title: Experimental infection of adults with recombinant wild-type human metapneumovirus.
abstract: BACKGROUND
  Human metapneumovirus (HMPV) causes lower respiratory tract infections in young children. rHMPV-SHs is a recombinant HMPV (rHMPV) based on a biologically derived wild-type HMPV strain. We characterized its infectivity and immunogenicity in healthy adults to determine whether it would be suitable for use as the parent virus for the development of live attenuated rHMPV vaccines.
  
  
  METHODS
  Twenty-one healthy adults were inoculated intranasally with 10(6) plaque-forming units of rHMPV-SHs. Respiratory symptoms and shedding of challenge virus were assessed. Neutralizing antibody responses, serum immunoglobulin G and A, and nasal wash specimen immunoglobulin A antibody responses to the HMPV F protein were also measured. Induction of nasal cytokines was assessed with electrochemiluminescence assays.
  
  
  RESULTS
  Nine subjects (43%) were infected with challenge virus as determined by virus detection and/or ≥4-fold rise in serum antibody titers. Peak viral shedding occurred on days 7-9 after infection. Four weeks after inoculation, 35% of subjects had any antibody response. Six of 9 infected subjects had respiratory symptoms, and 3 had headache after inoculation. Cytokine patterns differed considerably between subjects with similar illness severity and viral shedding.
  
  
  CONCLUSIONS
  The rHMPV-SHs virus is infectious and is a suitable parent virus for development of live-attenuated HMPV vaccine candidates. Clinical Trials Registration. NCT01109329.
authors.affiliation: Center for Immunization Research, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore.
authors.forename: Kawsar R
authors.initials: KR
authors.lastname: Talaat
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Karron
authors.forename: Bhagvanji
authors.initials: B
authors.lastname: Thumar
authors.forename: Bridget A
authors.initials: BA
authors.lastname: McMahon
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Schmidt
authors.forename: Peter L
authors.initials: PL
authors.lastname: Collins
authors.forename: Ursula J
authors.initials: UJ
authors.lastname: Buchholz
mesh_terms: D000328:Adult; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D029121:Metapneumovirus / Q000235:genetics / Q000276:immunology*; D018184:Paramyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D012141:Respiratory Tract Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D019562:Viral Load; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology; D017201:Virus Shedding
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D014613:Vaccines, Attenuated; D014765:Viral Vaccines
keywords: HMPV; challenge; human metapneumovirus
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