Evaluating the Safety and Immune Response to a Single Dose of a Respiratory Syncytial Virus (RSV) Vaccine in 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.
The purpose of this study is to evaluate the safety and immunogenicity of a single dose of a
RSV vaccine in healthy children. Study researchers will first evaluate the vaccine in healthy
RSV-seropositive children, then evaluate the vaccine in healthy RSV-seronegative infants and
children, followed by younger infants not screened for RSV serostatus.

This study will first enroll healthy RSV-seropositive children ages 12 to 59 months (Group
1). At study entry, participants will undergo a medical history review, physical examination,
blood collection, and a nasal wash procedure. Participants will be randomly assigned to
receive either the RSV vaccine or placebo vaccine, administered as nose drops. Subjects 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 where no study visit is scheduled, study researchers will contact participants'
parents or guardians for medical follow-up.

Study researchers will evaluate the study data of participants in Group 1 before enrolling
participants in Group 2, and study data from Group 2 will be reviewed before enrolling
participants in Group 3. Finally, study data from Group 3 will be reviewed before enrolling
participants in Group 4. Participants in Groups 2 and 3 will include healthy RSV-seronegative
infants and children ages 6 to 24 months. Participants in Group 4 will include healthy
infants, ages 4 to 6 months, who have not been screened for RSV serostatus.

Participants in Groups 2, 3, and 4 will be randomly assigned to receive either the RSV
vaccine or placebo vaccine, administered as nose drops. Subjects will be actively monitored
for 56 days following administration of vaccine or placebo; monitoring will include medical
history reviews, clinical assessments, and at some visits, nasal washes. On the days where 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.

For participants in Groups 2, 3, and 4, from November through March following each
participant's vaccination visit, parents or guardians will monitor participants for
RSV-associated illnesses and report these 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. Participants in Groups 3 and 4
will have the option to take part in additional monitoring for a second RSV season.

Inclusion Criteria for Seropositive Children:

- Healthy children at least 12 but less than 60 months of age, whose parent/guardian
understands and signs the study informed consent and who agrees to vaccine
administration following a detailed explanation of the study

- Seropositive for RSV as defined by serum RSV neutralizing antibody titer equal to or
greater than 1:40. If a child at least 12 but less than 60 months of age is determined
to be RSV seropositive prior to Day 56, s/he does not need an additional screening
serum specimen, but a pre-inoculation serum specimen must be obtained.

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

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

Exclusion Criteria for Seropositive Children:

- Known or suspected impairment of immunological functions, including maternal history
of positive HIV test, receiving immunosuppressive therapy including systemic
corticosteroids, or bone marrow/solid organ transplant recipients (topical steroids,
topical antibiotics, and topical antifungal medications are acceptable)

- 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 immunocompromised individual or infants less
than 6 months of age, other than a study participant

- 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.

Inclusion Criteria for Seronegative Infants and Children:

- Healthy children at least 6 but less than 25 months of age whose parents/guardians can
understand and sign the informed consent and who 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 not more than 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 is expected to be available for the duration of the study

Exclusion Criteria for Seronegative Infants and Children:

- Known or suspected impairment of immunological functions, including maternal history
of positive HIV test, receiving immunosuppressive therapy including systemic
corticosteroids, or 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 immunocompromised individual or infants less
than 6 months of age

- Attends daycare 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.

Inclusion Criteria for Infants (Group 4):

- Healthy infants 4 to 6 months of age whose parents/guardians can understand and sign
the informed consent and who agree to vaccine administration following detailed
explanation of the study.

- Subject's history has been reviewed and subject 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.

- Subject is expected to be available for the duration of the study.

Exclusion Criteria for Infants (Group 4):

- Known or suspected impairment of immunological functions, including maternal history
of positive HIV test, receiving immunosuppressive therapy including systemic
corticosteroids or 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.
Subjects with clinically insignificant cardiac abnormalities requiring no treatment
may be enrolled.

- Member of a household that includes an immunocompromised individual or infants less
than 4 months of age.

- Attends daycare with infants less than 4 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.

Temporary Exclusion Criteria for Seropositive Children, Seronegative Children, and Infants:

The following are temporary or self-limiting conditions, and once resolved, the subject may
be enrolled, if otherwise eligible. If the period of temporary exclusion is greater than 42
days, seronegative children will need to be rescreened for levels of RSV neutralizing
antibody.

- 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

- Subject has received any killed vaccine or live attenuated rotavirus vaccine within 14
days prior to inoculation, any other live vaccine within 28 days prior to inoculation,
or gamma globulin (or other antibody products) within the past 3 months prior to
inoculation.

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

- Has received antibiotics or systemic or nasal steroid therapy for acute illness within
the previous 3 days prior to vaccination (steroid skin creams or lotions and topical
antibiotics or antifungal preparations are permitted)

- Has received salicylate (aspirin) or salicylate-containing products within 28 days
prior to inoculation

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

Inclusion Criteria for Second Year of RSV Surveillance

- Those children who have completed the initial study and whose parents/guardians can
understand and sign the informed consent.

- Subject is expected to be available during the second year of RSV surveillance.

Exclusion Criteria for Second Year of RSV Surveillance

- Currently enrolled in another RSV study.