Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase I/II Descending Age Double-blinded Randomized Placebo-controlled Dose Escalation Study to Examine the Safety Reactogenicity Tolerability & Immunogenicity of the P2-VP8 Subunit Parenteral Rotavirus Vaccine in Healthy Toddlers & Infants
Brief Summary: This is is a study of a parenteral rotavirus vaccine (P2-VP8 subunit rotavirus vaccine). The study will examine the safety and immunogenicity of this vaccine first in healthy South African toddlers. If the safety profile is deemed appropriate, the study will continue to explore the safety and immunogenicity of the vaccine in healthy South African infants.

The primary safety hypothesis is that the P2-VP8 subunit rotavirus vaccine is safe and well-tolerated in healthy toddlers and infants. The primary immunogenicity hypothesis is that the P2-VP8 subunit rotavirus vaccine is immunogenic in infant participants and will induce an immune response in at least 80% of participants in at least one of the study groups.


Options:
A: Inclusion criteria:

* Healthy infants 6 -14 weeks of age at the time of the first study vaccination with birth weight \> 2000g whose parent/guardian sign a written informed consent and whose parents/guardians can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits).

Exclusion criteria:

* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* Planned administration of a vaccine not foreseen by the study protocol within 14 days before each dose of study vaccine(s) and ending 14 days after.
* Chronic administration (defined as more than 14 days) of immunosuppressants since birth. (Topical steroids are allowed.)
* History of diphtheria, tetanus, pertussis, Hib disease and/ or hepatitis B disease (in all subjects). Only for subjects in Spain: history of meningococcal group C disease. Only for subjects in France and Germany: history of disease caused by Streptococcus pneumoniae.
* History of use of experimental rotavirus vaccine.
* Previous vaccination against diphtheria, tetanus, pertussis, Haemophilus influenzae type b (in all subjects). Only for subjects in Spain: previous vaccination against meningococcal group C. Only for subjects in France and Germany: previous vaccination against Streptococcus pneumoniae.
* Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the GI tract, IS or other medical condition determined to be serious by the investigator.
* Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination (no laboratory testing is required).
* History of allergic disease or reaction likely to be exacerbated by any component of the vaccine.
* Acute disease at the time of enrolment. (Acute disease is defined as the presence of a moderate or severe illness with or without fever. All vaccines can be administered to persons with a minor illness such as mild upper respiratory infection with or without low-grade febrile illness, i.e. Oral temperature \<37.5°C (99.5°F) / Axillary temperature \<37.5°C (99.5°F) / Rectal temperature \<38°C (100.4°F).)
* Gastroenteritis within 7 days preceding the first study vaccine administration (warrants deferral of the vaccination).
* A family history of congenital or hereditary immunodeficiency.
* Administration of immunoglobulins and/or blood products since birth or planned administration during the study period.
* History of any neurologic disorders or seizures.
* Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
B: Inclusion Criteria:

* infants aged 6 to 12 weeks
* born in Brest District, France
* born between Feb 01, 2007 and Nov 19, 2009

Exclusion Criteria:

* contraindication to rotavirus vaccine
C: Inclusion Criteria:

* healthy infants/toddlers as established by medical history and clinical examination before entering study
* age:

  * toddler cohort: \> or = 2 and \<3 years old at the time of enrollment
  * infant cohort: \> or = 6 and \<8 weeks at the time of enrollment
* parental ability and willingness to provide informed consent
* parental intention to remain in the area with the child during the study period.

Exclusion Criteria:

* Presence of fever on the day of enrollment
* Acute disease at the time of enrollment
* Concurrent participation in another clinical trial throughout the entire timeframe for this study
* Presence of malnutrition or any systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrine, immunological, dermatological, neurological, cancer or autoimmune disease) as determined by medical history and/or physical examination that would compromise the participant's health or is likely to result in nonconformance to the protocol
* For infant cohort, history of premature birth (\<37 weeks gestation)
* History of congenital abdominal disorders, intussusception, or abdominal surgery
* Known or suspected impairment of immunological function based on medical history and physical examination
* For infant cohort only, prior receipt of rotavirus vaccine
* A known sensitivity or allergy to any components of the study vaccine
* History of anaphylactic reaction
* Major congenital or genetic defect
* Participant's parents not able, available or willing to accept active weekly follow-up by the study staff
* Has received any immunoglobulin therapy and/or blood products since birth or planned administration during the study period
* History of chronic administration (defined as more than 14 days) of immunosuppressant medications, including corticosteroids. Infants on inhaled or topical steroids may be permitted to participate in the study
* Any medical condition in the parents/infant that, in the judgment of the investigator, would interfere with or serves as a contraindication to protocol adherence or a participant's parents' ability to give informed consent
* HIV infection

  * For toddlers, to be assessed by HIV ELISA
  * For infants, to be assessed by PCR, if mother is not known to be negative (negative test result between 24 weeks gestation and screening)
D: Inclusion Criteria:

* Healthy infants as established by medical history and clinical examination before entering the study.
* Age: 6-8 weeks at the time of enrollment.
* Parental ability and willingness to provide informed consent.
* Parent who intends to remain in the area with the child during the study period.

Exclusion Criteria:

* Presence of diarrhea or vomiting in the previous 72 hours or on the day of enrollment (temporary exclusion)
* Presence of fever on the day of enrollment (temporary exclusion).
* Acute disease at the time of enrollment (temporary exclusion)
* Concurrent participation in another clinical trial throughout the entire timeframe for this study.
* Presence of significant malnutrition (weight-for-height z-score \<-3SD median) or any systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrine, immunological, dermatological, neurological, cancer or autoimmune disease) as determined by medical history and/or physical examination which would compromise the subject's health or is likely to result in nonconformance to the protocol. History of congenital abdominal disorders, intussusception or abdominal surgery
* Known or suspected impairment of immunological function based on medical history and physical examination.
* Household contact with an immunosuppressed individual or pregnant woman.
* Prior receipt of rotavirus vaccine.
* A known sensitivity or allergy to any components of the study vaccine.
* Major congenital or genetic defect.
* History of persistent diarrhea (defined as diarrhea more than 14 days).
* Participant's parents not able, available or willing to accept active weekly follow-up by the study staff.
* Has received any immunoglobulin therapy and/or blood products since birth or planned administration during the study period.
* History of chronic administration (defined as more than 14 days) of immunosuppressants including corticosteroids. Infants on inhaled or topical steroids may be permitted to participate in the study.
* History of any neurologic disorders or seizures.
* Any medical condition in the parents/infant which, in the judgment of the investigator, would interfere with or serves as a contraindication to protocol adherence or a participant's parents' ability to give informed consent.

Answer: C