title: Lot-to-lot consistency of live attenuated SA 14-14-2 Japanese encephalitis vaccine manufactured in a good manufacturing practice facility and non-inferiority with respect to an earlier product.
abstract: We conducted a four-arm, double-blind, randomized controlled trial among 818 Bangladeshi infants between 10 and 12 months of age to establish equivalence among three lots of live attenuated SA 14-14-2 JE vaccine manufactured by the China National Biotec Group's Chengdu Institute of Biological Products (CDIBP) in a new Good Manufacturing Practice (GMP) facility and to evaluate non-inferiority of the product with a lot of the same vaccine manufactured in CDIBP's original facility. The study took place in two sites in Bangladesh, rural Matlab and Mirpur in urban Dhaka. We collected pre-vaccination (Day 0) and post-vaccination Day 28 (-4 to +14 days) blood samples to assess neutralizing anti-JE virus antibody titers in serum by plaque reduction neutralization tests (PRNT). Seroprotection following vaccination was defined as a PRNT titer ≥1:10 at Day 28 in participants non-immune at baseline. Follow-up for reactogenicity and safety was conducted through home visits at Day 7 and monitoring for serious adverse events through Day 28. Seroprotection rates ranged from 80.2% to 86.3% for all four lots of vaccine. Equivalence of the seroprotection rates between pairs of vaccine lots produced in the new GMP facility was satisfied at the pre-specified 10% margin of the 95% confidence interval (CI) for two of the three pairwise comparisons, but not for the third (-4.3% observed difference with 95% CI of -11.9 to 3.3%). Nevertheless, the aggregate seroprotection rate for all three vaccine lots manufactured in the GMP facility was calculated and found to be within the non-inferiority margin (within 10%) to the vaccine lot produced in the original facility. All four lots of vaccine were safe and well tolerated. These study results should facilitate the use of SA 14-14-2 JE vaccine as a routine component of immunization programs in Asian countries.
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh. Electronic address: kzaman@icddrb.org.
authors.forename: K
authors.initials: K
authors.lastname: Zaman
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
authors.forename: Abu Mohd
authors.initials: AM
authors.lastname: Naser
authors.affiliation: PATH, Washington, DC, USA.
authors.forename: Maureen
authors.initials: M
authors.lastname: Power
authors.affiliation: PATH, Washington, DC, USA.
authors.forename: Mansour
authors.initials: M
authors.lastname: Yaich
authors.affiliation: Chengdu Institute of Biological Products, Co., Ltd., Chengdu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: PATH, Washington, DC, USA.
authors.forename: Amy Sarah
authors.initials: AS
authors.lastname: Ginsburg
authors.affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh; Stanford University, Palo Alto, CA, USA.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Luby
authors.affiliation: Institute of Epidemiology Disease Control and Research (IEDCR), Dhaka, Bangladesh.
authors.forename: Mahmudur
authors.initials: M
authors.lastname: Rahman
authors.affiliation: Centers for Disease Control and Prevention (CDC), Atlanta, GA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Hills
authors.affiliation: GVK Biosciences Private Limited, Hyderabad, India.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Bhardwaj
authors.affiliation: PATH, Washington, DC, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Flores
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001459:Bangladesh; D004311:Double-Blind Method; D004672:Encephalitis, Japanese / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007223:Infant; D022321:Japanese Encephalitis Vaccines / Q000592:standards* / Q000627:therapeutic use*; D008297:Male; D009500:Neutralization Tests; D014613:Vaccines, Attenuated / Q000592:standards / Q000627:therapeutic use
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022321:Japanese Encephalitis Vaccines; D014613:Vaccines, Attenuated
keywords: Bangladesh; Children; Immunogenicity; Japanese encephalitis vaccine