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 6 to 24 Months of Age
Brief Summary: The purpose of this study was to evaluate the safety, infectivity, and immunogenicity of a single intranasal dose of a recombinant live-attenuated respiratory syncytial virus (RSV) vaccine in RSV-seronegative infants 6 to 24 months of age.

This study was a companion study to CIR 312.


Options:
A: 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.
* Non-pregnant female between, and including, 18 and 45 years of age at the time of 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 vaccination and
  * has agreed to continue adequate contraception during the entire study period.

Exclusion Criteria:

* Use of any investigational or non-registered product other than the study vaccine within 30 days prior to study vaccination, or planned use during the study period.
* 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.
* Chronic administration of immunosuppressants or other immune-modifying drugs, as well as administration of long-acting immune-modifying drugs during the period starting 6 months prior to study vaccination, or planned administration during the study period. Inhaled and topical steroids are allowed.
* Administration of immunoglobulins and/or any blood products during the period starting 3 months before 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 and ending 30 days after the study vaccination, with the exception of any licensed influenza vaccine which may be administered ≥ 15 days before or after study vaccination.
* Previous experimental vaccination against RSV.
* Family history of congenital or hereditary immunodeficiency.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* History of or current auto-immune disease.
* Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality as determined by physical examination and/or Medical History.
* Lymphoproliferative disorder or malignancy within previous 5 years.
* History of hypersensitivity after a previous dose of any tetanus, diphtheria, or pertussis vaccine or to any component of Boostrix.
* History of encephalopathy of unknown aetiology occurring within 7 days following a previous vaccination with pertussis-containing vaccine.
* History of any neurological disorders or seizures.
* History of transient thrombocytopenia or neurological complications following a previous vaccination against diphtheria and/or tetanus.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccines.
* Hypersensitivity to latex.
* Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
* Current chronic alcohol consumption and/or drug abuse.
* Acute disease and/or fever at the time of enrolment.
* Body mass index (BMI) \> 40 kg/m2.
* Pregnant or lactating female.
* Planned move to a location that will prohibit participating in the trial until study end.
* Any other condition that the investigator judges may interfere with study procedures.
B: Inclusion Criteria:

* Age ≥ 60 years at the time of screening.
* Medically stable such that, according to the judgment of the investigator, hospitalization within the study period is not anticipated and the subject appears likely to be able to remain in follow-up through the end of protocol-specified follow-up.
* (Season 2): Subject received MEDI7510 and IIV in the Northern Hemisphere in Season 1.

Exclusion Criteria:

* History of allergy to any component of the vaccine.
* Receipt of seasonal influenza vaccine within 6 months prior to Season 1 dosing.
* History of allergy to or intolerance of IIV.
* Pregnancy or potential to become pregnant during the study. Females who (1) have had a menstrual period within the 12 months prior to study enrollment or (2) are undergoing any fertility treatment or who plan to undergo fertility treatments during the study period are excluded.
* History of Guillain-Barré syndrome.
* Previous vaccination against RSV.
* History of allergy to eggs in adulthood.
* History of or current autoimmune disorder, with the exception of stable, treated hypothyroidism caused by autoimmune thyroiditis, which is acceptable.
* Immunosuppression caused by disease, including human immunodeficiency virus infection (assessed by history), or medications. Any receipt of oral or intravenous glucocorticoid therapy within 30 days prior to enrollment or planned dosing within the follow-up period would disqualify. Topical, intranasal, inhaled, or intra-articular corticosteroids do not disqualify. Expected need for immunosuppressive medications during the follow-up period would disqualify.
* History of cancer within preceding 5 years other than treated non-melanoma skin cancer, locally-treated cervical cancer or in situ carcinoma of the breast.
* Receipt of any non-study vaccine within 28 days prior to study dosing or expected receipt of non-study vaccine prior to the Day 29 visit in Season 1.
* Receipt of any investigational product (IP) in the 90 days prior to randomization or expected receipt of IP during the period of study follow-up.
* Receipt of immunoglobulins or blood products within 4 months of study dosing (120 days) or expected receipt of immunoglobulins or blood products during the period of study follow-up.
* Current bleeding or clotting disorder including use of anticoagulants other than drugs with anti-platelet activity (such as nonsteroidal anti-inflammatory drugs, clopidogrel, ticagrelor or aspirin).
* History of alcohol or drug abuse or psychiatric disorder that, in the opinion of the investigator, would affect the subject's safety or compliance with study.
* (Season 2): Related Grade 3 or 4 adverse event (AE) including Grade 3 or 4 local reaction to either MEDI7510 or IIV, any adverse event of special interest (AESI) for an adjuvanted vaccine, or any related serious adverse event (SAE).
C: Inclusion Criteria:

* Greater than or equal to 6 months (defined as greater than or equal to 180 days) of age at the time of screening and less than 25 months (defined as less than 750 days) of age.
* Good health based on review of the medical record, history, and physical examination, without evidence of chronic disease.
* Parents/guardians willing and able to provide written informed consent as described in the protocol.
* 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. Note: results from specimens collected during screening for IMPAACT 2011 were acceptable as long as within the 42-day window.
* Growing at a normal velocity for age (as demonstrated on a standard growth chart) AND

  * If less than 1 year of age: current height and weight above the 5th percentile.
  * If 1 year of age or older: current height and weight above the 3rd percentile for age.
* Received routine immunizations appropriate for age (as per national Center for Disease Control Advisory Committee on Immunization Practices \[ACIP\]).
* Expected to be available for the duration of the study.
* If born to an HIV-infected woman, participant must not have been breastfed and must have had documentation of 2 negative HIV nucleic acid (RNA or DNA) test results from samples collected on different dates with both collected when greater than or equal to 1 month of age and at least one collected when greater than or equal to 4 months of age, and no positive HIV nucleic acid (RNA or DNA) test; or 2 negative HIV antibody tests, both from samples collected at greater than or equal to 6 months of age.

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 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 were allowed to enroll.
* 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 enrolled, or scheduled to be enrolled in IMPAACT 2011, 2012 or 2013 AND 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 greater than or equal to 6 years of age with HIV-related immunodeficiency, defined as having a most recent CD4 T lymphocyte cell count less than 300 cells/mm\^3. CD4 T lymphocyte count must have been measured within 6 months prior to enrollment, or
  * a person age 1 year up to less than 6 years with HIV-related immunodeficiency, defined as having a most recent CD4 T lymphocyte cell percentage less than 25 or CD4 T lymphocyte count less than 750 cells/mm\^3 (if both values available, use the lower of the two). CD4 T lymphocyte parameter must have been measured within the 6 months prior to enrollment; or
  * a person age less than 1 year with HIV-related immunodeficiency, defined as having a most recent CD4 T lymphocyte cell percentage less than 30 or CD4 T lymphocyte count less than 1000 cells/mm\^3 (if both values available, use the lower of the two). CD4 T lymphocyte parameter must have been measured within the 6 months prior to enrollment; or
  * a person who has received chemotherapy within the 12 months prior to enrollment; or
  * a person receiving immunosuppressant agents; or
  * a person living with a solid organ or bone marrow transplant.

Verbal report of CD4 T cell lymphocyte is sufficient documentation if the parent/guardian is confident of history.

* 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 (rectal temperature of greater than or equal to 100.4°F (38°C)), 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

Permitted concomitant medications (prescription or non-prescription) include nutritional supplements, medications for gastroesophageal reflux, eye drops, and topical medications, including (but not limited to) cutaneous (topical) steroids, topical antibiotics, and topical antifungal agents.

* Receipt of salicylate (aspirin) or salicylate-containing products within the 28 days prior to enrollment.
* 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.
D: Inclusion Criteria:

* Participant is at least 6 months but less than 25 months of age at the time of inoculation
* Parent or guardian who demonstrates their understanding of the study, signs the informed consent, and agrees 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 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 has received routine immunizations appropriate for age, administered:

  1. at least 2 weeks prior to study vaccine inoculation (inactivated and subunit vaccines and rotavirus vaccine) OR
  2. at least 4 weeks prior to study vaccine inoculation (all other live vaccines)
* Participant is expected to be available for the duration of the study

Exclusion Criteria:

* Known or suspected impairment of immunological functions, including maternal history of positive HIV test
* Receipt of immunosuppressive therapy including systemic corticosteroids within the past 30 days. NOTE: Topical steroids, topical antibiotics, and topical antifungal medications are acceptable.
* Bone marrow/solid organ transplant recipient
* 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 any anaphylactic reaction
* Known hypersensitivity to any vaccine component
* Lung or heart disease, including any wheezing event or reactive airway disease. NOTE: 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 be enrolled.
* Member of a household that contains an immunocompromised individual
* Member of a household that contains infants less than 6 months of age
* 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.

Temporary Exclusion Criteria:

The following are temporary or self-limiting conditions. Once resolved, the participant may be enrolled, if otherwise eligible, and if the period of temporary exclusion has been less than 42 days from screening. Otherwise, the participant will need to be rescreened.

* Participant has a rectal temperature of greater than or equal to 100.4°F on the day of planned vaccination, or URI (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
* Receipt of another investigational vaccine or investigational drug within the prior 28 days of receiving the study inoculation
* Participant has received antibiotics or systemic or nasal steroid therapy for acute illness within the previous 3 days prior to vaccination. NOTE: 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
* Participant born at less than 37 weeks gestation and is currently less than 1 year of age

Answer: C