title: Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian infants: a randomised, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed in these countries. We aimed to assess the efficacy and tolerability of a monovalent human-bovine rotavirus vaccine for severe rotavirus gastroenteritis in low-resource urban and rural settings in India.
  
  
  METHODS
  We did a randomised double-blind, placebo-controlled, multicentre trial at three sites in Delhi (urban), Pune (rural), and Vellore (urban and rural) between March 11, 2011, and Nov 5, 2012. Infants aged 6-7 weeks were randomly assigned (2:1), via a central interactive voice or web response system with a block size of 12, to receive either three doses of oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6-7 weeks, 10 weeks, and 14 weeks. Infants' families, study investigators, paediatricians in referral hospitals, laboratory staff, and committee members were all masked to treatment allocation. The primary outcome was incidence of severe rotavirus gastroenteritis (≥11 on the Vesikari scale). Efficacy outcomes and adverse events were ascertained through active surveillance. Analysis was by intention to treat and per protocol. The trial is registered with Clinical Trial Registry-India (CTRI/2010/091/000102) and ClinicalTrials.gov (NCT01305109).
  
  
  RESULTS
  4532 infants were assigned to receive the 116E vaccine and 2267 to receive placebo, of whom 4354 (96%) and 2187 (96%) infants, respectively, were included in the primary per-protocol efficacy analysis. 71 events of severe rotavirus gastroenteritis were reported in 4752 person-years in infants in the vaccine group compared with 76 events in 2360 person-years in those in the placebo group; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0-66·9; p=0·0013) and 56·4% (36·6-70·1; p<0·0001) in the first year of life. The number of infants needed to be immunised to prevent one severe rotavirus gastroenteritis episode was 55 (95% CI 37-97). The incidence of severe rotavirus gastroenteritis per 100 person-years was 1·5 in the vaccine group and 3·2 in the placebo group, with an incidence rate ratio of 0·46 (95% CI 0·33-0·65). Prevalence of immediate, solicited, and serious adverse events was similar in both groups. One case of urticaria in the vaccine group and one each of acute gastroenteritis and suspected sepsis in the placebo group were regarded as related to the study product. We recorded six cases of intussusception in the vaccine group and two in the placebo group, all of which happened after the third dose. 25 (<1%) infants in the vaccine group and 17 (<1%) in the placebo group died; no death was regarded as related to the study product.
  
  
  CONCLUSIONS
  Monovalent human-bovine (116E) rotavirus vaccine is effective and well tolerated in Indian infants.
  
  
  BACKGROUND
  Department of Biotechnology and the Biotechnology Industry Research Assistance Council, Government of India; Bill & Melinda Gates Foundation to PATH, USA; Research Council of Norway; UK Department for International Development; National Institutes of Health, Bethesda, USA; and Bharat Biotech International, Hyderabad, India.
authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
authors.forename: Nita
authors.initials: N
authors.lastname: Bhandari
authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
authors.forename: Temsunaro
authors.initials: T
authors.lastname: Rongsen-Chandola
authors.affiliation: KEM Hospital Research Centre, Pune, Maharashtra, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Bavdekar
authors.affiliation: Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Jacob
authors.initials: J
authors.lastname: John
authors.affiliation: PATH, New Delhi, India.
authors.forename: Kalpana
authors.initials: K
authors.lastname: Antony
authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
authors.forename: Sunita
authors.initials: S
authors.lastname: Taneja
authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Goyal
authors.affiliation: KEM Hospital Research Centre, Pune, Maharashtra, India.
authors.forename: Anand
authors.initials: A
authors.lastname: Kawade
authors.affiliation: Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Gagandeep
authors.initials: G
authors.lastname: Kang
authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
authors.forename: Sudeep Singh
authors.initials: SS
authors.lastname: Rathore
authors.affiliation: KEM Hospital Research Centre, Pune, Maharashtra, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Juvekar
authors.affiliation: Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Jayaprakash
authors.initials: J
authors.lastname: Muliyil
authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
authors.forename: Alok
authors.initials: A
authors.lastname: Arya
authors.affiliation: KEM Hospital Research Centre, Pune, Maharashtra, India.
authors.forename: Hanif
authors.initials: H
authors.lastname: Shaikh
authors.affiliation: Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Vinod
authors.initials: V
authors.lastname: Abraham
authors.affiliation: Translational Health Science and Technology Institute, Gurgaon, Haryana, India.
authors.forename: Sudhanshu
authors.initials: S
authors.lastname: Vrati
authors.affiliation: National Institutes of Health, Bethesda, MD, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Proschan
authors.affiliation: Blair & Co, Greenwich, CT, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Kohberger
authors.affiliation: Advancing Rotavirus Vaccines Development Project, PATH, France.
authors.forename: Georges
authors.initials: G
authors.lastname: Thiry
authors.affiliation: National Institutes of Health, Bethesda, MD, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Glass
authors.affiliation: Stanford University School of Medicine, USA.
authors.forename: Harry B
authors.initials: HB
authors.lastname: Greenberg
authors.affiliation: National Institutes of Health, Bethesda, MD, USA.
authors.forename: George
authors.initials: G
authors.lastname: Curlin
authors.affiliation: Bharat Biotech International, Genome Valley, Andhra Pradesh, India.
authors.forename: Krishna
authors.initials: K
authors.lastname: Mohan
authors.affiliation: Bharat Biotech International, Genome Valley, Andhra Pradesh, India.
authors.forename: G V J A
authors.initials: GV
authors.lastname: Harshavardhan
authors.affiliation: Bharat Biotech International, Genome Valley, Andhra Pradesh, India.
authors.forename: Sai
authors.initials: S
authors.lastname: Prasad
authors.affiliation: Department of Biotechnology, Government of India, India.
authors.forename: T S
authors.initials: TS
authors.lastname: Rao
authors.affiliation: Vaccine Development Global Program, PATH, USA.
authors.forename: John
authors.initials: J
authors.lastname: Boslego
authors.affiliation: Ministry of Science and Technology, Government of India, India. Electronic address: rajkbhan@gmail.com.
authors.forename: Maharaj Kishan
authors.initials: MK
authors.lastname: Bhan
mesh_terms: D004311:Double-Blind Method; D005260:Female; D005759:Gastroenteritis / Q000517:prevention & control*; D006801:Humans; D007194:India; D007223:Infant; D008297:Male; D012400:Rotavirus Infections / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000627:therapeutic use*
chemical_list: D022243:Rotavirus Vaccines