Human metapneumovirus (HMPV) is a virus that can cause respiratory illness. In older adults, those with asthma, infants, and children, illness can be severe, but in healthy adults the virus frequently causes no symptoms. The National Institute of Allergy and Infectious Diseases (NIAID) is working to develop a vaccine for HMPV that could be given to infants. Before potential vaccines can be tested, information about how HMPV affects healthy adults is needed. This study will examine the effects of exposure to HMPV in healthy adults.
Human metapneumovirus (HMPV), a virus that causes respiratory illness, was first discovered in 2001, although humans have been infected with it for at least 50 years. HMPV may cause upper respiratory illness or no symptoms at all in healthy adults, but older adults, adults with asthma, and children may be at risk of more serious illness. HMPV is a leading cause of viral lower respiratory infection (LRI) in children, so finding a vaccine for this virus could substantially reduce the instances of childhood respiratory illnesses. The National Institute of Allergy and Infectious Diseases (NIAID) is developing a vaccine for HMPV for use in infants, but before starting clinical trials with potential HMPV vaccines, researchers need to study how wild HMPV affects healthy adults. This study will expose healthy adults to a dose of the HMPV virus to assess its ability to infect, cause disease, and create an immune system response. Participation in this study will last approximately 6 months. Participants will be admitted to an inpatient unit, where they will stay for 10 full days. On their second day in the unit, participants will receive a single dose of the virus, delivered via nose drops. Twice each day while participants are inpatients, they will undergo physical exams and have their vital signs recorded. Nasal washes and blood samples will be collected before participants receive the virus, and then daily nasal washes will be collected until they are discharged from the inpatient unit. Participants will be discharged from the unit on the 9th day after receiving virus if their nasal wash from Day 8 was free of virus. Follow-up visits will occur 28, 120, and 180 days after participants receive the virus. During follow-up visits nasal washes and blood samples will be collected.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
Single dose of 10\^6 plaque forming units (PFU) of recombinant HMPV small hydrophobic genes (rHMPV-SHs)
Johns Hopkins Bloomberg School of Public Health
Baltimore, Maryland, United States
Frequency of challenge virus (rHMPV-SHs) infection, defined as virus shedding in respiratory secretions or serological evidence of HMPV infection
Time frame: Measured at baseline and on Days 1 to 9
rHMPV-SHs shedding, as measured by peak virus titer, mean sum of daily virus titers, and total duration of shedding
Time frame: Measured at baseline and on Days 1 to 9
Frequency and severity of respiratory illness
Time frame: Measured at study completion
Magnitude, frequency, and duration of serum and nasal wash antibody responses induced by rHMPV-SHs
Time frame: Measured at baseline and on Days 28, 120, and 180
Correlation between virus shedding and severity of clinical illness
Time frame: Measured at study completion
Cytokine and chemokine concentrations in nasal wash samples and relationships between cytokine/chemokine induction, viral replication, and illness
Time frame: Measured at study completion
T-cell mediated and innate immune responses
Time frame: Measured at baseline and on Days 8, 28, and 180
Whether HMPV infection induces characteristic gene expression patterns in cells obtained from blood or nasal wash
Time frame: Measured at baseline and Days 3, 5, 7, 8, 28, and 180
Relationship between the development of immune responses and clearance of rHMPV-SHs
Time frame: Measured at study completion
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PREVENTION
Masking
NONE
Enrollment
21