title: Evaluation of a live, cold-passaged, temperature-sensitive, respiratory syncytial virus vaccine candidate in infancy.
abstract: A live-attenuated, intranasal respiratory syncytial virus (RSV) candidate vaccine, cpts-248/404, was tested in phase 1 trials in 114 children, including 37 1-2-month-old infants-a target age for RSV vaccines. The cpts-248/404 vaccine was infectious at 104 and 105 plaque-forming units in RSV-naive children and was broadly immunogenic in children >6 months old. Serum and nasal antibody responses in 1-2 month olds were restricted to IgA, had a dominant response to RSV G protein, and had no increase in neutralizing activity. Nevertheless, there was restricted virus shedding on challenge with a second vaccine dose and preliminary evidence for protection from symptomatic disease on natural reexposure. The cpts-248/404 vaccine candidate did not cause fever or lower respiratory tract illness. In the youngest infants, however, cpts-248/404 was unacceptable because of upper respiratory tract congestion associated with peak virus recovery. A live attenuated RSV vaccine for the youngest infant will use cpts-248/404 modified by additional attenuating mutations.
authors.affiliation: Division of Infectious Disease, Dept. of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. peter.wright@mcmail.vanderbilt.edu
authors.forename: P F
authors.initials: PF
authors.lastname: Wright
authors.forename: R A
authors.initials: RA
authors.lastname: Karron
authors.forename: R B
authors.initials: RB
authors.lastname: Belshe
authors.forename: J
authors.initials: J
authors.lastname: Thompson
authors.forename: J E
authors.initials: JE
authors.lastname: Crowe
authors.forename: T G
authors.initials: TG
authors.lastname: Boyce
authors.forename: L L
authors.initials: LL
authors.lastname: Halburnt
authors.forename: G W
authors.initials: GW
authors.lastname: Reed
authors.forename: S S
authors.initials: SS
authors.lastname: Whitehead
authors.forename: E L
authors.initials: EL
authors.lastname: Anderson
authors.forename: A E
authors.initials: AE
authors.lastname: Wittek
authors.forename: R
authors.initials: R
authors.lastname: Casey
authors.forename: M
authors.initials: M
authors.lastname: Eichelberger
authors.forename: B
authors.initials: B
authors.lastname: Thumar
authors.forename: V B
authors.initials: VB
authors.lastname: Randolph
authors.forename: S A
authors.initials: SA
authors.lastname: Udem
authors.forename: R M
authors.initials: RM
authors.lastname: Chanock
authors.forename: B R
authors.initials: BR
authors.lastname: Murphy
mesh_terms: D000914:Antibodies, Viral / Q000097:blood; D001942:Breast Feeding; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007114:Immunization; D007070:Immunoglobulin A / Q000097:blood; D007223:Infant; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013696:Temperature; D014613:Vaccines, Attenuated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*; D017201:Virus Shedding
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D014613:Vaccines, Attenuated; D014765:Viral Vaccines