Evaluating the Safety and Immune Response to a Respiratory Syncytial Virus (RSV) Vaccine in Adults, RSV-Seropositive Children, and RSV-Seronegative Infants and Children

The purpose of this study is to evaluate the safety and immune response of the RSV MEDI
ΔM2-2 vaccine in the four groups of participants. The study vaccine will be evaluated in
adults, in RSV-seropositive children, and in a dose-ranging study in two groups of
RSV-seronegative infants and children.

Inclusion Criteria for Adults:

- Adult males and nonpregnant, non-nursing females 18 to 49 years old

- In good health without significant medical illness, physical examination findings, or
significant laboratory abnormalities in urinalysis, complete blood count (CBC),
alanine aminotransferase (ALT), or creatinine, as determined by a study physician,
physician assistant, or nurse practitioner

- Available for the duration of the study

- Willing to participate in the study as evidenced by signing the informed consent
document

- Female participants of childbearing potential must have negative urine pregnancy
tests and must agree to use effective birth control methods (e.g., birth control
pills, diaphragm and foam, condoms with spermicide, Depo-Provera) until 28 days after
vaccination

Exclusion Criteria for Adults:

- Pregnant, as determined by a positive urine human chorionic gonadotropin (beta-HCG)
test

- Breastfeeding

- Females of childbearing potential who are unwilling to practice effective birth
control

- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic,
rheumatologic, autoimmune, or renal disease by history, physical examination, and/or
laboratory studies, including urinalysis

- Behavioral, cognitive, or psychiatric disease that, in the opinion of the
investigator, affects the ability of the person to understand and cooperate with the
study protocol

- Other condition that, in the opinion of the investigator, would jeopardize the safety
or rights of a participant in the study or would render the person unable to comply
with the protocol

- Has had medical, occupational, or family problems as a result of alcohol or illicit
drug use during the 12 months prior to study entry

- History of a severe allergic reaction or anaphylaxis

- History of splenectomy

- Current diagnosis of asthma within the 2 years prior to study entry

- Positive enzyme-linked immunosorbent assay (ELISA) and confirmatory Western blot
tests for HIV-1

- Positive ELISA and confirmatory immunoblot tests for hepatitis C virus (HCV)

- Positive ELISA hepatitis B surface antigen (HBsAg)

- Abnormal urinalysis/urine dip

- Known immunodeficiency syndrome

- Receipt of blood products (including immunoglobulin) within the 3 months prior to
study entry

- Current smoker unwilling to stop smoking for the duration of the study

- Previous enrollment in an RSV vaccine study

- Known hypersensitivity to any vaccine component

- Has professional and/or personal responsibilities that involve caring for children
younger than 59 months of age or for immunosuppressed individuals

- Systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater
than 90 mm Hg

- Body mass index (BMI) greater than 35

Inclusion Criteria for Seropositive Children:

- Healthy children 12 to 59 months of age, whose parent/guardian understands and signs
the study informed consent and agrees to vaccine administration following a detailed
explanation of the study

- Seropositive for RSV, defined by serum RSV neutralizing antibody titer greater than
1:40

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

- 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

- Previous serious vaccine-associated adverse event (AE) or anaphylactic reaction

- Known hypersensitivity to any vaccine component

- Lung or heart disease, including any wheezing event or reactive airway disease.
People with clinically insignificant cardiac abnormalities requiring no treatment may
be enrolled. People 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
younger than 6 months of age, other than a study participant

- Attends day care with infants younger 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 6 to 24 months of age whose parents/guardians can understand and
sign the informed consent and agree to vaccine administration following detailed
explanation of the study

- Seronegative for RSV antibody, defined by serum RSV neutralizing antibody titer less
than 1:40 determined within 30 days prior to inoculation

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

- 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 (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

- 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.
People with clinically insignificant cardiac abnormalities requiring no treatment may
be enrolled. People 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
younger 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. 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 All Participants:

The following are temporary or self-limiting conditions and, once resolved, the person may
be enrolled, if otherwise eligible. If the period of temporary exclusion is more than 56
days for adults or more than 30 days for RSV-seronegative children, the person will need
to be rescreened. If the period of temporary exclusion is more than 56 days for
RSV-seropositive children, a pre-inoculation serum antibody will need to be collected.

- Fever (adult oral temperature of greater than or equal to 100.4°F [38°C] or pediatric
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

- Has received any killed vaccine or live attenuated rotavirus vaccine within the 2
weeks prior to study entry, any other live vaccine within the 4 weeks prior to study
entry, or gamma globulin (or other antibody products) within the 3 months prior to
study entry

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

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

- Infant or child participant has received salicylate (aspirin) or
salicylate-containing products within the 1 month prior to study entry

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