Challenge Infection of Healthy Adult Volunteers With RSV A2
Condition: Upper Respiratory Tract Infections
MeSH terms: Infections; Communicable Diseases; Respiratory Tract Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      One of the main causes of respiratory infections in children and adults is RSV. This stands
      for respiratory syncytial virus. Healthy adults usually get a cold when they get an infection
      with RSV. They generally recover without any problems. But some infections can be
      life-threatening. Researchers want to study RSV infection in a safe, controlled setting in
      healthy adults to help develop new treatments.

      Objective:

      To test the safety of a high dose of RSV A2 by spraying the virus into the nose, and studying
      how the body responds.

      Eligibility:

      Healthy adults ages 18-50

      Design:

      Participants will be screened during 2 screening visits with:

        -  Medical interview

        -  Physical exam

        -  Blood and nasal samples

        -  Chest X-ray (chest radiograph)

        -  Participants will have a heart test. Sticky patches on the body will detect heart
           electrical activity.

        -  Pulmonary function test (PFT). They will blow into a machine to measure airflow.

        -  Urine tests for pregnancy or drug use.

      Participants will be admitted to the hospital before they get RSV A2.

      Participants will get a single dose of RSV A2 as two sprays, one into each nostril.

      Participants will stay in the hospital under isolation for as long as it takes the body to
      clear RSV A2 from nasal fluids. This can take as long as 14 days or more.

      Participants cannot take any cold medicine to try to feel better.

      Every day, participants will:

        -  Answer questions about their symptoms

        -  Have nasal washes and/or nasal swabs collected

        -  Have a physical exam

      Participants will have blood drawn most days.

      After discharge, participants will keep a health diary.

      Participants will have 2 follow-up visits at 1 month and 2 months after receiving the RSV A2
      dose. A history and physical examination, a blood draw, and nasal wash and swab will be
      performed.
    

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 main purpose of the trial is to define the safety profile,
      determine the frequency of RSV shedding in nasal wash, estimate RSV illness rates, and study
      immune responses in subjects given 1 dose of 10^7 PFU of RSV A2 challenge virus using a nasal
      atomizer. If RSV A2 is found to be sufficiently infectious in adults, then it may be used as
      a challenge virus in future studies evaluating antivirals or the protective efficacy of RSV
      vaccines, or in studies of the immunopathogenesis of RSV infection.

      Subjects will be admitted to the NIH Clinical Center and receive a single intranasal dose of
      10^6.3 PFU or 107 PFU of RSV A2. Subjects will remain at the Clinical Center for
      approximately 9-14 days after challenge infection undergoing sequential clinical evaluations.
      Research specimens, nasal washes and blood, will be collected for various research assays.
      Subjects will be discharged when their daily nasal wash RSV result is negative for two days
      in a row, and they do not have any signs or symptoms suggestive of possible RSV-associated
      lower respiratory tract disease. Subjects will return for follow-up evaluation 28 and 56 days
      after viral challenge.
    

Intervention name(s): 10^6.3 PFU of RSV A2; 10^7 PFU of RSV A2
Intervention type(s): Biological; Biological
Intervention description(s): Each adult volunteer will receive a single intranasal inoculation of 10^6.3 PFU of RSV A2 administered with a nasal atomizer with subsequent sampling of nasal fluids and blood draws.; Each adult volunteer will receive a single intranasal inoculation of 10^7 PFU of RSV A2 administered with a nasal atomizer with subsequent sampling of nasal fluids and blood draws.
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: RSV Shedding; Immune Responses; Neutralizing Antibody Titer; Upper Respiratory Tract Infection