Safety and Immunogenicity Study of Live Attenuated Indian Rotavirus Vaccine Candidate Strains 116E and I321 in Infants
Condition: Rotavirus Infections
MeSH terms: Rotavirus Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      It has been observed that in children who get a severe rotavirus infection, subsequent
      infections cause either no symptoms or generally only mild or moderate diarrhea. This
      evidence is the basis for developing a vaccine since it suggests that the first infection
      immunizes the child against disease upon re-infection.

      It was found that neonatal avirulent strains 116E and I321 induce protective immunity and
      offer clinical protection for at least one year. Both these strains are well characterized
      and the safety studies have been done in animal models. These candidate vaccine strains have
      been evaluated for safety and immunogenicity in adults and children (2 to 12 years of age) by
      a randomized double blind placebo controlled trial in Cincinnati, USA. In India, the
      diversity of rotavirus strains is greater and there is greater prevalence of malnutrition and
      co-infection with other enteric pathogens. These vaccines have therefore, also been tested in
      India.
    

Detailed description: 
      This study was a phase I randomized, double blind, safety and immunogenicity study of live,
      attenuated neonatal rotavirus vaccine candidate strains 116E or I321 in healthy
      non-malnourished infants aged 8-12 weeks. Informed, written, witnessed consent was obtained
      from the parents before infants were screened at 6 weeks of age. Infants (n=90) were
      randomized (30 per group) to receive one dose of either the 116E or I321 vaccines (10^5
      fluorescence focus units, FFu) or placebo at 8 weeks of age. The rotavirus vaccine was
      administered at a different time than DPT (Diptheria-Pertussis-Tetanus), OPV (Oral Polio
      Vaccine) and HBV (Hepatitis B vaccine) immunization since the trial represented the first
      safety study in infants with these strains. The DPT, OPV and HBV vaccines were given at the
      regular EPI schedule of 6, 10 and 14 weeks with the precautions and techniques routinely in
      place for these.

      The test article was administered orally two weeks after the first DPT, OPV and HBV dose,
      after half an hour of administering 2.5 ml bicarbonate to buffer stomach acidity.

      Evaluation of reactogenicity consisted of daily recording of symptoms reported by the
      mother/caregiver and twice-daily axillary temperature measurements for 14 days post
      administration of vaccine/placebo. Stool specimens were collected before administration of
      vaccine/placebo, twice during the week following administration (days 3 and 7), and at day 28
      after administration to evaluate for vaccine virus shedding. Weekly recording of adverse
      events was also done for the next 2 weeks i.e. on days 21 and 28 post administration of
      vaccine/placebo. If gastrointestinal signs or symptoms occurred any time during the 4 weeks
      observation period, attempts were made to collect stool samples daily (maximum 2 per day)
      while the illness persisted, to be examined for the presence of the vaccine strains.

      Immunogenicity was determined by analysis of sera obtained before immunization and 28 days
      after immunization for changes in titers of rotavirus antibodies.
    

Intervention name(s): 116E AGMK; I321; Placebo
Intervention type(s): Biological; Drug; Drug
Intervention description(s): Single dose of 116E 10^5 FFu; Single dose of I321 10^5 FFu; 1 crystal of potassium permanganate dissolved in the bicarbonate buffer to colour match the vaccine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: rotavirus; vaccine; safety; immunogenicity; infants