1. Codon-optimization of the respiratory syncytial virus (RSV) G protein expressed in a vesicular stomatitis virus (VSV) vector improves immune responses in a cotton rat model.
- Author
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Brakel KA, Ma Y, Binjawadagi R, Harder O, Watts M, Li J, Binjawadagi B, and Niewiesk S
- Subjects
- Animals, Antibodies, Neutralizing, Antibodies, Viral, Codon, GTP-Binding Proteins, Immunity, Sigmodontinae, Vesicular stomatitis Indiana virus, Vesiculovirus genetics, Viral Fusion Proteins genetics, Respiratory Syncytial Virus Infections, Respiratory Syncytial Virus Vaccines genetics, Respiratory Syncytial Virus, Human genetics, Vesicular Stomatitis
- Abstract
Respiratory syncytial virus is an important cause of pneumonia in children, the elderly, and immunocompromised individuals. The attachment (G) protein of RSV generates neutralizing antibodies in natural RSV infection which correlate with protection against disease. The immune response to RSV is typically short-lived, which may be related to the heavy glycosylation of RSV-G. In order to improve its immunogenicity, we expressed G protein mutants in a vesicular stomatitis virus (VSV) vector system and tested their ability to protect cotton rats from RSV challenge. We found that the most protective construct was codon-optimized RSV-G, followed by wild-type G and membrane-bound G. Constructs which expressed the G protein with reduced glycosylation or the secreted G protein provided either partial or no protection. Our results demonstrate that modifications to the G protein are not advantageous in a VSV vector system, and that an intact, codon-optimized G is a superior vaccine candidate., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
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