Safety and Immune Response to a Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccine in RSV-Seronegative Infants and Children

RSV is the most common viral cause of serious acute lower respiratory illness (LRI) in
infants and children under 5 years of age in the world. RSV illness can range from mild
upper respiratory tract illness (URI) to severe LRI, including bronchiolitis and pneumonia.
Severe RSV disease in infancy may also predispose children to develop reactive airway
disease during childhood. The purpose of this study is to evaluate the safety and
immunogenicity of an RSV vaccine (RSV LID ΔM2-2) in RSV-seronegative infants and children at
least 6 months and through 24 months of age.

To determine study eligibility, the screening process will include a blood collection. At
study entry, eligible participants will be randomly assigned to receive one dose of either
the RSV vaccine or placebo, which will be delivered as nose drops. Participants will also
undergo a review of medical history, clinical assessment, and a nasal wash. They will then
receive their assigned vaccine and will remain under observation for monitoring for 30
minutes after receiving the vaccine. Additional study visits will occur at Days 3, 5, 7, 10,
12, 14, 17, 19, 21, 28, and 56. These visits will include clinical assessments and nasal
washes; on Day 56, a blood collection will also occur. On days where no study visit is
scheduled (through Day 27), participants' parents or guardians will report participants'
temperatures and signs of illness to researchers by e-mail or phone.

In October following vaccination, participants may have a pre-RSV season blood collection
visit. During RSV season, November through March following vaccination, researchers will
contact participants' parents or guardians on a weekly basis for follow-up monitoring.
During this time frame, participants seen by a medical provider for fever, respiratory
illness, or otitis media will have a study visit, which will include a nasal wash and
clinical assessment. In April following vaccination, participants will undergo a final blood
collection.

Inclusion Criteria:

- Participant is at least 6 months but less than 25 months of age at the time of
inoculation

- Parent or guardian who demonstrates their understanding of the study, signs the
informed consent, and agrees to vaccine administration following detailed explanation
of the study

- Seronegative for RSV antibody, defined as a serum RSV neutralizing antibody titer
less than 1:40 as determined within 42 days prior to inoculation

- Participant's history has been reviewed and participant has undergone a physical
examination indicating that s/he is in good health. Permitted concomitant medications
include nutritional supplements, medications for gastroesophageal reflux, eye drops,
and topical medications, including topical steroids, topical antibiotics, and topical
antifungal agents.

- Participant has received routine immunizations appropriate for age, administered:

1. at least 2 weeks prior to study vaccine inoculation (inactivated and subunit
vaccines and rotavirus vaccine) OR

2. at least 4 weeks prior to study vaccine inoculation (all other live vaccines)

- Participant is expected to be available for the duration of the study

Exclusion Criteria:

- Known or suspected impairment of immunological functions, including maternal history
of positive HIV test

- Receipt of immunosuppressive therapy including systemic corticosteroids within the
past 30 days. NOTE: Topical steroids, topical antibiotics, and topical antifungal
medications are acceptable.

- Bone marrow/solid organ transplant recipient

- Major congenital malformations, including congenital cleft palate, cytogenetic
abnormalities, or serious chronic disorders

- Previous immunization with an RSV vaccine

- Previous serious vaccine-associated AE or any anaphylactic reaction

- Known hypersensitivity to any vaccine component

- Lung or heart disease, including any wheezing event or reactive airway disease. NOTE:
Participants with clinically insignificant cardiac abnormalities requiring no
treatment may be enrolled. Participants who had one episode of wheezing or received
bronchodilator therapy for a single episode of illness in the first year of life but
who have not had any additional wheezing episodes or bronchodilator therapy for at
least 12 months may be enrolled.

- Member of a household that contains an immunocompromised individual

- Member of a household that contains infants less than 6 months of age

- Attends day care with infants less than 6 months of age, and whose parent/guardian is
unable or unwilling to suspend daycare for 14 days following immunization. NOTE:
Children who attend facilities that separate children by age and minimize
opportunities for transmission of virus through direct physical or aerosol contact
are acceptable.

Temporary Exclusion Criteria:

The following are temporary or self-limiting conditions. Once resolved, the participant
may be enrolled, if otherwise eligible, and if the period of temporary exclusion has been
less than 42 days from screening. Otherwise, the participant will need to be rescreened.

- Participant has a rectal temperature of greater than or equal to 100.4°F on the day
of planned vaccination, or URI (rhinorrhea, cough, or pharyngitis) or nasal
congestion significant enough to interfere with successful vaccination, or otitis
media

- Participant has received any killed vaccine or live attenuated rotavirus vaccine
within the last 2 weeks, any other live vaccine within the last 4 weeks, or gamma
globulin (or other antibody products) within the past 3 months

- Receipt of another investigational vaccine or investigational drug within the prior
28 days of receiving the study inoculation

- Participant has received antibiotics or systemic or nasal steroid therapy for acute
illness within the previous 3 days prior to vaccination. NOTE: Permitted concomitant
medications include nutritional supplements, medications for gastroesophageal reflux,
eye drops, and topical medications, including (but not limited to) topical steroids,
topical antibiotics, and topical antifungal agents.

- Participant has received salicylate (aspirin) or salicylate-containing products
within the past month

- Participant born at less than 37 weeks gestation and is currently less than 1 year of
age