RSV A2-Based Prefusion F Vaccine Candidates Induce RSV A and RSV B Cross Binding and Neutralizing Antibodies and Provide Protection against RSV A and RSV B Challenge in Preclinical Models
RSV is divided into two antigenic subtypes, RSV A and RSV B, which is largely based on the variation in the G protein, while the fusion protein F is more conserved and a target for antibody-mediated neutralization. Here we evaluate the breadth of the protective immune responses across RSV A and RSV...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/11/3/672 |
| _version_ | 1797608694665445376 |
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| author | Freek Cox Eirikur Saeland Anne Thoma Ward van den Hoogen Lisanne Tettero Joke Drijver Cornelis Vaneman Yolinda van Polanen Tina Ritschel Arangassery Rosemary Bastian Benoit Callendret Roland Zahn Leslie van der Fits |
| author_facet | Freek Cox Eirikur Saeland Anne Thoma Ward van den Hoogen Lisanne Tettero Joke Drijver Cornelis Vaneman Yolinda van Polanen Tina Ritschel Arangassery Rosemary Bastian Benoit Callendret Roland Zahn Leslie van der Fits |
| author_sort | Freek Cox |
| collection | DOAJ |
| description | RSV is divided into two antigenic subtypes, RSV A and RSV B, which is largely based on the variation in the G protein, while the fusion protein F is more conserved and a target for antibody-mediated neutralization. Here we evaluate the breadth of the protective immune responses across RSV A and RSV B subtypes, induced by vaccines based on the RSV A-based fusion protein, stabilized in the prefusion conformation (preF) in preclinical models. Immunization of naïve cotton rats with preF subunit or preF encoded by a replication incompetent Adenoviral 26, induced antibodies capable of neutralizing recent RSV A and RSV B clinical isolates, as well as protective efficacy against a challenge with RSV A and RSV B strains. Similarly, induction of cross-neutralizing antibodies was observed after immunization with Ad26-encoded preF, preF protein or a mix of both (Ad26/preF protein) in RSV pre-exposed mice and African Green Monkeys. Transfer of serum of human subjects immunized with Ad26/preF protein into cotton rats provide protection against challenges with both RSV A and RSV B, with complete protection against both strains observed in the lower respiratory tract. In contrast, almost no protection against RSV A and B infection was observed after the transfer of a human serum pool isolated pre-vaccination. These results collectively show that the RSV A-based monovalent Ad26/preF protein vaccine induced neutralizing antibodies, as well as protection against both RSV A and RSV B subtypes in animals, including by passive transfer of human antibodies alone, suggesting that clinical efficacy against both subtypes can be achieved. |
| first_indexed | 2024-03-11T05:47:09Z |
| format | Article |
| id | doaj.art-7112a4bed99c4f7a8dfd1dd7c2cab2ec |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-11T05:47:09Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-7112a4bed99c4f7a8dfd1dd7c2cab2ec2023-11-17T14:19:24ZengMDPI AGVaccines2076-393X2023-03-0111367210.3390/vaccines11030672RSV A2-Based Prefusion F Vaccine Candidates Induce RSV A and RSV B Cross Binding and Neutralizing Antibodies and Provide Protection against RSV A and RSV B Challenge in Preclinical ModelsFreek Cox0Eirikur Saeland1Anne Thoma2Ward van den Hoogen3Lisanne Tettero4Joke Drijver5Cornelis Vaneman6Yolinda van Polanen7Tina Ritschel8Arangassery Rosemary Bastian9Benoit Callendret10Roland Zahn11Leslie van der Fits12Janssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The NetherlandsJanssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The NetherlandsJanssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The NetherlandsJanssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The NetherlandsJanssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The NetherlandsJanssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The NetherlandsJanssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The NetherlandsJanssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The NetherlandsJanssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The NetherlandsJanssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The NetherlandsJanssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The NetherlandsJanssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The NetherlandsJanssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The NetherlandsRSV is divided into two antigenic subtypes, RSV A and RSV B, which is largely based on the variation in the G protein, while the fusion protein F is more conserved and a target for antibody-mediated neutralization. Here we evaluate the breadth of the protective immune responses across RSV A and RSV B subtypes, induced by vaccines based on the RSV A-based fusion protein, stabilized in the prefusion conformation (preF) in preclinical models. Immunization of naïve cotton rats with preF subunit or preF encoded by a replication incompetent Adenoviral 26, induced antibodies capable of neutralizing recent RSV A and RSV B clinical isolates, as well as protective efficacy against a challenge with RSV A and RSV B strains. Similarly, induction of cross-neutralizing antibodies was observed after immunization with Ad26-encoded preF, preF protein or a mix of both (Ad26/preF protein) in RSV pre-exposed mice and African Green Monkeys. Transfer of serum of human subjects immunized with Ad26/preF protein into cotton rats provide protection against challenges with both RSV A and RSV B, with complete protection against both strains observed in the lower respiratory tract. In contrast, almost no protection against RSV A and B infection was observed after the transfer of a human serum pool isolated pre-vaccination. These results collectively show that the RSV A-based monovalent Ad26/preF protein vaccine induced neutralizing antibodies, as well as protection against both RSV A and RSV B subtypes in animals, including by passive transfer of human antibodies alone, suggesting that clinical efficacy against both subtypes can be achieved.https://www.mdpi.com/2076-393X/11/3/672Adenoviral vector 26cotton rat modelrespiratory syncytial virusRSV prefusion proteinRSV subtypes |
| spellingShingle | Freek Cox Eirikur Saeland Anne Thoma Ward van den Hoogen Lisanne Tettero Joke Drijver Cornelis Vaneman Yolinda van Polanen Tina Ritschel Arangassery Rosemary Bastian Benoit Callendret Roland Zahn Leslie van der Fits RSV A2-Based Prefusion F Vaccine Candidates Induce RSV A and RSV B Cross Binding and Neutralizing Antibodies and Provide Protection against RSV A and RSV B Challenge in Preclinical Models Vaccines Adenoviral vector 26 cotton rat model respiratory syncytial virus RSV prefusion protein RSV subtypes |
| title | RSV A2-Based Prefusion F Vaccine Candidates Induce RSV A and RSV B Cross Binding and Neutralizing Antibodies and Provide Protection against RSV A and RSV B Challenge in Preclinical Models |
| title_full | RSV A2-Based Prefusion F Vaccine Candidates Induce RSV A and RSV B Cross Binding and Neutralizing Antibodies and Provide Protection against RSV A and RSV B Challenge in Preclinical Models |
| title_fullStr | RSV A2-Based Prefusion F Vaccine Candidates Induce RSV A and RSV B Cross Binding and Neutralizing Antibodies and Provide Protection against RSV A and RSV B Challenge in Preclinical Models |
| title_full_unstemmed | RSV A2-Based Prefusion F Vaccine Candidates Induce RSV A and RSV B Cross Binding and Neutralizing Antibodies and Provide Protection against RSV A and RSV B Challenge in Preclinical Models |
| title_short | RSV A2-Based Prefusion F Vaccine Candidates Induce RSV A and RSV B Cross Binding and Neutralizing Antibodies and Provide Protection against RSV A and RSV B Challenge in Preclinical Models |
| title_sort | rsv a2 based prefusion f vaccine candidates induce rsv a and rsv b cross binding and neutralizing antibodies and provide protection against rsv a and rsv b challenge in preclinical models |
| topic | Adenoviral vector 26 cotton rat model respiratory syncytial virus RSV prefusion protein RSV subtypes |
| url | https://www.mdpi.com/2076-393X/11/3/672 |
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