Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Randomized, Controlled, Observer-blind, Multicenter Study to Evaluate the Safety, Tolerability and Immunogenicity of Two Doses of a Monovalent A/H5N1 Influenza Vaccine Adjuvanted With MF59 (Fluad-H5N1) in Adult and Elderly Subjects
Brief Summary: The present study, phase III, randomized, controlled, observer-blind, multicenter study, will evaluate safety, tolerability and immunogenicity of two doses of an adjuvanted monovalent influenza vaccine compared with an adjuvanted interpandemic trivalent influenza vaccine in a population of healthy adult and elderly subjects.


Options:
A: Inclusion Criteria:

* Pregnant women age \> 18 years to \< 39 years.
* Gestational age ≥ 20 weeks to \< 34 weeks documented by the approximate date of the last menstrual period and corroborated by physical exam.
* Documented to be HIV-infected on two assays prior to study-enrollment.
* Able to understand and comply with planned study procedures.
* Provides written informed consent prior to initiation of study.

Exclusion Criteria

* In HIV-infected women features of WHO clinical category 3 or 4 of AIDS at the time of enrollment.
* Receipt of TIV, other than through the study, during the current influenza season documented by medical history or record.
* Receipt of any live licensed vaccine ≤ 28 days or inactivated licensed vaccine ≤ 14 days prior to study-vaccine.
* Receipt of a non-licensed agent (vaccine, drug, biologic, device, blood product, or medication) ≤ 28 days prior to vaccination in this study, or expects to receive another non-licensed agent before delivery unless study approval is obtained.
* Any significant (in the opinion of the site investigator) acute illness and/or oral temperature greater than or equal to 38 degrees C ≤ 24 hours prior to study entry.
* Use of anti-cancer systemic chemotherapy or radiation therapy ≤ 48 weeks of study enrollment, or has immunosuppression as a result of an underlying illness or treatment.
* Long term use of glucocorticoids, including oral or parenteral prednisone ≥ 20 mg/day or equivalent for more than 2 consecutive weeks (or 2 weeks total) ≤ 12 weeks of study entry, or high-dose inhaled steroids (\> 800 mcg/day of beclomethasone dipropionate or equivalent) ≤ 12 weeks before study entry (nasal and topical steroids are allowed).
* Receipt of corticosteroids for preterm labor ≤ 14 days before study entry.(ix) Receipt of immunoglobulin or other blood products (with exception of Rho D immune globulin) ≤ 12 weeks prior to enrollment in this study or is scheduled to receive immunoglobulin or other blood products (with the exception of Rho D immune globulin) during pregnancy or for the first 24 weeks after delivery.
* Receipt of IL2, IFN, GMCSF or other immune mediators ≤ 12 weeks before enrollment.
* Uncontrolled major psychiatric disorder.
* History of a severe adverse reaction to previous TIV.
* Any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
* Pregnancy complications (in the current pregnancy) such as pre-term labor, hypertension (systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mm Hg) or pre-eclampsia
B: Inclusion Criteria:

* Subjects 18 years of age and older who were mentally competent and who had signed an informed consent form after having received a detailed explanation of the study protocol;
* In good health as determined by:

  1. medical history,
  2. physical examination,
  3. clinical judgment of the Investigator;
* Able to understand and comply with all study procedures and to complete study diaries, could be contacted, and were available for study visits;

Exclusion Criteria:

* Receipt of another investigational agent within 4 weeks;
* Laboratory-confirmed influenza disease within 6 months prior to Visit 1;
* Receipt of influenza vaccination for current season 2008/2009;
* Experienced any acute disease or infection requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis was acceptable) within the past 7 days;
* Experienced fever (defined as axillary temperature ≥38.0°C) within 7 days prior to Visit 1;
* Pregnant or breastfeeding;
* Females of childbearing potential who were sexually active and had not used or did not plan or refused to use an acceptable method of birth control during the active phase of the study (at least up to three weeks after last vaccine injection);
* Any serious disease, such as: cancer, autoimmune disease (including rheumatoid arthritis); diabetes mellitus type I and type II; diabetes relating to genetic defects/syndromes, diseases of the exocrine pancreas or infections; advanced arteriosclerotic disease; severe chronic obstructive pulmonary disease (COPD), i.e. GOLD stages 3 and 4; acute or progressive hepatic disease and renal disease; congestive heart failure; Body Mass Index (BMI) ≥35 kg/m2 where BMI reflects obesity and not high muscle mass;
* History of progressive or severe neurologic disorders, of any neurological symptoms or signs, or anaphylactic shock following administration of any study vaccine;
* Bleeding diathesis;
* Surgery planned during the study period;
* Hypersensitivity to eggs, chicken protein, chicken feathers, influenza viral protein, neomycin or polymyxin or any other component of the study vaccines;
* Known or suspected impairment/alteration of immune function, for example, resulting from:

  1. receipt of immunosuppressive therapy (any corticosteroid therapy or cancer chemotherapy) or other immunosuppressive agents within the past 60 days and for the full length of the study;
  2. receipt of immunostimulants;
  3. receipt of parenteral immunoglobulin preparation, blood products and/or plasma derivates within the past 3 months and for the full length of the study;
  4. suspected or known HIV infection or HIV-related disease;
* Receipt of non study vaccines (with the exception of post-exposure vaccination in a medical emergency, e.g. hepatitis, rabies, tetanus) within 3 weeks prior to Visit 1 or planned vaccination within 3 weeks following the last study vaccination;
* History of (or current) drug or alcohol abuse that in the investigator's opinion would interfere with safety of the subject or the evaluation of study objectives;
* Members of research staff and their relatives;
* Any condition, which, in the opinion of the Investigator, might interfere with the evaluation of the study objectives.
C: Inclusion Criteria:

* Good health by history and physical exam
* Reliable access to a telephone
* Study comprehension and informed consent

Exclusion Criteria:

* Systolic BP \>/= 140; diastolic BP \>/= 90
* Uncontrolled medical or psychiatric illness (change in last 3 months)
* Cancer, or treatment for cancer within 3 years
* Cardio-pulmonary disease requiring chronic treatment
* Insulin dependent diabetes mellitus
* Renal dysfunction (creatinine \>/= 1.7 mg/dL)
* Hemoglobinopathies
* Clotting disorders that increase the risk of IM injections
* Immunosuppressive illnesses or drugs
* History of demyelinating disease (esp. Guillian-Barre syndrome)
* Employment in professions at high risk for influenza transmission
* Household contact with high-risk individuals
* Receipt of:

  a) Immunosuppressive drugs i) systemic glucocorticoids \>/= 10 mg prednisone per day ii) cytotoxic drugs b) Investigational drugs within 30 days before, or planned during, the study c) Blood products within 3 months before, or planned during, the study d) Influenza vaccine within 9 months before the study e) Other vaccines within 30 days before, or planned during, the study
* History of:

  1. Severe reactions to other influenza vaccines
  2. Allergy to egg proteins
  3. Sensitivity to mercurials
* Pregnancy/ high risk of pregnancy

  1. Positive urine pregnancy test before treatment
  2. Women of child-bearing potential without credible contraceptive plan
D: Inclusion Criteria:

* Age 18-49 years
* Available for clinic visits at Tufts-New England Medical Center
* Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) obtained
* Ability of participant to understand and comply with the requirements of the protocol

Exclusion Criteria:

* History of any medical conditions for which the CDC states should not be vaccinated with LAIV (asthma, reactive airways disease, other chronic disorders of the pulmonary or cardiovascular systems; metabolic diseases such as diabetes, renal dysfunction, and hemoglobinopathies; or persons with known or suspected immunodeficiency diseases)
* Self-reported vaccination with the influenza vaccine for the current influenza season (2007-8); vaccination with any vaccine within the one month period prior to study enrollment or intent to receive any other vaccine during the study period; hypersensitivity to any influenza vaccine components including thimersol or egg or Guillain-Barre syndrome
* Self-reported treatment with immunomodulator/immunosuppressor drugs (interleukins, corticosteriods (oral or inhaled)), G(M)-CSF in 4 weeks before enrollment or self-reported history of IL-2 administration within 5 years; use of theophylline preparations or warfarin because of the theoretical possibilities of enhanced drug effects and toxicities following influenza vaccination; medication use that might affect the immune response to a vaccine or effects of LGG (no antibiotics during the previous 4 weeks)
* Current alcohol, substance abuse, or systemic/psychiatric illness that potentially could interfere with compliance and ability to make study visits
* Health care or day care workers or close contacts with immunosuppressed persons because of the theoretical risk that LAIV could be transmitted to the immunosuppressed person and cause disease, per CDC recommendations
* Use of LGG or other probiotics in 4 weeks before enrollment. Yogurt consumption is not an exclusion criteria, but subjects will be asked to avoid consumption of other lactobacilli and probiotic organisms during the study period
* Abnormalities upon physical examination
* Acute febrile illness on day of intended immunization - immunization deferred until illness resolved
* Routine laboratory tests outside the limits outlined for this study:

  1. hemoglobin \>=11.5g/dL for women; \>=13.5 g/dL for men
  2. WBC 3,300-12,000 cells/mm\^3
  3. Differential within normal range
  4. Platelets 125,000-550,000 /mm\^3
  5. ALT \<= upper limit of normal
  6. Serum creatinine \<= upper limit of normal
  7. Normal urinalysis (negative glucose, negative or trace protein, and negative or trace hemoglobin)
  8. Negative beta-HCG pregnancy test (urine or serum) for women presumed to be of reproductive potential because LAIV is contraindicated in pregnant women
  9. negative HIV test
  10. negative hepatitis B surface antigen
  11. negative anti-HCV

Answer: B