Evaluating the Safety and Immune Response to a Single Dose of a 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 around the world. RSV illness can range from mild
upper respiratory tract illness (URI) to severe LRI, including bronchiolitis and pneumonia.
This study will evaluate the safety and immunogenicity of an RSV vaccine in healthy
RSV-naïve children.

At study entry, participants will undergo a medical history review, physical examination,
blood collection, and a nasal wash. Participants will be randomly assigned to receive the
RSV vaccine or placebo at a 2:1 ratio, to be administered as nose drops. Participants will
be actively monitored for 28 days following administration of vaccine or placebo; monitoring
will include medical history reviews, clinical assessments, and at some visits, nasal
washes. On the days when no study visit is scheduled, study researchers will contact
participants' parents or guardians for medical follow-up. At a study visit on Day 56,
participants will undergo a medical history review, blood collection, and a nasal wash
procedure.

From November through March following each participant's study participation, parents or
guardians will report respiratory and/or febrile illnesses on a weekly basis via telephone
calls to study researchers. Participants may have additional study visits that may include
blood collection and/or nasal wash procedures during this follow-up period.

This protocol is a companion study to CIR 285; a study being conducted by the Center for
Immunization Research (CIR, Johns Hopkins, Baltimore), and the Laboratory of Infectious
Diseases (NIAID, Bethesda). The protocols have identical primary and secondary objectives;
immunization schedules; evaluation assays and schedules; safety monitoring and reporting.
The protocols will vary slightly in site selection requirements, eligibility requirements
and site monitoring. These are all operational issues modified to account for the IMPAACT
sites' operations and infrastructure.

Inclusion Criteria:

- Parents/guardians who demonstrate their understanding of the study (by taking a
multiple choice questionnaire), sign the informed consent, and agree 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 enrollment/immunization

- Participant's history has been reviewed and participant has undergone a physical
examination indicating that s/he is in good health

- In the view of the site investigator, the participant has received routine
immunizations appropriate for their age

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

- For children born to HIV-infected women: two negative polymerase chain reaction (PCR)
tests with one collected when greater than 1 month of age and one collected when
greater than 4 months old, and no positive HIV PCR test; or two negative HIV antibody
tests

Exclusion Criteria:

- Known or suspected impairment of immunological functions or HIV infection

- Receipt of immunosuppressive therapy including systemic corticosteroids within 30
days of study entry. NOTE: Topical steroids, topical antibiotic, and topical
antifungal medications are acceptable within 24 hours of enrollment. May be
reassessed after symptoms have resolved.

- Bone marrow/solid organ transplant recipients

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

- Previous immunization with an RSV vaccine or previous receipt of or planned
administration of any anti-RSV antibody product

- Previous serious vaccine-associated AE or anaphylactic reaction

- Known hypersensitivity to any vaccine component

- Lung or heart disease, including any wheezing event or reactive airway disease.
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 also be enrolled.

- Member of a household that includes an infant less than 6 months of age

- Member of a household that contains an immunocompromised individual (including, but
not limited to: those with HIV-related immunodeficiency, defined as CD4 less than
300, or less than 15% if less than 5 years of age, measured within the previous 6
months; or any household members who have received chemotherapy within the last 12
months). Verbal report is sufficient documentation if the parent/guardian is
confident of history.

- 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. Children
who attend facilities that separate children by age and minimize opportunities for
transmission of virus through direct physical or aerosol contact are acceptable.

- Fever (rectal temperature of greater than or equal to 100.4°F [38°C]), or upper
respiratory illness (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, or is scheduled to
receive any immunization in the 28 days after enrollment

- Receipt of another investigational vaccine or investigational drug within 28 days of
receiving this investigational RSV vaccine

- Participant has received antibiotics or systemic or nasal steroid therapy or other
prescription medications for acute illness within 3 days of study entry. 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

- Infants born at less than 37 weeks gestation and less than 1 year of age