Immunogenicity, Safety, and Antibody Persistence of Different Immunization Strategies Against Japanese Encephalitis

The main objective of this study is to evaluate the persistence of Japanese encephalitis antibodies in participants at the age of 6, after they have followed different Japanese encephalitis vaccination schedules. Furthermore, the study will assess the immunogenicity and antibody persistence of primary immunization across different Japanese encephalitis vaccination schedules, as well as the immunogenicity following booster immunizations within these schedules. The safety of each vaccine dose will also be evaluated.

Study Overview

• Status: Active, not recruiting
• Conditions: Japanese Encephalitis Vaccine
• Intervention / Treatment: Biological: Japanese Encephalitis Vaccine (Vero Cell), Inactivated; Biological: Japanese Encephalitis Vaccine, Live

Detailed Description

This is a randomized, controlled, open-label, non-inferiority study. Healthy children aged 8 months will be invited to participate and randomly allocated to six groups (Group 1 to Group 6) in a 1:1:1:1:1:1 ratio. They will be administered the inactivated Japanese encephalitis vaccine (JEV-I) and/or the live attenuated Japanese encephalitis vaccine (JEV-L) based on the six schedules delineated in the protocol. The primary immunization will be administered to participants at 8 months of age, and a booster dose will be given at 24 months of age. Additionally, participants in Groups 1, 2, and 5 will receive an additional booster dose at the age of 6.

Blood samples (3 mL) will be collected from participants at 8 months, 24 months, and 6 years of age. Samples will be taken before vaccination and 30 days after it for detecting Japanese encephalitis neutralizing antibodies. The titers of these antibodies will be assayed via the 50% plaque reduction neutralization test. Those in groups 3, 4, and 6 who've completed all immunization procedures by 24 months old will have a blood sample taken at 6 years old.

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Jiaxing, Zhejiang, China
      • Jiashan County Center for Disease Control and Prevention
    • Jiaxing, Zhejiang, China
      • Pinghu Center For Disease Control and Prevention
    • Jinhua, Zhejiang, China
      • Dongyang Center for Disease Control and Prevention
    • Jinhua, Zhejiang, China
      • Yongkang Center for Disease Control and Prevention
    • Ningbo, Zhejiang, China
      • Yuyao Center for Disease Control and Prevention
    • Quzhou, Zhejiang, China
      • Jiangshan Center For Disease Control and Prevention

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy children aged 8 months who are permanent residents of the study area.
• Legal guardians can understand the requirements and processes of the study, provide written informed consent, and comply with all procedures as required by the clinical research protocol.
• Able to receive the full course of Japanese encephalitis vaccinations according to the immunization strategy in the research protocol, including receiving the primary immunization at 8 months of age and the booster immunizations at 24 months of age and 6 years of age.

Exclusion Criteria:

• Unable to finish the full course of primary and booster immunizations at the study area, and unable to fulfill the follow-up visits prescribed in the protocol.
• Non-compliance with the vaccination strategy for each group, as stated in the protocol, regarding Japanese encephalitis vaccines with proper doses and varieties.
• Allergic to any component of the study vaccine or having a history of allergic reactions to any vaccines.
• Having a history of symptoms or signs of neurological diseases or other contraindications for Japanese encephalitis vaccine vaccination.
• Having used immunosuppressants or blood products following birth.
• Receiving other vaccines simultaneously while receiving the Japanese encephalitis vaccine of this project.
• Any conditions that may interfere with the evaluation of the study, as deemed by the researcher.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 (4 doses of JEV-I); Participants will receive 2 doses of JEV-I (7-10 days apart) at 8 months of age, 1 dose of JEV-I at 24 months of age, and 1 dose of JEV-I at 6 years of age.	Biological: Japanese Encephalitis Vaccine (Vero Cell), Inactivated; 0.5ml for each dose, manufactured by Liaoning Chengda Biotechnology Co., Ltd., administered in the deltoid area of lateral arm by intramuscular injection.
Experimental: Group 2 (4 doses of JEV-I); Participants will receive 2 doses of JEV-I (28-35 days apart) at 8 months of age, 1 dose of JEV-I at 24 months of age, and 1 dose of JEV-I at 6 years of age.	Biological: Japanese Encephalitis Vaccine (Vero Cell), Inactivated; 0.5ml for each dose, manufactured by Liaoning Chengda Biotechnology Co., Ltd., administered in the deltoid area of lateral arm by intramuscular injection.
Experimental: Group 3 (2 doses of JEV-I and 1 dose of JEV-L); Participants will receive 2 doses of JEV-I (7-10 days apart) at 8 months of age and 1 dose of JEV-L at 24 months of age.	Biological: Japanese Encephalitis Vaccine (Vero Cell), Inactivated; 0.5ml for each dose, manufactured by Liaoning Chengda Biotechnology Co., Ltd., administered in the deltoid area of lateral arm by intramuscular injection.; Biological: Japanese Encephalitis Vaccine, Live; 0.5ml for each dose, manufactured by Chengdu Institute of Biological Products Co., Ltd., administered subcutaneously in the lower part of the deltoid area of lateral arm.
Experimental: Group 4 (1 dose of JEV-L and 2 doses of JEV-I); Participants will receive 1 dose of JEV-L at 8 months of age and 2 doses of JEV-I (7-10 days apart) at 24 months of age.	Biological: Japanese Encephalitis Vaccine (Vero Cell), Inactivated; 0.5ml for each dose, manufactured by Liaoning Chengda Biotechnology Co., Ltd., administered in the deltoid area of lateral arm by intramuscular injection.; Biological: Japanese Encephalitis Vaccine, Live; 0.5ml for each dose, manufactured by Chengdu Institute of Biological Products Co., Ltd., administered subcutaneously in the lower part of the deltoid area of lateral arm.
Experimental: Group 5 (1 dose of JEV-L and 2 doses of JEV-I); Participants will receive 1 dose of JEV-L at 8 months of age, 1 dose of JEV-I at 24 months of age, and 1 dose of JEV-I at 6 years of age.	Biological: Japanese Encephalitis Vaccine (Vero Cell), Inactivated; 0.5ml for each dose, manufactured by Liaoning Chengda Biotechnology Co., Ltd., administered in the deltoid area of lateral arm by intramuscular injection.; Biological: Japanese Encephalitis Vaccine, Live; 0.5ml for each dose, manufactured by Chengdu Institute of Biological Products Co., Ltd., administered subcutaneously in the lower part of the deltoid area of lateral arm.
Active Comparator: Group 6 (2 doses of JEV-L); Participants will receive 2 doses of JEV-L at 8 months of age, and 1 dose of JEV-L at 24 months of age.	Biological: Japanese Encephalitis Vaccine, Live; 0.5ml for each dose, manufactured by Chengdu Institute of Biological Products Co., Ltd., administered subcutaneously in the lower part of the deltoid area of lateral arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Testing Seropositive for Japanese Encephalitis Neutralizing Antibodies	The persistence of immunity following various Japanese encephalitis (JE) vaccination schedules is evaluated based on the proportion of participants exhibiting seropositivity for JE neutralizing antibodies at 6 years of age. Seropositivity is defined as a JE neutralizing antibody titer of at least 1:10, as ascertained by the 50% plaque reduction neutralization test.	4 years after the booster vaccination at 24 months of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroconversion Rates of Japanese Encephalitis Neutralizing Antibodies after Primary vaccination	The seroconversion rate is defined as the percentage of participants with a change in Japanese Encephalitis neutralizing antibody titer from <1:10 at baseline (pre-vaccination) to a titer of ≥1:10 30 days post-vaccination, or a 4-fold or greater rise from the baseline, as measured by the 50% plaque reduction neutralization test	30 days post-primary immunization
Geometric Mean Titer of Japanese Encephalitis Neutralizing Antibodies before and after Primary Immunization		pre-primary immunization (Day 0) and 30 days post-primary immunization
Percentage of Participants Testing Seropositive for Japanese Encephalitis Neutralizing Antibodies before and after Primary Immunization	Seropositivity is defined as a Japanese Encephalitis neutralizing antibody titer of at least 1:10, as ascertained by the 50% plaque reduction neutralization test.	pre-primary immunization (Day 0) and 30 days post-primary immunization
Seroconversion Rates of Japanese Encephalitis Neutralizing Antibodies after Booster vaccination	The seroconversion rate is defined as the percentage of participants with a change in Japanese Encephalitis neutralizing antibody titer from <1:10 at baseline (pre-vaccination) to a titer of ≥1:10 30 days post-vaccination, or a 4-fold or greater rise from the baseline, as measured by the 50% plaque reduction neutralization test	30 days post-booster immunization
Geometric Mean Titer of Japanese Encephalitis Neutralizing Antibodies before and after booster Immunization		pre-booster immunization (Day 0) and 30 days post-booster immunization
Percentage of Participants Testing Seropositive for Japanese Encephalitis Neutralizing Antibodies before and after booster Immunization	Seropositivity is defined as a Japanese Encephalitis neutralizing antibody titer of at least 1:10, as ascertained by the 50% plaque reduction neutralization test.	pre-booster immunization (Day 0) and 30 days post-booster immunization
Incidence of any Local and Systemic Adverse Events Within 30 Days of Each Vaccination	Adverse events will be collected through a combination of proactive visits by researchers and participant reports	within 30 days of each vaccination

Collaborators and Investigators

• Sponsor: Liaoning Chengda Biotechnology CO., LTD
• Collaborators: Zhejiang Provincial Center for Disease Control and Prevention
• Investigators: Study Director: Huanyu Wang, Liaoning Chengda Biotechnology CO., LTD

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2023
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: February 9, 2025
• First Submitted That Met QC Criteria: February 9, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infectious Encephalitis; Vector Borne Diseases; Neuroinflammatory Diseases; Mosquito-Borne Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; RNA Virus Infections; Virus Diseases; Arbovirus Infections; Flavivirus Infections; Flaviviridae Infections; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Encephalitis, Arbovirus; Encephalitis; Encephalitis, Japanese; Immunologic Factors; Physiological Effects of Drugs; Vaccines
• Other Study ID Numbers: CDB-JE-PM-2023002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No