title: Efficacy of a monovalent human-bovine (116E) rotavirus vaccine in Indian children in the second year of life.
abstract: Rotavirus gastroenteritis is one of the leading causes of diarrhea in Indian children less than 2 years of age. The 116E rotavirus strain was developed as part of the Indo-US Vaccine Action Program and has undergone efficacy trials. This paper reports the efficacy and additional safety data in children up to 2 years of age. In a double-blind placebo controlled multicenter trial, 6799 infants aged 6-7 weeks were randomized to receive three doses of an oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6, 10, and 14 weeks. The primary outcome was severe (≥11 on the Vesikari scale) rotavirus gastroenteritis. Efficacy outcomes and adverse events were ascertained through active surveillance. We randomly assigned 4532 and 2267 subjects to receive vaccine and placebo, respectively, with over 96% subjects receiving all three doses of the vaccine or placebo. The per protocol analyses included 4354 subjects in the vaccine and 2187 subjects in the placebo group. The overall incidence of severe RVGE per 100 person years was 1.3 in the vaccine group and 2.9 in the placebo recipients. Vaccine efficacy against severe rotavirus gastroenteritis in children up to 2 years of age was 55.1% (95% CI 39.9 to 66.4; p<0.0001); vaccine efficacy in the second year of life of 48.9% (95% CI 17.4 to 68.4; p=0.0056) was only marginally less than in the first year of life [56.3% (95% CI 36.7 to 69.9; p<0.0001)]. The number of infants needed to be immunized to prevent one episode of severe RVGE in the first 2 years of life was 40 (95% CI 28.0 to 63.0) and for RVGE of any severity, it was 21 (95% CI 16.0 to 32.0). Serious adverse events were observed at the same rates in the two groups. None of the eight intussusception events occurred within 30 days of a vaccine dose and all were reported only after the third dose. The sustained efficacy of the 116E in the second year of life is reassuring.
  
  
  BACKGROUND
  The trial is registered with Clinical Trial Registry-India (# CTRI/2010/091/000102) and Clinicaltrials.gov (# NCT01305109).
authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
authors.forename: Nita
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authors.lastname: Bhandari
authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
authors.forename: Temsunaro
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authors.lastname: Rongsen-Chandola
authors.affiliation: KEM Hospital Research Centre, Pune, Maharashtra, India.
authors.forename: Ashish
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authors.lastname: Bavdekar
authors.affiliation: Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Jacob
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authors.lastname: John
authors.affiliation: PATH-India, India.
authors.forename: Kalpana
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authors.lastname: Antony
authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
authors.forename: Sunita
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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
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authors.affiliation: Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Gagandeep
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authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
authors.forename: Sudeep Singh
authors.initials: SS
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authors.affiliation: KEM Hospital Research Centre, Pune, Maharashtra, India.
authors.forename: Sanjay
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authors.lastname: Juvekar
authors.affiliation: Christian Medical College, Vellore, Tamil Nadu, India.
authors.forename: Jayaprakash
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authors.lastname: Muliyil
authors.affiliation: Centre for Health Research and Development, Society for Applied Studies, New Delhi, India.
authors.forename: Alok
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authors.lastname: Arya
authors.affiliation: KEM Hospital Research Centre, Pune, Maharashtra, India.
authors.forename: Hanif
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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; National Institute of Immunology, New Delhi, India.
authors.forename: Sudhanshu
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authors.lastname: Vrati
authors.affiliation: National Institutes of Health, Bethesda, MD, USA.
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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
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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 Limited, Genome Valley, Andhra Pradesh, India.
authors.forename: Krishna
authors.initials: K
authors.lastname: Mohan
authors.affiliation: Bharat Biotech International Limited, Genome Valley, Andhra Pradesh, India.
authors.forename: G V J A
authors.initials: GV
authors.lastname: Harshavardhan
authors.affiliation: Bharat Biotech International Limited, Genome Valley, Andhra Pradesh, India.
authors.forename: Sai
authors.initials: S
authors.lastname: Prasad
authors.affiliation: Department of Biotechnology, Ministry of Science and Technology, 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: D000818:Animals; D002417:Cattle; D004311:Double-Blind Method; D005759:Gastroenteritis / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D007115:Immunization Schedule; D007194:India; D007223:Infant; D007443:Intussusception / Q000139:chemically induced; D016865:Reassortant Viruses; D012401:Rotavirus; D012400:Rotavirus Infections / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D022243:Rotavirus Vaccines
keywords: Gastroenteritis; Rotavirus; Vaccine efficacy