Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Phase I/II Study to Evaluate Safety & Reactogenicity of Heat Stable Rotavirus Vaccine, in Healthy Adult; Followed by Evaluation of the Safety, Reactogenicity & Immunogenicity of a 3-dose Series in Infants Age 6-8 Weeks
Brief Summary: Rotaviruses are the leading cause of severe, dehydrating diarrhoea and related deaths in children aged less than 5 years worldwide and are reported to infect nearly every child by the age of 5 years. About 90% of all rotavirus-associated fatalities occur in low income countries in Africa and Asia and are related to poor health care. In view of high global RVGE burden, the World Health Organization (WHO) on 5th June 2009, recommended the inclusion of rotavirus vaccine in all the national immunization programs.

Currently available rotavirus vaccines, RotaTeq® and Rotarix®, are WHO prequalified vaccines which are stable for recommended duration at storage temperature between 2-8 °C. However, if these vaccine are exposed to temperatures above 30 °C, the vaccine has to be discarded due to lost potency. It is very difficult to maintain the cold chain required to conserve the vaccine potency particularly in developing and low income countries, resulting in large amount of vaccine being wasted and in worst case scenario, endangering the lives of potential recipients. The WHO estimates that nearly half of freeze-dried and quarter of liquid vaccines are wasted each year. One of the biggest contributors to this wastage is disruption of the cold chain systems.

Hilleman Labs new Rotavirus vaccine is a lyophilized heat stable rotavirus vaccine comprising of five live attenuated reassortant rotaviruses similar to RotaTeq®. The new heat stable rotavirus vaccine (HSRV) formulation offers a stability profile of 9 months at 45 °C and 12 months at 37 °C. This new heat stable formulation (HSRV) could be transported in non-refrigerated supply chain significantly reducing the cost and complications associated with transporting vaccine to remote corners of the developing world. Heat-stable rotavirus vaccine (HSRV) has a potential to sustain high temperatures frequently encountered in regions where majority of rotavirus burden exists and has potential to partially or completely eliminate cold chain dependence.

The current study has been designed to test for the first time in humans, the safety and tolerability of the new heat stable rotavirus vaccine (HSRV) in adults; followed by safety and immunogenicity in infants of age 6-8 weeks, as compared to the licensed RotaTeq® vaccine.


Options:
A: Inclusion Criteria:

Healthy Adults:

1. Healthy adult subjects of either sex, between 18 to 45 years of age;
2. No apparent signs or symptoms of ill health;
3. Subjects properly informed about the study and having signed the informed consent form (ICF). In case of subjects' inability to read or write, having had the ICF explained to them in the presence of a study independent witness and the witness having signed the ICF;
4. Subjects' availability for the entire period of the study and reachability by study staff for post vaccination follow-up.

Healthy Infants:

1. Healthy infants of either sex, 6-8 weeks of age at the time of enrollment;
2. Born after a gestational period of 36-42 weeks with birth weight ≥ 2kg;
3. Father, mother or other legally authorized representative (guardian) properly informed about the study and having signed the informed consent form (ICF). In case of father's, mother's or other legally acceptable representative's (guardian) inability to read or write, having had the ICF explained to them in the presence of a study independent witness and the witness having signed the ICF;
4. Infant/Parents' or guardian's availability for the entire period of the study and reachability by study staff for post-vaccination follow-up.

Exclusion Criteria:

Healthy adults:

1. Known or suspected impairment of immunological function; and known immunosuppressed family members/household contacts
2. Known hypersensitivity to any component of the rotavirus vaccine;
3. Fever, with axillary temperature ≥38.1 oC (≥100.5 oF) as measured by study staff;
4. History of chronic diarrhea;
5. Clinical evidence of active gastrointestinal illness;
6. Receipt of any IM, oral, or IV corticosteroid treatment in the past 30 days;
7. Subjects' suspected to be HIV, HBV or HCV positive from the available clinical history;
8. Any subject who cannot be adequately followed for safety assessment;
9. Any conditions which, in the opinion of the investigator, might interfere with the evaluation of the study objectives;
10. Subject's inability to maintain diary card;
11. Participation in another clinical trial investigating a vaccine, drug, medical device or medicinal procedure in the 4 weeks preceding the current vaccination trial;
12. Planned participation in another clinical trial during the present trial period;
13. Subjects identified as employees of the investigator or study center, with direct involvement in the proposed study or studies under the direction of that investigator or study center as well as children, adopted or natural, of the employees or Investigator.

Healthy Infants:

1. History of congenital abdominal disorders, intussusception, or abdominal surgery;
2. Infants exhibiting signs of severe malnutrition or Known or suspected impairment of immunological function(s) in subject or his/her immediate family;
3. Developmental delay or neurological disorder;
4. Known hypersensitivity to any component of the rotavirus vaccine;
5. Prior receipt of any rotavirus vaccine;
6. Prior receipt of any dose of Diphtheria, Tetanus, Pertussis, Hepatitis B, Hib or polio virus containing vaccine(s). Birth dose of Hepatitis B and Oral Polio Vaccine is allowed to be administered to the infants as per the local immunization practices. Oral Polio Vaccines administered as a part of the National Pulse Polio Program are allowed to be administered to the infants.
7. Fever, with axillary temperature ≥38.1 oC (≥100.5 oF) as measured by study staff.
8. History of known rotavirus disease, chronic diarrhea, or failure to thrive;
9. Clinical evidence of active gastrointestinal illness including ongoing diarrheal episode (infants with GERD can participate in the study so long as this condition is well controlled with or without medication);
10. Receipt of any IM, oral, or IV corticosteroid treatment in the past 30 days (infants on inhaled steroids may be permitted to participate in the study);
11. Infants residing in a household with an immuno-compromised person (e.g., individuals with a congenital immunodeficiency, HIV infection, leukemia, lymphoma, Hodgkin's disease, multiple myeloma, generalized malignancy, chronic renal failure, nephritic syndrome, organ or bone marrow transplantation, or those receiving immunosuppressive chemotherapy including long-term systemic corticosteroids);
12. Infants already laboratory-confirmed or suspected to be HIV, HBV or HCV positive from the available clinical history or born to mothers known to be HIV, HBV or HCV positive (no specific screening for the purpose of the study would be carried out);
13. Prior receipt of a blood transfusion or blood products, including immunoglobulins, in the past 4 weeks which might interfere with the assessment of the immune response;
14. Any infants who cannot be adequately followed for safety assessment by a home visit;
15. Any conditions which, in the opinion of the investigator, might interfere with the evaluation of the study objectives;
16. Parent/s or guardian of infant unable to maintain symptom diary;
17. Participation in another clinical trial investigating a vaccine, drug, medical device or medicinal procedure in the 4 weeks preceding the current vaccination trial;
18. Planned participation in another clinical trial during the present trial period;
19. Parents/ Guardians/ Legally Authorized Representatives identified as employees of the investigator or study center, with direct involvement in the proposed study or studies under the direction of that investigator or study center as well as children, adopted or natural, of the employees or Investigator.

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B: 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.
C: Inclusion Criteria:

* Healthy male or female infant between, and including, 6 and 12 weeks of age born after a gestation period of 36 to 42 weeks or a birth weight of \>2000g.
* Written informed consent obtained from the parent or guardian of the subject.

Exclusion Criteria:

* Planned administration of oral polio vaccine during the period starting from 2 weeks before each dose of study vaccine(s) and ending 2 weeks after.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
* History of diphtheria, tetanus, pertussis, Hib disease and/ or hepatitis B.
* Previous vaccination against diphtheria, tetanus, pertussis, and/or Haemophilus influenzae type b.
* History of allergic disease
* Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the GI tract or other serious medical condition as determined by the investigator.
* Gastroenteritis within 7 days preceding the study vaccine administration (warrants deferral of the vaccination)
* Previous confirmed occurrence of RV GE.
* Household contact with an immunosuppressed individual or pregnant women.
* Administration of immunoglobulins and/or blood products since birth or planned administration during the study period
D: Inclusion Criteria:

* A male or female infant at least 6 weeks of age and not older than 20 weeks of age at the time of first dose of Rotarix.
* An infant whose parent or guardian's primary residence, at the time of first EPI vaccinations, is a village selected to receive Rotarix.
* Written informed consent obtained from the parent or guardian of the subject, prior to the subject's first study vaccination

Exclusion Criteria:

* Hypersensitivity to the active substance or any component in the vaccine
* Hypersensitivity after previous administration of rotavirus vaccines.
* Previous history of intussusception.
* Subjects with uncorrected congenital malformation of the gastrointestinal tract that would predispose for intussusception.
* Infants with known or suspected immunodeficiency.
* Administration of Rotarix should be postponed in subjects suffering from an acute severe febrile illness only if that illness also results in postponement of other EPI vaccinations.

Answer: A