Live-Attenuated Respiratory Syncytial Virus Vaccine With Deletion of RNA Synthesis Regulatory Protein M2-2 and Cold Passage Mutations Is Overattenuated.

Autor: Cunningham CK; Department of Pediatrics, Duke University Medical Center, Durham, North Carolina., Karron R; Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland., Muresan P; Statistical & Data Analysis Center, Harvard T.H. Chan School of Public Health/Frontier Science, Boston, Massachusetts., McFarland EJ; Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, Colorado., Perlowski C; FHI 360, Durham, North Carolina., Libous J; FHI 360, Durham, North Carolina., Thumar B; Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland., Gnanashanmugam D; Maternal, Adolescent and Pediatric Research Branch, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland., Moye J Jr; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland., Schappell E; Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland., Barr E; Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, Colorado., Rexroad V; Investigational Drug Service Pharmacy, Johns Hopkins Hospital, Baltimore, Maryland., Aziz M; Section of Infectious Disease, Rush University Medical Center, Chicago, Illinois., Deville J; Division of Pediatric Infectious Diseases, University of California, Los Angeles, California., Rutstein R; Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Yang L; Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland., Luongo C; Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland., Collins P; Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland., Buchholz U; Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
Jazyk: angličtina
Zdroj: Open forum infectious diseases [Open Forum Infect Dis] 2019 May 06; Vol. 6 (6), pp. ofz212. Date of Electronic Publication: 2019 May 06 (Print Publication: 2019).
DOI: 10.1093/ofid/ofz212
Abstrakt: Background: The live respiratory syncytial virus (RSV) candidate vaccine LIDcpΔM2-2 is attenuated through deletion of M2-2 and 5 cold-passage mutations.
Methods: RSV-seronegative children aged 6-24 months received a single intranasal dose of 10 5 plaque-forming units (PFU) of LIDcpΔM2-2 or placebo. RSV serum antibodies, vaccine infectivity, and reactogenicity were assessed.
Results: Four of 11 (36%) vaccinees shed vaccine virus with median peak titers of 1.6 log 10 PFU/mL by quantitative culture and 4.5 log 10 copies/mL by polymerase chain reaction; 45% had ≥4-fold rise in serum-neutralizing antibodies. Respiratory symptoms or fever were common in vaccinees (64%) and placebo recipients (6/6, 100%).
Conclusions: RSV LIDcpΔM2-2 is overattenuated. Clinical Trial Numbers.  NCT02890381, NCT02948127.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje