Live Respiratory Syncytial Virus (RSV) Vaccine Candidate Containing Stabilized Temperature-Sensitivity Mutations Is Highly Attenuated in RSV-Seronegative Infants and Children
| Autor: | Megan Valentine, Emily Barr, Petronella Muresan, Cindy Luongo, Ruth A. Karron, Coleen K. Cunningham, Peter L. Collins, Vivian Rexroad, Devasena Gnanashanmugam, Elizabeth Schappell, Ursula J. Buchholz, Ram Yogev, George K. Siberry, Bhagvinji Thumar, Stephen A. Spector, Mariam Aziz, Charlotte Perlowski, Paul A. Sato, Elizabeth J. McFarland |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male viruses Respiratory Syncytial Virus Infections medicine.disease_cause Antibodies Viral Vaccines Attenuated Virus Replication Virus 03 medical and health sciences Major Articles and Brief Reports Immunogenicity Vaccine Respiratory Syncytial Virus Vaccines Immunology and Allergy Medicine Humans Neutralizing antibody Reactogenicity biology business.industry Infant Virology Antibodies Neutralizing Vaccination Titer 030104 developmental biology Infectious Diseases Respiratory syncytial virus (RSV) Respiratory Syncytial Virus Human Mutation biology.protein Female Antibody business |
| Zdroj: | The Journal of infectious diseases. 217(9) |
| ISSN: | 1537-6613 |
| Popis: | BACKGROUND: Respiratory syncytial virus (RSV) is the most important viral cause of severe respiratory illness in young children and lacks a vaccine. RSV cold-passage/stabilized 2 (RSVcps2) is a modification of a previously evaluated vaccine candidate in which 2 major attenuating mutations have been stabilized against deattenuation. METHODS: RSV-seronegative 6–24-month-old children received an intranasal dose of 10(5.3) plaque-forming units (PFU) of RSVcps2 (n = 34) or placebo (n = 16) (International Maternal Pediatric Adolescent AIDS Clinical Trials protocol P1114 and companion protocol CIR285). RSV serum neutralizing antibody titers before and 56 days after vaccination, vaccine virus infectivity (defined as vaccine virus shedding detectable in nasal wash and/or a ≥4-fold rise in serum antibodies), reactogenicity, and genetic stability were assessed. During the following RSV transmission season, participants were monitored for respiratory illness, with serum antibody titers measured before and after the season. RESULTS: A total of 85% of vaccinees were infected with RSVcps2 (median peak titer, 0.5 log(10) PFU/mL by culture and 2.9 log(10) copies/mL by polymerase chain reaction analysis); 77% shed vaccine virus, and 59% developed a ≥4-fold rise in RSV-serum neutralizing antibody titers. Respiratory tract and/or febrile illness occurred at the same rate (50%) in the vaccine and placebo groups. Deattenuation was not detected at either of 2 stabilized mutation sites. CONCLUSIONS: RSVcps2 was well tolerated and moderately immunogenic and had increased genetic stability in 6–24-month-old RSV-seronegative children. CLINICAL TRIALS REGISTRATION: NCT01852266 and NCT01968083. |
| Databáze: | OpenAIRE |
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