Immunogenicity and Safety of Inactivated Vero Cell Derived Japanese Encephalitis Vaccine in Thai Children (JE0153)

• Geometric mean titer of NT after primary and booster vaccination [ Time Frame: 28 days after second dose and 28 days after booster vaccination with JEVAC ] [ Designated as safety issue: No ]
  To determine the geometric mean titers (GMT) of neutralizing antibody of JEVAC 1 month after primary and then after booster vaccinations.
• Adverse events of vaccine [ Time Frame: 7, 14, 28 days after each vaccination and throughout the study period for local, solicited systemic, unsolicited systemic and serious adverse events, respectively ] [ Designated as safety issue: Yes ]
  To determine the adverse events of JEVAC
• Neutralizing antibody persistence one year after the primary vaccination [ Time Frame: 1 year after primary vaccination ] [ Designated as safety issue: No ]
  To determine the neutralizing antibody persistence one year after the primary JEVAC vaccination.

• Geometric mean titer of NT after primary and booster [ Time Frame: March 2012 ] [ Designated as safety issue: No ]
  To determine the geometric mean titers (GMT) of neutralizing antibody of JEVACTM 1 month after primary and then after booster vaccinations.
• adverse events of vaccine [ Time Frame: september 2011 ] [ Designated as safety issue: Yes ]
  To determine the adverse events of JEvac TM along the study
• neutralization antibody persistence one year after the primary vaccination [ Time Frame: march 2012 ] [ Designated as safety issue: No ]
  To determine the neutralization antibody persistence one year after the primary JEVACTM vaccination.

Japanese encephalitis (JE) is the main cause of viral encephalitis in many countries of Asia including Thailand. Estimated annual mortality ranges from10,000-15,000 deaths, while the total number of clinical cases is about 50,000. Of these cases, about 50% result in permanent neuropsychiatric sequelae. The disease occurs mostly among children aged <10 years. There is no specific antiviral treatment for JE. Vaccination is the single most important control measure. This study aims to evaluate the immunogenicity and safety of inactivated Vero cell derived JE vaccine (Beijing P-3 strain) produced by Liaoning Cheng Da Biotechnology Co., Ltd, China "JEVAC" in Thai children.

152 healthy Thai children aged between 1-3 years will be vaccinated with "JEVAC" in a dose of 0.5 mL. subcutaneously on Day 0, 1-4 weeks later and a booster vaccination at one year (totally 3 doses). Two mL. of blood will be drawn on Day 0, 4 weeks after second dose, at one year on booster vaccination day and 4 weeks after the booster (totally 8 mL. of 13 months study period) for determination of JE neutralizing antibodies (PRNT50) using Beijing P3 strain. Adverse events will be observed for 28 days after each vaccination. Serious adverse events will be observed throughout the study period.

152 subjects illegible for the inclusion and exclusion criteria were enrolled into the study from 3rd May 2010 to 10th August 2010. The male/ female ratio was 79/73 (1.08). The mean (SD) age was 14.4 months (3.8 months).

All subjects received 1st vaccination according to the protocol without any immediate reactions. One subject was terminated from the study after the 1st dose of vaccine because the subject refused blood drawing without any adverse reaction related to the vaccine. One hundred and fifty one subjects received 2nd vaccination and blood drawn. One subject came late for blood drawing (Day 80 after 2nd vaccination) because he was traveling outside the study area.

On Day 0 (before vaccination) 5/152 subjects had detectable neutralizing antibody to Japanese encephalitis virus (> 1/10 dilution). One month after 2nd vaccination all subjects were seroconverted and seroprotected (100%). The geometric mean titer was 169.81 (95% confidence interval 121-2410). If those 5 initially seropositive subjects were excluded, the geometric mean titer was 150.01 (95% confidence interval 198-376). Among 5 subjects who were seropositive on Day 0, four subjects had secondary immune responses while one subject had primary immune response.

All adverse reactions (AEs) occurring within 28 days after each vaccination were recorded and reviewed. Among local AEs, 1 case (0.7%) had mild ecchymosis at injection site after 1st vaccination and 1 case (0.7%) had mild tenderness after 2nd vaccination.

The most common solicited systemic AE was fever which accounted for 20% after each vaccination. The second and third common solicited systemic AEs were vomiting and poor appetite, respectively. One subject each was complained by parent to have dyspnea and ataxia. However, these symptoms were self-limited and might not relate to the study vaccine. The most common unsolicited AE was upper respiratory tract infection (7.3%) followed by acute gastroenteritis (3.3%).

Up to December 2011, there were 9 serious adverse event reports. All events were classified as SAEs requiring hospitalization. The 3 major diagnoses were pneumonia, acute gastroenteritis and febrile convulsion.

Inclusion Criteria:

1. Healthy Thai children aged 1- 3 years
2. No previous history of JE vaccination
3. Available for all visited schedule in the study period.
4. Written inform consent signed by a parent or guardian

Exclusion Criteria:

1. Known serious underlying diseases such as nervous system, heart, kidney and liver diseases.
2. Known hypersensitivity to JE vaccine composition such as human albumin, dextran 40, etc.
3. Previous history of JE disease.
4. Receive the blood component within the past 3 months,
5. Known history of immunocompromised conditions such as HIV/AIDS, malignancy.
6. Under treatment of immunosuppressive drugs such as systemic corticosteroid and anti-neoplastic drug.
7. Febrile illness (temperature ≥37.5°C) or acute illness/infection on the day of vaccination
8. Plan to leave the study area before the end of study period.
9. Participating in other clinical trials.

• Liaoning Cheng Da Biotechnology Co., Ltd. China
• Bionet-Asia Co., Ltd. Thailand