title: Evaluation of the live attenuated cpts 248/404 RSV vaccine in combination with a subunit RSV vaccine (PFP-2) in healthy young and older adults.
abstract: The safety and immunogenicity of the live attenuated cold-passaged, temperature-sensitive (cpts) 248/404 respiratory syncytial virus (RSV) A2 and the RSV A2 purified F glycoprotein (PFP-2) vaccine candidates were evaluated in a placebo-controlled trial in 60 healthy young adults and 60 healthy elderly subjects using simultaneous and sequential (cpts 248/404 followed by PFP-2) vaccination schedules. Both vaccines were well tolerated. The cpts 248/404 vaccine was moderately infectious in both young and old volunteers, but was highly restricted in replication in those who were infected. After both vaccines, RSV neutralizing antibody (neut Ab) titers increased fourfold in 22% of young subjects and in 16% of elderly subjects. Of those with low levels of RSV neut Ab (titer <9), 10/12 (83% of) young subjects and six/eight (75% of) elderly subjects had a >/=four fold rise in neut Ab titer. Young and elderly subjects immunized simultaneously had similar serum IgG and IgA postimmunization titers to RSV F (IgG, 16.4 vs 16.2, IgA 11.6 vs 12. 5, respectively) as did those who were immunized sequentially (IgG 17.4 vs 17.0, IgA 13.0 vs 13.5). In both age groups, sequential immunization elicited higher postimmunization RSV F IgG and IgA titers than simultaneous immunization. Further studies that combine the PFP-2 subunit vaccine with a less attenuated RSV vaccine should be performed.
authors.affiliation: Division of Disease Control, Department of International Health, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: I M
authors.initials: IM
authors.lastname: Gonzalez
authors.forename: R A
authors.initials: RA
authors.lastname: Karron
authors.forename: M
authors.initials: M
authors.lastname: Eichelberger
authors.forename: E E
authors.initials: EE
authors.lastname: Walsh
authors.forename: V W
authors.initials: VW
authors.lastname: Delagarza
authors.forename: R
authors.initials: R
authors.lastname: Bennett
authors.forename: R M
authors.initials: RM
authors.lastname: Chanock
authors.forename: B R
authors.initials: BR
authors.lastname: Murphy
authors.forename: M L
authors.initials: ML
authors.lastname: Clements-Mann
authors.forename: A R
authors.initials: AR
authors.lastname: Falsey
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004334:Drug Administration Schedule; D005260:Female; D015707:HN Protein; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects / Q000276:immunology; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology / Q000821:virology; D012044:Regression Analysis; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D014764:Viral Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D015707:HN Protein; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D014765:Viral Vaccines; C116204:attachment protein G