Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II Randomized, Observer-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Immunogenicity and Safety of Multiple Formulations of an RSV F Particle Vaccine With Aluminum, in Healthy Women of Child-Bearing Age
Brief Summary: The purpose of this study is to evaluate the immunogenicity and safety of multiple formulations of an RSV-F protein nanoparticle vaccine, with aluminum, in healthy women of child-bearing age.


Options:
A: 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.
B: Inclusion Criteria:

Subjects must meet the following criteria to be eligible to participate:

1. Healthy adult females, ≥ 18 and ≤ 35 years of age. "Healthy" shall be defined by the absence of any illness, acute or chronic, that requires ongoing systemic therapy for the control of symptoms or prevention of disability.

   * Subjects on stable (no change in ≥ 3 months) therapy for findings (e.g., hypertension or hyperlipidemia) that are not associated with symptoms or disability are eligible, as are users of hormonal contraceptives.
   * Subjects who receive intermittent prophylaxis for risks associated with asymptomatic findings (e.g., antibiotic prophylaxis prior to dental procedures in a subject with mitral valve prolapse) are eligible.
   * Ongoing therapy will be defined as continuous or, if intermittent, more frequent than once every 3 months (e.g., use of an inhaled bronchodilator for exercise-induced bronchospasm more than once every 3 months). Immunosuppressives are subject to exclusion criterion #5 below.
   * Persons being treated for illnesses or conditions that would become acutely symptomatic or disabling in the absence of treatment are not eligible.
2. Willing and able to give informed consent prior to study enrollment.
3. Able to comply with study requirements.
4. Women who are not surgically sterile must have a negative urine pregnancy test prior to each vaccination; will be advised through the Informed Consent process to avoid becoming pregnant over the duration of the study, and must assert that they will employ an effective form of birth control for the duration of the study. Acceptable forms of birth control are: credible history of continuous abstinence from heterosexual activity, hormonal contraceptives (oral, injectable, implant, patch, ring), double-barrier contraceptives (condom or diaphragm, with spermicide), and IUD.

Exclusion Criteria:

Subjects will be excluded if they fulfill any of the following criteria:

1. Participation in research involving investigational product (drug / biologic / device) within 45 days before planned date of first vaccination.
2. History of a serious reaction to any prior vaccination.
3. Received any vaccine in the 4 weeks preceding the study vaccination; or any RSV vaccine at any time.
4. Any known or suspected immunosuppressive condition, acquired or congenital, as determined by history and/or physical examination.
5. Chronic administration (defined as more than 14 continuous days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the study vaccine. An immunosuppressant dose of glucocorticoid will be defined as a systemic dose ≥10mg of prednisone per day or equivalent. The use of topical, inhaled, and nasal glucocorticoids will be permitted.
6. Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of the study vaccine or during the study.
7. Donated blood within 3 weeks of the planned date of first vaccination.
8. Acute disease at the time of enrollment (defined as the presence of a moderate or severe illness with or without fever, or an oral temperature \>38.0°C on the planned day of vaccine administration).
9. Known disturbance of coagulation.
10. Women who are pregnant or breastfeeding, or plan to become pregnant during the study.
11. Suspicion or recent history (within one year of planned vaccination) of alcohol or other substance abuse.
12. Any condition that in the opinion of the Investigator would pose a health risk to the subject if enrolled or could interfere with evaluation of the vaccine or interpretation of study results (including neurologic or psychiatric conditions deemed likely to impair the quality of safety reporting).
C: 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.
D: 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.

Answer: B