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.

Inclusion Criteria:

• General good health, without significant medical illness, physical examination findings, or significant laboratory abnormalities as determined by the investigator
• Available for the duration of the trial
• Female subjects must agree to use effective birth control methods for the duration of the study

Exclusion Criteria:

• Pregnant
• Currently breastfeeding
• Evidence of clinically significant diseases in the nervous system, heart, lungs, liver, autoimmune system, or kidney or involving rheumatism, as determined by medical history, physical examination, or laboratory studies, including urine testing.
• Clinically significant alanine aminotransferase (ALT) levels, as determined by the principal investigator (PI)
• Behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, affects the ability to understand and cooperate with the study protocol
• Human metapneumovirus (HMPV) specific serum immunoglobulin A (IgA) titer greater than 1:50
• HMPV-specific nasal wash IgA titer greater than 1:50
• Positive urine drug toxicology test indicating narcotic use
• Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months
• Other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a subject participating in the trial or would render the subject unable to comply with the protocol
• History of hypersensitivity reactions
• Diagnosis of asthma or reactive airway disease within the past 2 years
• Positive result on test for HIV
• Positive result on test for hepatitis C virus (HCV)
• Positive result on test for hepatitis B virus surface antigen (HBsAg)
• Known immunodeficiency syndrome
• Use of corticosteroids (excluding topical or nasal preparations) or immunosuppressive drugs within 30 days prior to inoculation
• Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to inoculation with challenge virus, rHMPV-SHs
• History of a surgical removal of the spleen
• Receipt of blood or blood-derived products (including immunoglobulin) within 6 months prior to study inoculation
• Current smoker unwilling to stop smoking for the duration of the study
• Receipt of another investigational vaccine or drug within 30 days prior to study inoculation
• Body mass index (BMI) greater than 35
• Shares household with a child younger than 60 months of age or an immunocompromised individual
• Unwillingness to have nasal wash or blood samples saved for future respiratory virus research