effective schistosomiasis vaccine. |
| first_indexed | 2024-03-08T16:24:05Z |
| format | Article |
| id | doaj.art-3538479b2fca4d06b0fefa7e31cf9fdf |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-08T16:24:05Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-3538479b2fca4d06b0fefa7e31cf9fdf2024-01-07T12:09:43ZengNature Portfolionpj Vaccines2059-01052024-01-019111910.1038/s41541-023-00803-xSchistosoma mansoni vaccine candidates identified by unbiased phage display screening in self-cured rhesus macaquesDaisy Woellner-Santos0Ana C. Tahira1João V. M. Malvezzi2Vinicius Mesel3David A. Morales-Vicente4Monalisa M. Trentini5Lázaro M. Marques-Neto6Isaac A. Matos7Alex I. Kanno8Adriana S. A. Pereira9André A. R. Teixeira10Ricardo J. Giordano11Luciana C. C. Leite12Carlos A. B. Pereira13Ricardo DeMarco14Murilo S. Amaral15Sergio Verjovski-Almeida16Laboratório de Ciclo Celular, Instituto ButantanLaboratório de Ciclo Celular, Instituto ButantanLaboratório de Ciclo Celular, Instituto ButantanLaboratório de Ciclo Celular, Instituto ButantanLaboratório de Ciclo Celular, Instituto ButantanLaboratório de Desenvolvimento de Vacinas, Instituto ButantanLaboratório de Desenvolvimento de Vacinas, Instituto ButantanInstituto de Química, Universidade de São PauloLaboratório de Desenvolvimento de Vacinas, Instituto ButantanLaboratório de Ciclo Celular, Instituto ButantanInstituto de Química, Universidade de São PauloInstituto de Química, Universidade de São PauloLaboratório de Desenvolvimento de Vacinas, Instituto ButantanInstituto de Matemática e Estatística, Universidade de São PauloInstituto de Física de São Carlos, Universidade de São PauloLaboratório de Ciclo Celular, Instituto ButantanLaboratório de Ciclo Celular, Instituto ButantanAbstract Schistosomiasis, a challenging neglected tropical disease, affects millions of people worldwide. Developing a prophylactic vaccine against Schistosoma mansoni has been hindered by the parasite’s biological complexity. In this study, we utilized the innovative phage-display immunoprecipitation followed by a sequencing approach (PhIP-Seq) to screen the immune response of 10 infected rhesus macaques during self-cure and challenge-resistant phases, identifying vaccine candidates. Our high-throughput S. mansoni synthetic DNA phage-display library encoded 99.6% of 119,747 58-mer peptides, providing comprehensive coverage of the parasite’s proteome. Library screening with rhesus macaques’ antibodies, from the early phase of establishment of parasite infection, identified significantly enriched epitopes of parasite extracellular proteins known to be expressed in the digestive tract, shifting towards intracellular proteins during the late phase of parasite clearance. Immunization of mice with a selected pool of PhIP-Seq-enriched phage-displayed peptides from MEG proteins, cathepsins B, and asparaginyl endopeptidase significantly reduced worm burden in a vaccination assay. These findings enhance our understanding of parasite-host immune responses and provide promising prospects for developing an effective schistosomiasis vaccine.https://doi.org/10.1038/s41541-023-00803-x |
| spellingShingle | Daisy Woellner-Santos Ana C. Tahira João V. M. Malvezzi Vinicius Mesel David A. Morales-Vicente Monalisa M. Trentini Lázaro M. Marques-Neto Isaac A. Matos Alex I. Kanno Adriana S. A. Pereira André A. R. Teixeira Ricardo J. Giordano Luciana C. C. Leite Carlos A. B. Pereira Ricardo DeMarco Murilo S. Amaral Sergio Verjovski-Almeida Schistosoma mansoni vaccine candidates identified by unbiased phage display screening in self-cured rhesus macaques npj Vaccines |
| title | Schistosoma mansoni vaccine candidates identified by unbiased phage display screening in self-cured rhesus macaques |
| title_full | Schistosoma mansoni vaccine candidates identified by unbiased phage display screening in self-cured rhesus macaques |
| title_fullStr | Schistosoma mansoni vaccine candidates identified by unbiased phage display screening in self-cured rhesus macaques |
| title_full_unstemmed | Schistosoma mansoni vaccine candidates identified by unbiased phage display screening in self-cured rhesus macaques |
| title_short | Schistosoma mansoni vaccine candidates identified by unbiased phage display screening in self-cured rhesus macaques |
| title_sort | schistosoma mansoni vaccine candidates identified by unbiased phage display screening in self cured rhesus macaques |
| url | https://doi.org/10.1038/s41541-023-00803-x |
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