Live respiratory syncytial virus (RSV) vaccine candidate containing stabilized temperature-sensitivity mutations is highly attenuated in RSV-seronegative infants and children

Ursula J. Buchholz, Coleen K. Cunningham, Petronella Muresan, Devasena Gnanashanmugam, Paul Sato, George K. Siberry, Vivian Rexroad, Megan Valentine, Charlotte Perlowski, Elizabeth Schappell, Bhagvinji Thumar, Cindy Luongo, Emily Barr, Mariam Aziz, Ram Yogev, Stephen A. Spector, Peter L. Collins, Elizabeth J. McFarland, Ruth A. Karron

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1338-1346
Number of pages9
JournalJournal of Infectious Diseases
Volume217
Issue number9
DOIs
StatePublished - May 1 2018

Keywords

  • Pediatric vaccine
  • Recombinant live-attenuated vaccine
  • Respiratory syncytial virus
  • Respiratory virus infection
  • Reverse genetics

ASJC Scopus subject areas

  • General Medicine

Fingerprint

Dive into the research topics of 'Live respiratory syncytial virus (RSV) vaccine candidate containing stabilized temperature-sensitivity mutations is highly attenuated in RSV-seronegative infants and children'. Together they form a unique fingerprint.

Cite this