Safety and Immune Response to a Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccine in RSV-Seronegative Infants and Children
Safety and Immune Response to a Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccine in RSV-Seronegative Infants and Children
Respiratory syncytial virus (RSV) is a common cause of illness in infants and children around
 the world. This study will evaluate the safety and immune response to an RSV vaccine in
 RSV-seronegative infants and children.

 This study is a companion study to IMPAACT 2000.
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