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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.
Cox, Freek; Saeland, Eirikur; Thoma, Anne; van den Hoogen, Ward; Tettero, Lisanne; Drijver, Joke; Vaneman, Cornelis; van Polanen, Yolinda; Ritschel, Tina; Bastian, Arangassery Rosemary; Callendret, Benoit; Zahn, Roland; van der Fits, Leslie.
Afiliação
  • Cox F; Janssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
  • Saeland E; Janssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
  • Thoma A; Janssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
  • van den Hoogen W; Janssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
  • Tettero L; Janssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
  • Drijver J; Janssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
  • Vaneman C; Janssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
  • van Polanen Y; Janssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
  • Ritschel T; Janssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
  • Bastian AR; Janssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
  • Callendret B; Janssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
  • Zahn R; Janssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
  • van der Fits L; Janssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.
Vaccines (Basel) ; 11(3)2023 Mar 16.
Article em En | MEDLINE | ID: mdl-36992257
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article