An RSV Live-Attenuated Vaccine Candidate Lacking G Protein Mucin Domains Is Attenuated, Immunogenic, and Effective in Preventing RSV in BALB/c Mice

• Authors: Xuemin Chen, Emory University; Martin Moore, Emory University; Michael Koval, Emory University; Larry Anderson, Emory University; Evan Anderson, Emory University; Christina Rostad, Emory University; Bo Liang, Emory University; Anne Piantadosi, Emory University; MK Roe, Butler University; MA Perez, Emory University; H-M Hsiao, Emory University; SA Lapp, Emory University; H-Y Sun, Emory University; S Jadhao, Emory University; AR Young, Butler University; YS Batista, Butler University; RC Reed, Emory University; A Taz, Emory University; TA Snider, Oklahoma State Univ; CC Stobart, Butler University
• Journal Title: JOURNAL OF INFECTIOUS DISEASES
• Volume: Volume 227, Number 1
• Publisher: OXFORD UNIV PRESS INC | 2022-10-25, Pages 50-60
• Type of Work: Article
• Publisher DOI: http://doi.org/10.1093/infdis/jiac382
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Infectious Diseases; Microbiology; RSV; glycoprotein; glycosylation; live-attenuated vaccine; mucin domains; pediatric; RESPIRATORY SYNCYTIAL VIRUS; REVERSE GENETICS; FUSION PROTEIN; REPLICATION; DISEASE

Abstract

Background. Respiratory syncytial virus (RSV) is a leading viral respiratory pathogen in infants. The objective of this study was to generate RSV live-attenuated vaccine (LAV) candidates by removing the G-protein mucin domains to attenuate viral replication while retaining immunogenicity through deshielding of surface epitopes. Methods. Two LAV candidates were generated from recombinant RSV A2-line19F by deletion of the G-protein mucin domains (A2-line19F-G155) or deletion of the G-protein mucin and transmembrane domains (A2-line19F-G155S). Vaccine attenuation was measured in BALB/c mouse lungs by fluorescent focus unit (FFU) assays and real-time polymerase chain reaction (RT-PCR). Immunogenicity was determined by measuring serum binding and neutralizing antibodies in mice following prime/boost on days 28 and 59. Efficacy was determined by measuring RSV lung viral loads on day 4 postchallenge. Results. Both LAVs were undetectable in mouse lungs by FFU assay and elicited similar neutralizing antibody titers compared to A2-line19F on days 28 and 59. Following RSV challenge, vaccinated mice showed no detectable RSV in the lungs by FFU assay and a significant reduction in RSV RNA in the lungs by RT-PCR of 560-fold for A2-line19F-G155 and 604-fold for A2-line19FG155S compared to RSV-challenged, unvaccinated mice. Conclusions. Removal of the G-protein mucin domains produced RSV LAV candidates that were highly attenuated with retained immunogenicity.