Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase II Randomized, Observer-Blind, Placebo-Controlled, Study to Evaluate the Safety and Immunogenicity of a Respiratory Syncytial Virus (RSV) F Nanoparticle Vaccine With Aluminum, in Healthy Third-trimester Pregnant Women and to Assess the Impact of Maternal Immunization on Infant Safety Through One Year of Life
Brief Summary: The purpose of this study is to evaluate the safety and immunogenicity of an RSV-F protein nanoparticle vaccine, with aluminum, in healthy third-trimester pregnant women and to assess the impact of maternal immunization on infant safety through one year of life.


Options:
A: 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
B: 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.
C: Inclusion Criteria:

Pregnant women must meet all of the following criteria to be eligible to participate:

1. ≥18 and ≤40 years-of-age.
2. Singleton pregnancy of 33 to 35 weeks gestation on the day of planned vaccination.
3. Good general maternal health as demonstrated by:

   * Medical history (including history of adverse reactions to prior vaccines and allergies).
   * Physical examination including at least vital signs (blood pressure, pulse, respirations, and oral temperature); weight; height; examination of the HEENT, cardiovascular, pulmonary, gastrointestinal (abdominal), musculoskeletal, lymphatic, and dermatologic organ systems; and documentation of fetal heart tones.
   * Clinical laboratory parameters including normal blood urea nitrogen, creatinine, ALT, AST, total bilirubin, alkaline phosphatase (ALP), hemoglobin, white blood count, and platelet count; and serologic exclusion of infection with hepatitis B (HBV) and C (HCV) viruses and HIV (as required). Note that normal ranges for vital signs and clinical laboratory parameters will be based on third trimester values published in Sheffield et al. \[2013\] and/or reference ranges for the third trimester of pregnancy of the central laboratory.
4. Documentation that fulfills one of the following:

   * Detailed (level II) second trimester or later anatomic ultrasound with no significant anatomic or growth abnormalities identified; OR
   * Routine second trimester or later ultrasound with no significant anatomic or growth abnormalities identified, PLUS at least one of the following:

     * Normal first trimester screening (based on ultrasound + serum analytes); or
     * Normal cell-free fetal DNA; or
     * Normal chorionic villus sampling (CVS) or amniocentesis; or
     * Normal second trimester maternal serum quadruple screen; or
     * Normal first and second trimester screening using integrated, sequential, or contingency approach; or
     * Abnormal first or second trimester screening followed by normal CVS, amniocentesis, or cell-free fetal DNA.
5. Able to understand, and both willing and physically able to comply with study procedures. This includes anticipation of reasonable geographic proximity to the study clinic and adequate transportation to comply with scheduled and unscheduled study follow-up visits.
6. Able and willing to provide written informed consent for themselves and infant.

Exclusion Criteria:

Pregnant women will be excluded if there is historical, physical examination, or laboratory evidence of any of the following criteria:

1. Symptomatic cardiac or pulmonary disease requiring chronic drug therapy, including hypertension and asthma. Asthma will be exclusionary if the subject is receiving chronic systemic glucocorticoids at any dose or inhaled glucocorticoids at any dose \>500µg per day of beclamethasone or fluticasone, or \>800μg per day of budesonide.
2. Pre-pregnancy body mass index (BMI) of ≥35 or \<18.5.
3. Hemoglobinopathy (including known sickle trait or thalassemias, even if asymptomatic) or blood dyscrasias.
4. Hepatic or renal dysfunction.
5. Established diagnosis of seizure disorder, regardless of therapy.
6. Auto-immune disease or known immunodeficiency syndrome.
7. Endocrine disorders, including (but not limited to) hyperthyroidism, untreated hypothyroidism, and glucose intolerance (e.g., diabetes mellitus type 1 or 2) antedating pregnancy, or occurring during pregnancy and requiring interventions other than diet for control.
8. History of major gynecologic or major abdominal surgery, including bariatric surgery.
9. Known HIV, HBV, or HCV infection, as assessed by serologic tests conducted during the current pregnancy or as a procedure during the screening period of the study.
10. Primary genital herpes simplex (HSV) infection during the current pregnancy.
11. Current alcohol or drug abuse.
12. Documentation that current pregnancy results from fertility treatments, rape, or incest.
13. Documentation that the infant will be a ward of the state or be released for adoption.
14. Neuro-psychiatric illness deemed likely to interfere with protocol compliance, safety reporting, or receipt of pre-natal care; or requiring treatment with psychotropic drugs.
15. History/presence of deep venous thrombosis or thromboembolism, or the use of anticoagulants during pregnancy.
16. Untreated red blood cell allo-immunization.
17. Prior stillbirth or neonatal death, or multiple (≥3) spontaneous abortions.
18. Prior preterm delivery ≤34 weeks gestation or having ongoing intervention (medical/surgical) in current pregnancy to prevent preterm birth.
19. Greater than five (5) prior deliveries.
20. Previous infant with a known genetic disorder or major congenital anomaly.
21. Receipt of investigational drugs or immune globulins (with the exception of prophylactic anti-Rho D immune globulin) within six (6) months prior to the administration of the study vaccine.
22. 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 except for the limit established in exclusion criterion #1.
23. Any other physical, psychiatric or social condition which may, in the investigator's opinion, increase the risks of study participation to the maternal subject or the fetus/infant; or may lead to the collection of incomplete or inaccurate safety data.
D: Inclusion Criteria:

1. Healthy males and non-pregnant females 18 to 45 years of age at time of enrollment.
2. Individuals who have given written consent after the nature of the study has been explained according to local regulatory requirements.
3. Individuals in good health as determined by the outcome of the medical history, physical examination and clinical judgment of the investigator.
4. Individuals who can comply with the study procedures and are available for follow up.

Exclusion Criteria:

1. Individuals with any severe chronic or acute disease.
2. Individuals with a history of illness or with an ongoing illness that may pose additional risk to the subject if he/she participates in the study, including the following:

   * History of any chronic respiratory illness, including current diagnosis of asthma within 2 years, exercise induced wheezing, reactive airway disease, emphysema, chronic bronchitis, cystic fibrosis or chronic obstructive pulmonary disease (COPD).
   * Any respiratory illness within 7 days prior to receiving the first study injection.
   * Any active pulmonary infection or other inflammatory conditions, even in the absence of febrile episodes, within 14 days prior to the first study injection.
   * Hepatitis B or hepatitis C infection.
3. Individuals who have had a malignancy or lymphoproliferative disorder within the past 5 years.
4. Individuals with known or suspected impairment of the immune system including but not limited to HIV, autoimmune disorders, immunosuppressive therapy, and diabetes mellitus.
5. Individuals with any history of progressive or severe neurologic disorder, seizure disorder or Guillian-Barré syndrome.
6. Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
7. Individuals with a BMI \> 35 kg/m2. BMI is to be calculated by the following formula: subject weight at baseline divided by subject height in meters multiplied by the subject height in meters. The numerical result will be rounded to the nearest 0.1.
8. Individuals who are allergic to any of the vaccine components, or with a history of anaphylaxis after vaccination.
9. Individuals who during the 90 days prior to enrollment receive any medications or other treatments that may adversely affect the immune system such as allergy injections, immune globulin, interferon, immunomodulators, cytotoxic drugs or other drugs known to be frequently associated with significant major organ toxicity.
10. Individuals who receive systemic immunosuppressive agents including steroids. Prior corticosteroid therapy should be discontinued 28 days prior to enrollment. Individuals using inhaled or topical corticosteroids will be permitted.
11. Receipt or donation of blood or blood products 8 weeks prior to vaccination or planned receipt or donation during the study period.
12. Individuals participating in any clinical trial with another investigational product 28 days prior to receiving the first study vaccination or intent to participate in another clinical study at any time during the conduct of this study.
13. Individuals who have received any vaccine 28 days prior to enrollment in this study, or who plan to receive any non-study vaccines within 28 days of the second dose of study vaccine.
14. Individuals with any clinically significant abnormal safety laboratory result, as judged by the investigator.
15. If female, 'of childbearing potential', sexually active and has not used any of the 'acceptable contraceptive methods' for at least two months prior to study entry.

    Childbearing potential is defined as status post onset of menarche and not meeting any of the following conditions: menopausal for at least two years; sterile status after bilateral tubal ligation for at least one year, immediately after bilateral oophorectomy or after hysterectomy.

    Acceptable methods of birth control are defined as one or more of the following:
    * Hormonal contraceptives.
    * Barrier each and every time during intercourse.
    * Intrauterine device (IUD).
    * Monogamous relationship with vasectomized partner. Partner must have been vasectomized for at least six months prior to subject's study entry.
16. If female subject of childbearing potential and have a positive urine pregnancy test prior to study vaccinations, or are currently lactating.
17. If female of childbearing potential and sexually active, refusal to use an 'acceptable contraceptive method' through to three weeks after last study vaccination.
18. Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study.
19. Individuals with a history of drug or alcohol abuse within the past 2 years.
20. Individuals who are acting as study personnel or immediate family members or the spouse of study personnel.
21. Individuals with a body temperature ≥38 °C (≥100.4◦F) within 3 days of intended study vaccination.
22. Individuals with any condition that, in the opinion of the investigator, would interfere with the primary study objectives.

Answer: C