Experimental infection of adultswith recombinantwild-type human metapneumovirus

Kawsar Rasmy Talaat, Ruth A Karron, Bhagvanji Thumar, Bridget A. McMahon, Alexander C. Schmidt, Peter L. Collins, Ursula J. Buchholz

Research output: Contribution to journalArticle

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 106 plaque-forming units of rHMPVSHs. 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.

Original languageEnglish (US)
Pages (from-to)1669-1678
Number of pages10
JournalJournal of Infectious Diseases
Volume208
Issue number10
DOIs
StatePublished - Nov 15 2013

Fingerprint

Metapneumovirus
Virus Shedding
Viruses
Antibody Formation
Infection
Nose
Immunoglobulin A
Cytokines
Attenuated Vaccines
Synthetic Vaccines
Neutralizing Antibodies
Serum
Respiratory Tract Infections
Headache
Vaccines
Immunoglobulin G
Clinical Trials
Antibodies

Keywords

  • Challenge
  • HMPV
  • Human metapneumovirus

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy
  • Medicine(all)

Cite this

Experimental infection of adultswith recombinantwild-type human metapneumovirus. / Talaat, Kawsar Rasmy; Karron, Ruth A; Thumar, Bhagvanji; McMahon, Bridget A.; Schmidt, Alexander C.; Collins, Peter L.; Buchholz, Ursula J.

In: Journal of Infectious Diseases, Vol. 208, No. 10, 15.11.2013, p. 1669-1678.

Research output: Contribution to journalArticle

Talaat, Kawsar Rasmy ; Karron, Ruth A ; Thumar, Bhagvanji ; McMahon, Bridget A. ; Schmidt, Alexander C. ; Collins, Peter L. ; Buchholz, Ursula J. / Experimental infection of adultswith recombinantwild-type human metapneumovirus. In: Journal of Infectious Diseases. 2013 ; Vol. 208, No. 10. pp. 1669-1678.
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