Phase I/II Descending Age Study of P2VP8 Subunit Parenteral Rotavirus Vaccine in Healthy Toddlers and Infants

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

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.

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)