Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase I Placebo-Controlled Study of the Infectivity, Safety and Immunogenicity of a Single Dose of a Recombinant Live-attenuated Respiratory Syncytial Virus Vaccine, LID cp ΔM2-2, Lot RSV#009B, Delivered as Nose Drops to RSV-Seronegative Infants and Children 6 to 24 Months of Age
Brief Summary: The purpose of this study is to evaluate the safety, infectivity, and immunogenicity of a single dose of a recombinant live-attenuated respiratory syncytial virus (RSV) vaccine in RSV-seronegative infants and children 6 to 24 months of age.

This study is a companion study to IMPAACT 2012.


Options:
A: Adult Inclusion Criteria:

* In good health
* Available for the duration of the trial
* Available for post-inoculation telephone contact
* For females, must agree to use effective birth control methods for the duration of the study

Seropositive Children Inclusion Criteria:

* In good health
* Seropositive for HPIV1
* Available for the duration of the study

Seronegative Infants and Children Inclusion Criteria:

* In good health
* Seronegative for HPIV1 antibody
* Available for the duration of the study

Adult Exclusion Criteria:

* Neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease
* Condition, in the opinion of the investigator, that will not allow the participant to comply with the protocol
* Alcohol or drug abuse
* History of anaphylaxis
* History of splenectomy
* Diagnosis of asthma within 2 years of study entry
* HIV-infected
* Hepatitis C infection
* Hepatitis B infection
* Abnormal urinalysis
* Known immunodeficiency syndrome
* Current use of nasal or systemic steroid medications
* Receipt of blood products within 3 months of study entry
* Current smoker unwilling to stop smoking for the duration of the study. The decision to exclude a potential subject is made by the investigator based upon the potential subject's medical history and physical examination.
* Participation in another investigational vaccine or drug trial within 30 days of receiving the investigational vaccine
* Receipt of live vaccine within 4 weeks or a killed vaccine within 2 weeks or immune globin within 3 months prior to receiving the investigational vaccine
* Previous immunization with an HPIV1 vaccine
* Known hypersensitivity to any vaccine component
* Participants whose profession and/or personal responsibilities involve caring for children less than 6 months of age or for immunosuppressed individuals
* Persistent systolic blood pressure more than 140 mm Hg or diastolic pressure more than 90 mm Hg
* Body mass index (BMI) more than 35
* Pregnant or breastfeeding

Seropositive and Seronegative Infants and Children Exclusion Criteria:

* Known or suspected impairment of immunological functions as determined by the investigator
* Major congenital malformations, including congenital cleft palate, cytogenetic abnormalities, or serious chronic disorders
* Previous immunization with HPIV1 vaccine
* Current use of nasal or systemic steroid medications
* Previous serious vaccine-associated adverse event or anaphylactic reaction
* Known hypersensitivity to any vaccine component
* Lung or heart disease, including reactive airway disease as determined by the investigator
* Member of household that includes an immunocompromised individual or infant less than 6 months of age
* Attends day care with infants less than 6 months of age or immunosuppressed individuals. More information about this criterion can be found in the protocol.
* Participation in another investigational vaccine or drug trial within 30 days of receiving the investigational vaccine or while study is occurring
B: Inclusion Criteria:

* Greater than or equal to 6 months (greater than or equal to 180 days) of age at the time of screening and less than 25 months (less than 750 days) of age
* Participant is in good health based on review of the medical record, history, and physical examination, without evidence of chronic disease
* Parents/guardians are willing and able to provide written informed consent
* Seronegative for RSV antibody, defined as a serum RSV-neutralizing antibody titer less than 1:40 at screening from a sample collected no more than 42 days prior to inoculation
* Is growing at a normal velocity for age as demonstrated on a standard growth chart AND

  * If less than 1 year of age: has a current height and weight above the 5th percentile
  * If 1 year of age or older: has a current height and weight above the 3rd percentile for age
* Participant has received routine immunizations appropriate for age (as per Center for Disease Control Advisory Committee on Immunization Practices \[ACIP\])
* Participant is expected to be available for the duration of the study

Exclusion Criteria:

* Known or suspected HIV infection or impairment of immunological functions
* Receipt of immunosuppressive therapy, including any systemic, including either nasal or inhaled, corticosteroids within 28 days of enrollment. Note: Cutaneous (topical) steroid treatment is not an exclusion.
* Bone marrow/solid organ transplant recipient
* Major congenital malformations (such as congenital cleft palate) or cytogenetic abnormalities
* Previous receipt of a licensed or investigational RSV vaccine or receipt of placebo in any IMPAACT RSV study or previous receipt of or planned administration of any anti-RSV product (such as ribavirin or RSV Ig or RSV mAb)
* Previous anaphylactic reaction
* Previous vaccine-associated adverse reaction that was Grade 3 or above
* Known hypersensitivity to any study product component
* Heart disease. Note: Participants with cardiac abnormalities documented to be clinically insignificant and requiring no treatment may be enrolled
* Lung disease, including any history of reactive airway disease or medically documented wheezing
* Member of a household that contains, or will contain, an infant who is less than 6 months of age at the enrollment date through Day 28
* Member of a household that contains another child who is, or is scheduled to be, enrolled in CIR 311, 312 or 313 AND there has been or will be an overlap in residency during that other child's participation in the study's Acute Phase (Days 0 to 28)
* Member of a household that contains an immunocompromised individual, including but not limited to:

  * a person who is HIV infected
  * a person who has received chemotherapy within the 12 months prior to enrollment
  * a person receiving immunosuppressant agents
  * a person living with a solid organ or bone marrow transplant
* Attends a daycare facility and shares a room with infants less than 6 months of age, and parent/guardian is unable or unwilling to suspend daycare for 28 days following inoculation
* Any of the following events at the time of enrollment:

  * fever (temporal or rectal temperature of greater than or equal to 100.4°F), or
  * upper respiratory signs or symptoms (rhinorrhea, cough, or pharyngitis) or
  * nasal congestion significant enough to interfere with successful inoculation, or
  * otitis media
* Receipt of the following prior to enrollment:

  * any killed vaccine or live-attenuated rotavirus vaccine within the 14 days prior, or
  * any live vaccine, other than rotavirus vaccine, within the 28 days prior, or
  * another investigational vaccine or investigational drug within 28 days prior
* Scheduled administration of the following after planned inoculation:

  * killed vaccine or live-attenuated rotavirus vaccine within the 14 days after, or
  * any live vaccine other than rotavirus in the 28 days after, or
  * another investigational vaccine or investigational drug in the 56 days after
* Receipt of immunoglobulin, any antibody products, or any blood products within the past 6 months
* Receipt of any of the following medications within 3 days of study enrollment:

  * systemic antibacterial, antiviral, antifungal, anti-parasitic, or antituberculous agents, whether for treatment or prophylaxis, or
  * intranasal medications, or
  * other prescription medication except as listed below
* Receipt of salicylate (aspirin) or salicylate-containing products within the past 28 days
* Born at less than 34 weeks gestation
* Born at less than 37 weeks gestation and less than 1 year of age at the time of enrollment
* Suspected or documented developmental disorder, delay, or other developmental problem
* Previous receipt of supplemental oxygen therapy in a home setting
C: 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.
D: Inclusion Criteria:

* Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol
* Written informed consent obtained from the subject prior to performing any study specific procedure
* A male or female between, and including, 18 and 45 years of age at the time of first vaccination
* Healthy subjects as established by medical history and clinical examination before entering into the study
* Female subjects of non-childbearing potential may be enrolled in the study
* Female subjects of childbearing potential may be enrolled in the study, if the subject:

  * has practiced adequate contraception for 30 days prior to vaccination, and
  * has a negative pregnancy test on the day of vaccina-tion, and
  * has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series

Exclusion Criteria:

* Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product
* Use of any investigational or non-registered product other than the study vaccines during the period starting 30 days before the first dose of study vaccines, or planned use during the study period
* Chronic administration of immunosuppressants or other immune-modifying drugs within 6 months prior to study vaccination, or planned administration during the study period
* Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose and ending 30 days after the last dose of vaccine administration, with the exception of any licensed influenza vaccine which may be administered ≥ 15 days before the first dose and ≥ 15 days after the last dose of study vaccine
* Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first dose of study vaccines or planned administration during the study period
* Blood donation within 4 months prior to study entry or planned blood donation at any time during the study
* Previous vaccination against RSV
* Previous vaccination with a recombinant simian or human adenoviral vaccine
* Previous Bexsero or other vaccination against Neisseria meningitidis serogroup B
* History of or current autoimmune disease
* Family history of congenital or hereditary immunodefi-ciency
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccines.
* History of any neurological disorders or seizures
* History of transient thrombocytopenia or neurological complications following any prior vaccination
* Hypersensitivity to latex
* Hypersensitivity to Bexsero's active substances or to any of its excipients
* Allergic reaction to kanamycin
* Any medical condition that in the judgment of the investi-gator would make intramuscular injection unsafe
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination
* Acute disease and/or fever at the time of enrolment
* Acute or chronic, clinically significant pulmonary, cardio-vascular, hepatic or renal functional abnormality, as de-termined by physical examination or laboratory screening tests
* Malignancy within previous 5 years or lymphoproliferative disorders
* Any clinically significant or any ≥ Grade 2 haematological laboratory abnormality
* Body mass index \> 40 kg/m2
* Current alcohol and/or drug abuse
* Pregnant or lactating female
* Any other condition that the investigator judges may interfere with study procedures or findings
* Planned move to a location that will prohibit participating in the trial until study end

Answer: B