Challenge Infection of Healthy Adult Volunteers With RSV A2
Condition: Upper Respiratory Tract Infections
MeSH terms: Infections; Communicable Diseases; Respiratory Tract Infections
Intervention: 10^6.3 PFU of RSV A2; 10^7 PFU of RSV A2
Intervention description: 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.
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: RSV Shedding; Immune Responses; Neutralizing Antibody Titer; Upper Respiratory Tract Infection

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Age 18-50 years inclusive.

               2. General good health, without significant medical illness, physical exam findings,
                  or significant laboratory abnormalities as determined by the investigator.

               3. Willingness to stay confined to the inpatient unit for required study duration.

               4. Willingness to have samples stored for future research.

               5. Subjects must be of non-childbearing potential (e.g., surgically sterilized
                  (bilateral oophorectomy, bilateral tubal ligation, hysterectomy) or, if of
                  child-bearing potential and sexually active with a partner who can get them
                  pregnant, must have in place an effective method of contraception for at least 30
                  days prior to administration of the challenge virus and until 30 days after
                  challenge virus

                  administration:

                    -  intrauterine device (IUD) or equivalent

                    -  hormonal contraceptives (e.g., consistent, continuous use of contraceptive
                       pill, patch, ring, implant, or injection)

                       ---if participant uses contraceptive pill, patch, or ring, they must also
                       use a barrier method at the time of potentially reproductive sexual activity
                       (e.g., (male/female condom, cap, or diaphragm) plus spermicide)

                    -  be in a monogamous relationship with a partner who has undergone a vasectomy
                       at least 180 days prior to first dose of study agent

               6. A plaque reduction RSV neutralization titer < 8.0 log(2).

        EXCLUSION CRITERIA:

          1. Subject who was previously challenged with RSV A2.

          2. Female subject who is pregnant or lactating OR planning to become pregnant from 30
             days prior to inoculation through 30 days after inoculation.

          3. Presence of self-reported or medically documented significant medical condition(s)
             including but not limited to:

             -Respiratory disease (e.g., chronic obstructive pulmonary disease, emphysema,
             rhinitis, sinusitis) in adulthood, and additionally:

             --A history of asthma within the past 5 years, or a current diagnosis of asthma or
             reactive airway disease associated with

             exercise, seasonal hay fever or allergic rhinitis

             --Presence of any febrile illness or symptoms suggestive of a respiratory infection
             within 2 weeks prior to inoculation.

               -  Any significant abnormality of the nose or nasopharynx, including recurrent
                  epistaxis within 90 days prior to viral inoculation or nasal or sinus surgery
                  within 180 days prior to viral inoculation.

               -  Chronic cardiovascular disease (e.g., congestive heart failure, cardiomyopathy,
                  ischemic heart disease).

               -  Chronic neurological or neurodevelopmental conditions (e.g., cerebral palsy,
                  epilepsy, stroke, seizures).

               -  Ongoing malignancy.

               -  Chronic medical condition requiring close medical follow-up or hospitalization
                  during the past 5 years (e.g., diabetes mellitus, renal dysfunction,
                  hemoglobinopathy, autoimmune disease).

               -  An immunodeficiency.

          4. Use of systemic corticosteroids exceeding 10 mg/day of prednisone equivalent and nasal
             steroid preparations or immunosuppressive drugs within 30 days before inoculation and
             within 60 days after. Low dose topical steroid preparations used for a discrete period
             of time are permitted.

          5. Inhaled bronchodilator or inhaled steroid use within the last 360 days or use after
             upper respiratory tract infections.

          6. Behavioral or cognitive impairment or psychiatric disease that in the opinion of the
             investigator affects the ability of the subject to understand and cooperate with the
             study protocol.

          7. Complete blood count (CBC), aspartate aminotransferase (AST), alanine aminotransferase
             (ALT), creatinine values or other screening labs or tests (e.g. electrocardiogram
             (EKG), chest x-ray (CXR)) are outside of the NIH Department of Laboratory Medicine
             normal reference range and deemed clinically significant by the PI.

          8. Positive FDA-approved HIV test obtained during screening procedures.

          9. Positive serology for hepatitis C virus obtained during screening period.

         10. Presence of hepatitis B surface antigen obtained during screening period.

         11. A smoker of tobacco products or a routine marijuana smoker currently or in the past
             year.

         12. Current alcohol abuse or addiction.

         13. Current illicit drug abuse or addiction.

         14. Receipt of a licensed vaccine within 30 days prior to RSV A2 inoculation and planned
             vaccination within 60 days after inoculation..

         15. Receipt of blood or blood-derived products (including immunoglobulin) within 180 days
             prior to viral inoculation. Receipt of packed red blood cells given for an emergent
             indication in an otherwise healthy person, and not required as ongoing treatment, is
             not exclusionary.

         16. Receipt of an investigational agent or vaccine within 90 days prior to scheduled RSV
             A2 inoculation and planned receipt within 60 days after inoculation.

         17. A body mass index (BMI) less than or equal to 18.5 or greater than or equal to 37.0.

         18. A medical, occupational, or family problem that would preclude the participant from
             complying with all study requirements.

         19. Shares household, works closely with, or has routine contact with a child (children) <
             5 years of age or with immunocompromised individual(s), adult(s) with significant
             cardiopulmonary disease or asthma, institutionalized persons or persons with
             functional disability, or any other individual that, in the judgment of the PI, might
             be at increased risk for complications if exposed to RSV.

         20. Deprived of freedom by an administrative or court order or in an emergency setting.

         21. Any condition that in the opinion of the PI would jeopardize the safety or rights of a
             person participating in the trial or would render the person unable to comply with the
             protocol.