Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized, Doubleblind, Placebo-controlled Trial in Healthy Adults of Safety and Immunogenicity of 2 Intranasal Doses of SynGEM®, an RSV Candidate Vaccine Containing F Glycoprotein Linked to a Bacterium-like-Particle (BLP) Carrier
Brief Summary: The study is a double-blind (within dose level), placebo-controlled Phase I study to assess the safety, reactogenicity and tolerability of two intranasal dose levels of SynGEM®: a low dose level (140 μg F-protein/2mg BLPs) and a high dose level ( 350 μg F-protein/5mg BLPs), each administered twice according to a prime-boost schedule 28 days apart at Day 1 and Day 29. The two dose levels will be recruited sequentially.

Immunogenicity end-points will include assessment of humoral and cellular responses at selected time-points.


Options:
A: 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
B: Inclusion Criteria:

1. Male or female aged 18 - 49 years inclusive.
2. Able to give written informed consent to participate.
3. Comprehension of the study requirements, expressed availability for the required study period, and ability to attend scheduled visits.
4. Healthy, as determined by medical history, physical examination, vital signs, and clinical judgment.
5. Must have acceptable laboratory parameters\* within 28 days before Day 1. Acceptable laboratory parameters are defined as follows:

   A. Hemoglobin, Red Blood Cell (RBC) count and hematocrit: within laboratory normal sex-specific range.

   B. White Blood Cell (WBC) count within the normal laboratory range C. Sodium and potassium within laboratory normal range D. Total bilirubin within laboratory normal range E. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST): ≤1.1x institutional ULN.

   F. Serum creatinine: ≤1.1x institutional upper limit of normal (ULN).

   \*Note: If the acceptable laboratory screening parameters listed above are out of the above defined range, repeat of screening tests is permitted once, provided there is an alternative explanation for the out-of-range value. Out of range results for laboratory tests either listed or not in Section 8.6.3 other than those covered in the list above are acceptable if considered not clinically significant by the Investigator.
6. A Body Mass Index (BMI) between 18 and 32, inclusive. BMI = weight (kg)/height2 (m2).
7. Women of childbearing potential must have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test at screening and a negative urine β-hCG pregnancy test within 24 hours preceding receipt of each dose and agree to practice, if not already practicing, highly effective birth control measures from 28 days before the prime vaccination until at least 90 days after the boost vaccination. For women already practicing highly effective birth control measurements for at least 28 days at screening start, recruitment can occur as soon as all screening procedures are completed. The following birth control measure will be considered highly effective:

   1. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device, intrauterine hormone releasing system, bilateral tubal ligation, vasectomized partner (if the partner is the sole sexual partner and has received medical assessment of the surgical success).
   2. True abstinence: when this is in line with the preferred and usual lifestyle of the subject. \[Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial, and withdrawal are not acceptable methods of contraception\].
   3. If not heterosexually active at screening, must agree to practice highly effective birth control measures described above if they become heterosexually active from that moment onwards until at least 90 days after the boost vaccination.
   4. Agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction from the start of screening onwards until at least 90 days after the boost vaccination.
8. Women of non-childbearing potential, defined as postmenopausal (\>45 years of age with amenorrhea for ≥2 years; for female of \>45 years of age with amenorrhea for more than 6 months but less than 2 years confirmation of a serum follicle stimulating hormone (FSH) \>40 mIU/mL will be required to consider them of non-childbearing potential) or surgically sterile (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), are not required to use the birth control methods as described in Inclusion Criterion #7.
9. A man who has not had a vasectomy with medical assessment of the surgical success and is sexually active with a woman of childbearing potential must agree to consistently use a barrier method of birth control, such as condom with spermicidal foam/gel/film/cream/suppository. Men must also agree not to donate sperm from the first study vaccine administration (Day 1) until 90 days after the boost vaccination.
10. Subjects must be willing to provide verifiable identification and their National Insurance/Passport number for the purpose of The Over-volunteering Prevention System (TOPS) registration.
11. Subject must have a means to be contacted.

Exclusion Criteria:

1. History of acute respiratory disease in the 30 days preceding start of screening or documented infection with RSV in the previous 3 months.
2. Any chronic disease of the nasal cavity such as chronic hypertrophic or atrophic rhinitis, chronic sinusitis, ozena, Wegener's granulomatosis or granulomatosis with polyangiitis.
3. History of asthma or chronic obstructive pulmonary disease.
4. Presence of significant uncontrolled medical or psychiatric illness (acute or chronic). This includes institution of a new medical or surgical treatment, or a significant dose alteration for uncontrolled symptoms or drug toxicity within 3 months of screening.
5. Subjects who are positive for hepatitis B surface antigen, hepatitis C antibodies or HIV.
6. Pregnant or breastfeeding women, or planning to become pregnant while enrolled in the study or within 90 days after the boost vaccination.
7. Cancer, or treatment for cancer, within 3 years, excluding basal cell carcinoma or squamous cell carcinoma of the skin, which is allowed.
8. Presence of any medical condition that may be associated with impaired immune responsiveness, including diabetes mellitus.
9. Presently receiving or history of receiving, during the preceding 3-month period, any medications or other treatments that may adversely affect the immune system such as allergy injections, immune globulins, interferon, immunomodulators, cytotoxic drugs or other drugs known to be frequently associated with significant major organ toxicity, or systemic corticosteroids (oral or injectable). Topical corticosteroids are allowed.
10. Receipt of any intranasal administration of drug or vaccine within the 30 days prior to the first administration of study vaccine or plans to receive any intranasal administration of drug or vaccine until the end of study visit.
11. Receipt of live attenuated vaccine within 30 days of first SynGEM® administration or plans to receive within 30 days after the last study vaccine administration, and receipt of any other vaccine within 15 days of first SynGEM® administration or plans to receive within 15 days after the last study vaccine administration.
12. Positive history of illicit drug use, of drug or alcohol abuse within the previous 6 months.
13. History of anaphylactic type reaction to injected vaccines.
14. History of allergic rhinitis or of allergy to food.
15. History of allergy to insect bites, latex, pollens, house dust mites that are considered significant by the Investigator.
16. Treatment with another investigational medicinal product (IMP) within 3 months prior to screening or with more than 2 IMPs in the past year.
17. Receipt of blood or blood products 8 weeks prior to vaccination or planned administration during the study period.
18. Loss of ˃ 500 mL blood within 3 months prior to screening.
19. Any major neurological disease, including migraine
20. Any condition that, in the Investigator's opinion, might interfere with the primary study objectives.
21. Acute disease within 72 hours prior to vaccination, defined as the presence of a moderate or severe illness (as determined by the Investigator through medical history and physical examination) with or without fever, or a fever \>38ºC does not represent an absolute exclusion criterion, but an exclusion criterion at that moment in time. Prime vaccination can be re-scheduled as deemed necessary by the Investigator.
C: * 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.
D: Inclusion Criteria:

* Parents/guardians who demonstrate their understanding of the study (by taking a multiple choice questionnaire), sign the informed consent, and 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 within 42 days prior to enrollment/immunization
* Participant's history has been reviewed and participant has undergone a physical examination indicating that s/he is in good health
* In the view of the site investigator, the participant has received routine immunizations appropriate for their age
* Participant is expected to be available for the duration of the study
* For children born to HIV-infected women: two negative polymerase chain reaction (PCR) tests with one collected when greater than 1 month of age and one collected when greater than 4 months old, and no positive HIV PCR test; or two negative HIV antibody tests

Exclusion Criteria:

* Known or suspected impairment of immunological functions or HIV infection
* Receipt of immunosuppressive therapy including systemic corticosteroids within 30 days of study entry. NOTE: Topical steroids, topical antibiotic, and topical antifungal medications are acceptable within 24 hours of enrollment. May be reassessed after symptoms have resolved.
* 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 infant less than 6 months of age
* Member of a household that contains an immunocompromised individual (including, but not limited to: those with HIV-related immunodeficiency, defined as CD4 less than 300, or less than 15% if less than 5 years of age, measured within the previous 6 months; or any household members who have received chemotherapy within the last 12 months). Verbal report is sufficient documentation if the parent/guardian is confident of history.
* 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.
* 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
* 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, or is scheduled to receive any immunization in the 28 days after enrollment
* Receipt of another investigational vaccine or investigational drug within 28 days of receiving this investigational RSV vaccine
* Participant has received antibiotics or systemic or nasal steroid therapy or other prescription medications for acute illness within 3 days of study entry. 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
* Infants born at less than 37 weeks gestation and less than 1 year of age

Answer: B