SARS-CoV-2 specific nanobodies neutralize different variants of concern and reduce virus load in the brain of h-ACE2 transgenic mice
Since the beginning of the COVID-19 pandemic, there has been a significant need to develop antivirals and vaccines to combat the disease. In this work, we developed llama-derived nanobodies (Nbs) directed against the receptor binding domain (RBD) and other domains of the Spike (S) protein of SARS-Co...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | info:ar-repo/semantics/artículo |
| Language: | Inglés |
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MDPI
2024
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| Online Access: | http://hdl.handle.net/20.500.12123/18374 https://www.mdpi.com/1999-4915/16/2/185 https://doi.org/10.3390/v16020185 |
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| author | Pavan, Florencia Bok, Marina Betanzos San Juan, Rafael Malito, Juan Pablo Marcoppido, Gisela Ariana Franco, Diego Rafael Militelo, Daniela Ayelen Schammas, Juan Manuel Bari, Sara Elizabeth Stone, William B. López, Krisangel Porier, Danielle LaBrie Muller, John Anthony Auguste, Albert J. Yuan, Lijuan Wigdorovitz, Andres Parreño, Gladys Viviana Ibañez, Lorena Itat |
| author_browse | Auguste, Albert J. Bari, Sara Elizabeth Betanzos San Juan, Rafael Bok, Marina Franco, Diego Rafael Ibañez, Lorena Itat López, Krisangel Malito, Juan Pablo Marcoppido, Gisela Ariana Militelo, Daniela Ayelen Muller, John Anthony Parreño, Gladys Viviana Pavan, Florencia Porier, Danielle LaBrie Schammas, Juan Manuel Stone, William B. Wigdorovitz, Andres Yuan, Lijuan |
| author_facet | Pavan, Florencia Bok, Marina Betanzos San Juan, Rafael Malito, Juan Pablo Marcoppido, Gisela Ariana Franco, Diego Rafael Militelo, Daniela Ayelen Schammas, Juan Manuel Bari, Sara Elizabeth Stone, William B. López, Krisangel Porier, Danielle LaBrie Muller, John Anthony Auguste, Albert J. Yuan, Lijuan Wigdorovitz, Andres Parreño, Gladys Viviana Ibañez, Lorena Itat |
| author_sort | Pavan, Florencia |
| collection | INTA Digital |
| description | Since the beginning of the COVID-19 pandemic, there has been a significant need to develop antivirals and vaccines to combat the disease. In this work, we developed llama-derived nanobodies (Nbs) directed against the receptor binding domain (RBD) and other domains of the Spike (S) protein of SARS-CoV-2. Most of the Nbs with neutralizing properties were directed to RBD and were able to block S-2P/ACE2 interaction. Three neutralizing Nbs recognized the N-terminal domain (NTD) of the S-2P protein. Intranasal administration of Nbs induced protection ranging from 40% to 80% after challenge with the WA1/2020 strain in k18-hACE2 transgenic mice. Interestingly, protection was associated with a significant reduction in virus replication in nasal turbinates and a reduction in virus load in the brain. Employing pseudovirus neutralization assays, we identified Nbs with neutralizing capacity against the Alpha, Beta, Delta, and Omicron variants, including a Nb capable of neutralizing all variants tested. Furthermore, cocktails of different Nbs performed better than individual Nbs at neutralizing two Omicron variants (B.1.529 and BA.2). Altogether, the data suggest the potential of SARS-CoV-2 specific Nbs for intranasal treatment of COVID-19 encephalitis. |
| format | info:ar-repo/semantics/artículo |
| id | INTA18374 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2024 |
| publishDateRange | 2024 |
| publishDateSort | 2024 |
| publisher | MDPI |
| publisherStr | MDPI |
| record_format | dspace |
| spelling | INTA183742024-07-04T11:00:39Z SARS-CoV-2 specific nanobodies neutralize different variants of concern and reduce virus load in the brain of h-ACE2 transgenic mice Pavan, Florencia Bok, Marina Betanzos San Juan, Rafael Malito, Juan Pablo Marcoppido, Gisela Ariana Franco, Diego Rafael Militelo, Daniela Ayelen Schammas, Juan Manuel Bari, Sara Elizabeth Stone, William B. López, Krisangel Porier, Danielle LaBrie Muller, John Anthony Auguste, Albert J. Yuan, Lijuan Wigdorovitz, Andres Parreño, Gladys Viviana Ibañez, Lorena Itat Severe Acute Respiratory Syndrome Coronavirus 2 Antigen Antibody Reactions Transgenic Animals Mice Nanobiotechnology Coronavirus del Síndrome Respiratorio Agudo Grave 2 Reacción Antígeno Anticuerpo Animales Transgénicos Ratón Nanobiotecnología SARS-CoV-2 Intranasal Treatment Tratamiento Intranasal Since the beginning of the COVID-19 pandemic, there has been a significant need to develop antivirals and vaccines to combat the disease. In this work, we developed llama-derived nanobodies (Nbs) directed against the receptor binding domain (RBD) and other domains of the Spike (S) protein of SARS-CoV-2. Most of the Nbs with neutralizing properties were directed to RBD and were able to block S-2P/ACE2 interaction. Three neutralizing Nbs recognized the N-terminal domain (NTD) of the S-2P protein. Intranasal administration of Nbs induced protection ranging from 40% to 80% after challenge with the WA1/2020 strain in k18-hACE2 transgenic mice. Interestingly, protection was associated with a significant reduction in virus replication in nasal turbinates and a reduction in virus load in the brain. Employing pseudovirus neutralization assays, we identified Nbs with neutralizing capacity against the Alpha, Beta, Delta, and Omicron variants, including a Nb capable of neutralizing all variants tested. Furthermore, cocktails of different Nbs performed better than individual Nbs at neutralizing two Omicron variants (B.1.529 and BA.2). Altogether, the data suggest the potential of SARS-CoV-2 specific Nbs for intranasal treatment of COVID-19 encephalitis. Instituto de Virología Fil: Pavan, Florencia. Universidad de Buenos Aires. Instituto de Química Física de los Materiales, Medio Ambiente y Energía (INQUIMAE); Argentina Fil: Pavan, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Bok, Marina. Instituto Nacional de Tecnología Agropecuaria (INTA). INCUINTA. Instituto de Virología e Innovaciones Tecnologicas; Argentina Fil: Bok, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Betanzos San Juan, Rafael. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales (IQUIBICEN). Instituto de Química Biológica. Departamento de Química Biológicas; Argentina Fil: Betanzos San Juan, Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Malito, Juan Pablo. Instituto Nacional de Tecnología Agropecuaria (INTA). INCUINTA. Instituto de Virología e Innovaciones Tecnologicas; Argentina Fil: Malito, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Marcoppido, Gisela Ariana. Instituto Nacional de Tecnología Agropecuaria (INTA). Centro de Investigaciones en Ciencias Veterinarias y Agronómicas (CICVyA); Argentina Fil: Franco, Diego Rafael. Instituto Nacional de Tecnología Agropecuaria (INTA). Centro de Investigaciones en Ciencias Veterinarias y Agronómicas (CICVyA); Argentina Fil: Militelo, Daniela Ayelen. Universidad de Buenos Aires. Instituto de Química Física de los Materiales, Medio Ambiente y Energía (INQUIMAE); Argentina Fil: Militelo, Daniela Ayelen. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Schammas, Juan Manuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología e Innovaciones Tecnológicas; Argentina Fil: Schammas, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Bari, Sara Elizabeth. Universidad de Buenos Aires. Instituto de Química Física de los Materiales, Medio Ambiente y Energía (INQUIMAE); Argentina Fil: Bari, Sara Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Stone, William B. Virginia Polytechnic Institute and State University. Fralin Life Science Institute. College of Agriculture and Life Sciences. Department of Entomology; Estados Unidos Fil: López, Krisangel. Virginia Polytechnic Institute and State University. Fralin Life Science Institute. College of Agriculture and Life Sciences. Department of Entomology; Estados Unidos Fil: Porier, Danielle LaBrie. Virginia Polytechnic Institute and State University. Fralin Life Science Institute. College of Agriculture and Life Sciences. Department of Entomology; Estados Unidos Fil: Muller, John Anthony. Virginia Polytechnic Institute and State University. Fralin Life Science Institute. College of Agriculture and Life Sciences. Department of Entomology; Estados Unidos Fil: Auguste, Albert J. Virginia Polytechnic Institute and State University. Fralin Life Science Institute. College of Agriculture and Life Sciences. Department of Entomology; Estados Unidos Fil: Auguste, Albert J. Virginia Polytechnic Institute and State University. Center for Emerging, Zoonotic, and Arthropod-borne Pathogens; Estados Unidos Fil: Yuan, Lijuan. Virginia Polytechnic Institute and State University. Center for Emerging, Zoonotic, and Arthropod-borne Pathogens; Estados Unidos Fil: Yuan, Lijuan. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos Fil: Wigdorovitz, Andres. Instituto Nacional de Tecnología Agropecuaria (INTA). INCUINTA. Instituto de Virología e Innovaciones Tecnológicas (IVIT); Argentina Fil: Wigdorovitz, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). INCUINTA. Instituto de Virologia e Innovaciones Tecnologicas (IVIT); Argentina Fil: Parreño, Gladys Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Parreño, Gladys Viviana. Virginia Polytechnic Institute and State University. Virginia-Maryland College of Veterinary Medicine. Department of Biomedical Sciences and Pathobiology; Estados Unidos Fil: Ibañez, Lorena Itat. Universidad de Buenos Aires. Instituto de Química Física de los Materiales, Medio Ambiente y Energía (INQUIMAE); Argentina Fil: Ibañez, Lorena Itat. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina 2024-07-04T10:44:10Z 2024-07-04T10:44:10Z 2024-02 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/18374 https://www.mdpi.com/1999-4915/16/2/185 1999-4915 https://doi.org/10.3390/v16020185 eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf MDPI Viruses 16 (2) : 185 (Febrero 2024) |
| spellingShingle | Severe Acute Respiratory Syndrome Coronavirus 2 Antigen Antibody Reactions Transgenic Animals Mice Nanobiotechnology Coronavirus del Síndrome Respiratorio Agudo Grave 2 Reacción Antígeno Anticuerpo Animales Transgénicos Ratón Nanobiotecnología SARS-CoV-2 Intranasal Treatment Tratamiento Intranasal Pavan, Florencia Bok, Marina Betanzos San Juan, Rafael Malito, Juan Pablo Marcoppido, Gisela Ariana Franco, Diego Rafael Militelo, Daniela Ayelen Schammas, Juan Manuel Bari, Sara Elizabeth Stone, William B. López, Krisangel Porier, Danielle LaBrie Muller, John Anthony Auguste, Albert J. Yuan, Lijuan Wigdorovitz, Andres Parreño, Gladys Viviana Ibañez, Lorena Itat SARS-CoV-2 specific nanobodies neutralize different variants of concern and reduce virus load in the brain of h-ACE2 transgenic mice |
| title | SARS-CoV-2 specific nanobodies neutralize different variants of concern and reduce virus load in the brain of h-ACE2 transgenic mice |
| title_full | SARS-CoV-2 specific nanobodies neutralize different variants of concern and reduce virus load in the brain of h-ACE2 transgenic mice |
| title_fullStr | SARS-CoV-2 specific nanobodies neutralize different variants of concern and reduce virus load in the brain of h-ACE2 transgenic mice |
| title_full_unstemmed | SARS-CoV-2 specific nanobodies neutralize different variants of concern and reduce virus load in the brain of h-ACE2 transgenic mice |
| title_short | SARS-CoV-2 specific nanobodies neutralize different variants of concern and reduce virus load in the brain of h-ACE2 transgenic mice |
| title_sort | sars cov 2 specific nanobodies neutralize different variants of concern and reduce virus load in the brain of h ace2 transgenic mice |
| topic | Severe Acute Respiratory Syndrome Coronavirus 2 Antigen Antibody Reactions Transgenic Animals Mice Nanobiotechnology Coronavirus del Síndrome Respiratorio Agudo Grave 2 Reacción Antígeno Anticuerpo Animales Transgénicos Ratón Nanobiotecnología SARS-CoV-2 Intranasal Treatment Tratamiento Intranasal |
| url | http://hdl.handle.net/20.500.12123/18374 https://www.mdpi.com/1999-4915/16/2/185 https://doi.org/10.3390/v16020185 |
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