Safety of and Immune Response to a Cow/Human Parainfluenza Virus Vaccine (rB/HPIV3) in Healthy Infants, Children, and Adults

HPIV type 3 (HPIV3) ranks second only to respiratory syncytial virus as the most common
cause of bronchiolitis and pneumonia in infants less than 6 months of age. HPIV3 can cause
severe disease in the first 2 years of life and is responsible for 11% of hospitalizations
for respiratory diseases in children. This study will evaluate the safety and immunogenicity
of a live, chimeric bovine/human, attenuated intranasal HPIV3 vaccine, rB/HPIV3. This
vaccine combines modified human HPIV3 with a related, modified cow virus, bovine
parainfluenza type 3 virus (BPIV3). Vaccinations will be given as nose drops to healthy
adults, children seropositive for HPIV3, and infants and children seronegative for HPIV3.

There are four groups in this study. Group 1 will consist of adults who will receive the
higher dose of rB/HPIV3. Group 2 will consist of seropositive children who will be randomly
assigned to receive the higher dose of rB/HPIV3 or placebo. Group 2 will not begin
enrollment until the completion of Group 1 safety data review. Participants of both Groups 1
and 2 will be monitored for 10 days post vaccination for respiratory illness and for fever
by self-reported temperature logs; these participants will be followed for a maximum of 28
days. Blood collection will occur at study entry and on Day 28; additional blood collection
may occur up to 28 days prior to vaccination. Clinical assessments and nasal washes will
occur at study entry and selected study visits. Group 1 participants will be contacted by
phone on Day 180; Group 2 participants' parents or guardians will be contacted by phone on
Days 1, 2, 8, 9, 11, and 180; study staff will ask about any illnesses or adverse events
that may have occurred.

Groups 3 and 4 will consist of seronegative infants and children. Group 3 will not begin
enrollment until the completion of Group 2 safety data review. Children in Group 3 will be
randomly assigned to receive the lower dose of rB/HPIV3 or placebo. Group 4 will not begin
enrollment until the completion of Group 3 safety data review. Children in Group 4 will be
randomly assigned to receive the higher dose of rB/HPIV3 or placebo. Participants of both
Groups 3 and 4 will be monitored closely for 28 days postvaccination for respiratory illness
and for fever by self-reported temperature logs; these participants will be followed for a
maximum of 56 days. Blood collection will occur at study entry and on Day 56. Clinical
assessments and nasal washes will occur at study entry and most study visits. Participants'
parents or guardians will be contacted by phone periodically post vaccination; study staff
will ask about any illnesses or adverse events they may have observed in their infants or
children.