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Updated: May 9, 2026
Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
Experimental infection of adults with recombinant wild-type human metapneumovirus
Kawsar R Talaat1, Ruth A Karron, Bhagvanji Thumar
1Center for Immunization Research, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore.
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.
Insights
Recombinant human metapneumovirus (rHMPV-SHs) showed infectivity and immunogenicity in healthy adults, supporting its use as a parent virus for live-attenuated HMPV vaccine development.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Human metapneumovirus (HMPV) is a significant cause of lower respiratory tract infections in young children.
- Recombinant HMPV (rHMPV-SHs) is derived from a wild-type HMPV strain.
- Characterizing rHMPV-SHs infectivity and immunogenicity is crucial for developing live-attenuated HMPV vaccines.
Purpose of the Study:
- To assess the infectivity and immunogenicity of rHMPV-SHs in healthy adults.
- To determine the suitability of rHMPV-SHs as a parent virus for live-attenuated HMPV vaccine candidates.
Main Methods:
- Twenty-one healthy adults received intranasal inoculation of rHMPV-SHs.
- Respiratory symptoms, viral shedding, and antibody responses (neutralizing, IgG, IgA) were measured.
- Nasal cytokine induction was assessed using electrochemiluminescence assays.
Main Results:
- 43% of subjects were infected, with peak viral shedding on days 7-9.
- 35% of subjects developed an antibody response four weeks post-inoculation.
- Infected subjects experienced respiratory symptoms and headache; cytokine patterns varied.
Conclusions:
- rHMPV-SHs demonstrates infectivity and immunogenicity in humans.
- This recombinant virus is a suitable candidate for developing live-attenuated HMPV vaccines.
