Respiratory Syncytial Virus Human Challenge in Healthy Adult Volunteers
Condition: Upper Respiratory Tract Infection
MeSH terms: Respiratory Tract Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - Respiratory syncytial virus (RSV) can cause respiratory infections. Some of these can be
      life-threatening, especially in young children, the elderly, and people with weak immune
      systems. Researchers want to study RSV infection in a hospital setting in healthy adults.
      They want to use what they learn to test new treatments or vaccines in the future.

      Objectives:

      - To study how the body responds to RSV.

      Eligibility:

      - Healthy volunteers ages 18-50

      Design:

        -  Participants will be screened under another protocol.

        -  Participants will have:

        -  Medical history

        -  Physical exams

        -  EKG. Heart rhythm is measured with small sticky patches on the chest, arms, and legs.

        -  Chest x-ray

        -  Pulmonary function tests. This measures how much air a person can move into and out of
           the lungs.

        -  Blood and urine tests

        -  Nasal washes and/or nasal swabs. For the wash, the nose will be rinsed with a sterile
           liquid. For the swab, the inside of the nostril will be rubbed with a cotton swab.

        -  Participants will have two, possibly three, follow-up outpatient visits, approximately
           1, 2 and 6 months after receiving the dose of RSV.

        -  Participants will stay in the hospital under isolation for 7 or more days after getting
           the virus.

        -  The average stay is 10 days. Participants cannot leave the isolation unit. They cannot
           have visitors.

        -  The virus should cause a mild to medium cold.

        -  Participants will fill out a symptom card every day in the hospital and for 1 month
           after.

        -  Participants will have 2 follow-up visits, 28 and 56 days after leaving the hospital.

        -  Female participants who are sexually active must remain abstinent or use an effective
           form of birth control for 1 month before and after getting the virus.
    

Detailed description: 
      Respiratory syncytial virus (RSV) is the leading cause of pediatric lower respiratory tract
      infection. RSV also causes lower respiratory tract disease in the elderly and
      life-threatening disease in immunocompromised hosts. An RSV monoclonal antibody (palivizumab)
      is currently available for passive immunoprophylaxis in high-risk infants. Vaccines and
      antiviral agents are under development for the treatment and prevention of RSV, but none are
      licensed. The ability to challenge healthy volunteers with RSV could rapidly facilitate
      efficacy studies of future antivirals and vaccines. In addition, challenge studies would
      provide critical information on viral pathogenesis, including types of cells infected,
      mucosal and systemic immune response, and alterations in respiratory microbiota. Clinical
      trial material for human challenge studies has been prepared from live recombinant
      (complementary DNA-derived) RSV of subgroup A (RSV A2).

      This study will be a phase 1 study in healthy adult male and non-pregnant female subjects 18
      years to 50 years of age. The purpose of the trial is to define safety profiles and estimate
      illness rates for subjects given 2 different doses of RSV A2 challenge virus. If RSV A2 is
      found to be sufficiently infectious in adults, then it may be used as a challenge virus in
      future studies evaluating the protective efficacy of RSV vaccines or antivirals and in
      studies of pathogenesis of RSV.

      Subjects will be admitted to the NIH Clinical Center and receive a single intranasal dose of
      RSV A2 at either 10^5 or 10^6.3 PFU. Subjects will remain at the Clinical Center for
      approximately 9-12 days for clinical evaluation. Research procedures conducted on blood and
      nasal swab and wash samples will include lymphocyte phenotyping, cytokine analysis,
      transcriptosome profiling, RSV-specific immunoglobin analysis (circulating IgG and nasal
      secretory IgA), quantitative viral titers and viral culture, and nasal microbiome analysis.
      Subjects will be discharged when their NP wash RSV results are negative for two consecutive
      days and they do not have any signs or symptoms suggestive of possible RSV-associated lower
      respiratory tract disease. Subjects will return for followup evaluation 28 and 56 days after
      viral challenge.
    

Intervention name(s): RSV A2
Intervention type(s): Biological
Intervention description(s): Intranasal inoculation of healthy volunteers with 10^5 or 10^6.3 plaque forming units (PFU) of RSV A2.
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Neutralizing Antibody; Viral Shedding; Challenge; RSV; Healthy Volunteer