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.

作者信息

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

机构信息

Janssen Vaccines & Prevention B.V. Archimedesweg 4-6, 2333 CN Leiden, The Netherlands.

出版信息

Vaccines (Basel). 2023 Mar 16;11(3):672. doi: 10.3390/vaccines11030672.

Abstract

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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bec1/10057437/5a798d6d5709/vaccines-11-00672-g001.jpg

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