Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase I Study of the Safety and Immunogenicity of a Single Dose of the Recombinant Live-Attenuated Respiratory Syncytial Virus Vaccine RSV LID ΔM2-2, Lot RSV#007A, Delivered as Nose Drops to RSV-Seronegative Infants and Children 6 to 24 Months of Age
Brief Summary: Respiratory syncytial virus (RSV) is a common cause of illness in infants and children around the world. This study will evaluate the safety and immune response to an RSV vaccine in RSV-seronegative infants and children.

This study is a companion study to IMPAACT 2000.


Options:
A: Inclusion Criteria:

* 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 any study of an RSV vaccine developed by the Laboratory of Infectious Diseases (LID) (NIAID, NIH) 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 \[ACIP\]). Note: if rotavirus immunization was delayed, "catch-up" rotavirus immunization was indicated only if the participant was age-eligible per 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 4 weeks of age and at least one collected when greater than or equal to 16 weeks 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 24 weeks 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 was 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 immunoglobulin \[IG\] or RSV monoclonal antibody \[mAb\]).
* 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 diagnosed wheezing.
* Member of a household that contained, or would contain, an infant who was less than 6 months of age at the enrollment date through Day 28.
* Member of a household that contains another child who was, or was scheduled to be, enrolled in IMPAACT 2011, 2012 or 2013 or another study evaluating an intranasal live-attenuated RSV vaccine, AND there had been or would 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 contained an immunocompromised individual, including, but not limited to:

  * a person who was 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 are 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 are 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 had 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 was sufficient documentation if the parent/guardian was confident of history.

* Attended a daycare facility and shared a room with infants less than 6 months of age, and parent/guardian was 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 inactivated 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:

  * inactivated 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.
B: 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
C: Inclusion Criteria:

* Between 42 and 55 days of age at the time of enrollment.
* Healthy infant free of chronic or serious medical condition as determined by history and physical examination at the time of study enrollment.
* Parents/guardians of each subject are able to understand and follow study procedures and agree to participate in the study by providing parental/guardian permission.

Exclusion Criteria:

* If child has previously had intussusception or abdominal surgery.
* Use of any immunosuppressive drugs or immunoglobulin and/or blood product use since birth or anticipated during study period.
* Current enrollment in any other intervention trial or use of any investigational drug or vaccine throughout the study period.
* Birthweight less than 2000 grams or gestation \< 36 weeks, if this information is available.
* Any subject who reports plan to leave the study area before the completion of the study (i.e., relocation, migration, etc.).
* Another child living in the same compound is already enrolled in the trial (i.e., only one participant can be enrolled per compound).
* After the rotavirus vaccine is introduced into the routine EPI system in Navrongo: Another child in the compound is less than 16 weeks of age.
* The child has received rotavirus vaccine outside of this study.
D: * INCLUSION CRITERIA:

  1. 18 to 50 years of age.
  2. Willing and able to complete the informed consent process.
  3. Available for clinic visits through 44 weeks after enrollment.
  4. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
  5. Willing to donate blood and mucosal samples to be stored and used for future research.
  6. In good general health without clinically significant medical history.
  7. Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) less than or equal to 40 within the 56 days prior to enrollment. Laboratory criteria within 56 days prior to enrollment:
  8. White Blood Cell (WBC) and differential either within institutional normal range or accompanied by Principal Investigator (PI) or designee approval.
  9. Platelets = 125,000-500,000/mm\^3.
  10. Hemoglobin within institutional normal range.
  11. Creatinine less than or equal to 1.1 x upper limit of normal (ULN).
  12. Alanine aminotransferase (ALT) less than or equal to 1.25 x ULN.
  13. Negative for HIV infection by an FDA approved method of detection.

      Criteria applicable to women of childbearing potential:
  14. Negative result on a human chorionic gonadotropin pregnancy test on day of enrollment before receiving study product.
  15. Agree to use effective means of birth control from at least 21 days before enrollment through 4 weeks after the last injection.
* EXCLUSION CRITERIA:

Criteria applicable to women of childbearing potential:

1. Breast-feeding or planning to become pregnant through 4 weeks after the last injection.

   Subject has received any of the following:
2. More than 10 days of systemic immunosuppressive medications or cytotoxic medications within the 4 weeks prior to enrollment or any within the 14 days prior to enrollment.
3. Blood products within 16 weeks prior to enrollment.
4. Live attenuated vaccines within 4 weeks prior to enrollment.
5. Inactivated vaccines within 2 weeks prior to enrollment.
6. Investigational research agents within 4 weeks prior to enrollment or planning to receive investigational products while on the study.
7. Current allergen immunotherapy with antigen injections, unless on maintenance schedule.
8. Current anti-tuberculosis(TB) prophylaxis or therapy.

   Subject has any of the following:
9. Serious reactions to vaccines that preclude receipt of study injections as determined by the investigator.
10. Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.
11. Asthma that is not well controlled.
12. Diabetes mellitus (type I or II), with the exception of gestational diabetes.
13. Thyroid disease that is not well controlled.
14. Hypertension that is not well controlled.
15. Evidence of autoimmune disease or immunodeficiency.
16. Idiopathic urticaria within the past year.
17. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws.
18. Malignancy that is active or history of malignancy that is likely to recur during the study.
19. Seizure disorder other than: 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures that have not required treatment within the last 3 years.
20. Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen.
21. Psychiatric condition that precludes compliance with the protocol; past or present psychoses; or within 5 years prior to enrollment, a history of suicide plan or attempt.
22. Any medical, psychiatric, or social condition that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a subject s ability to give informed consent.

Answer: B