Live Respiratory Syncytial Virus Attenuated by M2-2 Deletion and Stabilized Temperature Sensitivity Mutation 1030s Is a Promising Vaccine Candidate in Children

• Published in: The Journal of infectious diseases Vol. 221; no. 4; pp. 534 - 543
• Main Authors: McFarland, Elizabeth J, Karron, Ruth A, Muresan, Petronella, Cunningham, Coleen K, Libous, Jennifer, Perlowski, Charlotte, Thumar, Bhagvanji, Gnanashanmugam, Devasena, Moye, Jack, Schappell, Elizabeth, Barr, Emily, Rexroad, Vivian, Fearn, Laura, Spector, Stephen A, Aziz, Mariam, Cielo, Mikhaela, Beneri, Christy, Wiznia, Andrew, Luongo, Cindy, Collins, Peter, Buchholz, Ursula J
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 03-02-2020
• Subjects: Antibodies; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Body Temperature; Children; COVID-19 vaccines; Double-Blind Method; Female; Fever; Gene Deletion; Genomic instability; Humans; Immunogenicity; Immunogenicity, Vaccine; Infant; Infectivity; Major and Brief Reports; Male; Mutation; Pediatrics; Point Mutation; Polymerase chain reaction; Protein biosynthesis; Respiratory syncytial virus; Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus Infections - prevention & control; Respiratory Syncytial Virus Infections - virology; Respiratory Syncytial Virus Vaccines - adverse effects; Respiratory Syncytial Virus Vaccines - immunology; Respiratory Syncytial Virus, Human - genetics; Respiratory Syncytial Virus, Human - immunology; Rhinovirus; RNA-Dependent RNA Polymerase - genetics; Vaccination; Vaccines; Vaccines, Attenuated; Viral Proteins - genetics; Virus Replication - genetics; Wheezing; neutralizing antibodies; respiratory syncytial virus (RSV); live-attenuated viral vaccine; RNA regulatory protein M2-2; pediatric RSV vaccine
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiz603

Abstract
Background
The safety and immunogenicity of live respiratory syncytial virus (RSV) candidate vaccine, LID/ΔM2-2/1030s, with deletion of RSV ribonucleic acid synthesis regulatory protein M2-2 and genetically stabilized temperature-sensitivity mutation 1030s in the RSV polymerase protein was evaluated in RSV-seronegative children.
Methods
Respiratory syncytial virus-seronegative children ages 6–24 months received 1 intranasal dose of 105 plaque-forming units (PFU) of LID/ΔM2-2/1030s (n = 21) or placebo (n = 11). The RSV serum antibodies, vaccine shedding, and reactogenicity were assessed. During the following RSV season, medically attended acute respiratory illness (MAARI) and pre- and postsurveillance serum antibody titers were monitored.
Results
Eighty-five percent of vaccinees shed LID/ΔM2-2/1030s vaccine (median peak nasal wash titers: 3.1 log10 PFU/mL by immunoplaque assay; 5.1 log10 copies/mL by reverse-transcription quantitative polymerase chain reaction) and had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms and fever were common (60% vaccinees and 27% placebo recipients). One vaccinee had grade 2 wheezing with rhinovirus but without concurrent LID/ΔM2-2/1030s shedding. Five of 19 vaccinees had ≥4-fold increases in antibody titers postsurveillance without RSV-MAARI, indicating anamnestic responses without significant illness after infection with community-acquired RSV.
Conclusions
LID/ΔM2-2/1030s had excellent infectivity without evidence of genetic instability, induced durable immunity, and primed for anamnestic antibody responses, making it an attractive candidate for further evaluation.
Live respiratory syncytial virus (RSV) vaccine LID/∆M2-2/1030s attenuated by deletion of the RNA regulatory protein M2-2 and temperature-sensitivity mutation 1030s had excellent immunogenicity and genetic stability in RSV-seronegative 6- to 24-month-old children, making it an attractive candidate for further evaluation.