Immunogenicity of SA 14-14-2 JE Vaccine
Condition: Healthy Infants
Study type: Interventional
Phase: Phase 4

Summary: 
      The proposed Japanese Encephalitis (JE)Vaccine study is a four-arm double-blind randomized
      controlled single center trial to evaluate, by examining post-vaccination seroprotection
      titers, the lot-to-lot consistency of three lots of JE live attenuated SA 14-14-2 vaccine
      manufactured in a new GMP facility, and to establish non-inferiority of the new vaccine in
      comparison to a single lot of the same vaccine manufactured in the existing facility. The
      study will enroll a total of 1,000 Bangladeshi infants aged 10 to 12 months. In addition to
      providing immunogenicity data, JEV05 will provide local safety data of JE live attenuated SA
      14-14-2 vaccine among Bangladeshi children. This will be the first step to secure licensure
      for this life-saving vaccine in Bangladesh as well as provide data to support WHO
      prequalification of JE live attenuated SA 14-14-2 vaccine.
    

Detailed description: 
      Vaccination is the most effective intervention to prevent JE and its associated morbidity and
      mortality (http://www.who.int.nuvi/Je/en). JE live attenuated SA 14-14-2 vaccine has been
      used in Asia for more than two decades in over 400 million children. Chengdu Institute of
      Biological Products (CDIBP), a Chinese manufacturer, has been producing JE live attenuated SA
      14-14-2 vaccine since 1988. It has been demonstrated to be both safe and immunogenic in
      several observational and case-control studies providing protection for at least 5 years
      following a single dose. JE live attenuated SA 14-14-2 vaccine is licensed for use in China,
      India, Nepal, South Korea, Sri Lanka, and Thailand. Countries that have introduced JE vaccine
      into their national immunization programs have experienced dramatic reductions in JE
      incidence, leading WHO to declare vaccination the preferred JE control strategy.4

      In order for JE live attenuated SA 14-14-2 vaccine to be available for purchase through
      UNICEF and GAVI for broader international use, including in Bangladesh, JE live attenuated SA
      14-14-2 vaccine needs to undergo WHO prequalification. With technical support from PATH,
      CDIBP has established a new GMP facility, Building 208 JE production unit, maintaining WHO
      standards. A GMP Certificate for the new facility was issued on 11/16/2011. This certificate
      provides market authorization to distribute the new vaccine in China. To achieve WHO
      prequalification, JE live attenuated SA 14-14-2 vaccine produced in this new GMP facility
      needs to be shown to be similarly safe and immunogenic to JE live attenuated SA 14-14-2
      vaccine produced in the existing facility, the JE viral vaccine production plant, and needs
      to demonstrate lot-to-lot consistency.

      The proposed JEV05 study is a four-arm double-blind randomized controlled single center trial
      testing the immunogenicity of four lots of JE live attenuated SA 14-14-2 vaccine - three lots
      manufactured in the new GMP facility and one lot from the existing facility - in a total of
      1000 Bangladeshi infants aged 10 to 12 months. The study will be conducted in the Matlab
      Health and Demographic Surveillance System (HDSS) intervention area, a rural site where many
      vaccine trials have been conducted.

      A 5 ml blood sample will be collected from each child before vaccination and at 28 days
      post-vaccination. The sera will be tested using a plaque reduction neutralization test (PRNT)
      with JE neutralizing antibody titers > 1:10 considered seroprotective. The JEV05 trial will
      provide immunogenicity data on the three vaccine lots produced in the new GMP facility
      compared to a vaccine lot produced in the prior existing plant. It will also provide local
      immunogenicity and safety data of JE live attenuated SA 14-14-2 vaccine among Bangladeshi
      children. This will be the first step to secure licensure for this life-saving vaccine in
      Bangladesh as well as provide data to support WHO prequalification of JE live attenuated SA
      14-14-2 vaccine.
    

Intervention name(s): JE Vaccine existing facility; JE vaccine new plant lot 1; JE vaccine new plant lot 2; JE vaccine new plant lot 3
Intervention type(s): Biological; Biological; Biological; Biological
Intervention description(s): Will receive JE live attenuated SA 14-14-2 vaccine manufactured in the existing facility (250 infants).; Will receive Lot 1 JE live attenuated SA 14-14-2 vaccine manufactured in the new GMP facility (250 infants).; Will receive Lot 2 JE live attenuated SA 14-14-2 vaccine manufactured in the new GMP facility (250 infants).; Will receive will receive Lot 3 JE live attenuated SA 14-14-2 vaccine manufactured in the new GMP facility (250 infants).
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Immunogenicity; SA 14-14-2 JE vaccine; Bangladesh