Clinical trial NCT04817917: Seroprevalence of Neutralizing Antibodies Against Japanese Encephalitis Virus Among 6 Years Old Children With 5 Different Immunization Strategies in Zhejiang Province
Official title: Seroprevalence of Neutralizing Antibodies Against Japanese Encephalitis Virus Among 6 Years Old Children With 5 Different Immunization Strategies in Zhejiang Province, China: An Open-labeled, Ambidirectional Cohort Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Japanese Encephalitis
Vaccine Preventable Disease
Vaccine Reaction
Keywords: Japanese Encephalitis
Seroprevalence
Immunogenicity
Immunization schedule
Safety
Lead sponsor: Zhejiang Provincial Center for Disease Control and Prevention
Sponsor class: OTHER_GOV
Collaborators: name: Liaoning Chengda Biotechnology CO., LTD
First posted: 2021-03-26
Enrollment: 712
Sex: ALL
Minimum age (years): 72
Maximum age (years): 75
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study is to evaluate the seroprevalence of neutralizing antibodies against Japanese encephalitis (JE) virus in children aged 6 years who were previously administered with 5 different immunization strategies by JE attenuated live vaccine (JEV-L) or/and inactivated vaccine (JEV-I). The secondary objective is to evaluate the immunogenicity of the booster dose of JEV-I at 6 years old for those previously immunized with 3 doses of JEV-I or those sequential administered with 1 dose of JEV-L and another dose of JEV-I.

Detailed description: Based on the retrospective registry in Zhejiang Provincial Immunization Information System, healthy children aged 6 years from 5 cohorts were included according to their previous immunization schedules on JE: 3 doses of JEV-I (Group 1), JEV-L+ JEV-I (Group 2), JEV-L+ JEV-I + JEV-I (Group 3), JEV-I + JEV-I+ JEV-L (Group 4), and 2 doses of JEV-L (Group 5). According to immunization programs in China, a booster dose of JEV-I is needed at the age of 6 for Group 1 and Group 2. A pre-vaccination blood sample (2.5ml) will be collected to evaluate the proportions of seropositivity before the booster dose of JEV-I. A second blood sample will be collected 28-35 days after the booster dose. Immunogenicity of the booster dose will be assessed by seroconversion rates, proportions of seropositivity and GMTs for these two groups. In addition, safety will be assessed with the occurrence of adverse events reported in these two groups. For the rest three groups who have completed the immunization schedules on JE, only one blood sample will be taken at the age of 6 to evaluate the proportions of seropositivity and GMTs after 4 years post the complete immunization schedules. Plague reduction neutralization test (PRNT) against both vaccine strains (SA-14-14-2 strain for JEV-L and Beijing P3 strain for JEV-I) will be used to test neutralizing antibody titers, so as to avoid potential bias in favor of either vaccine. PRNT50 titers (the reciprocal of the serum dilution that reduced the virus plaque count by 50% compared with the virus-only controls) ≥ 1:10 are deemed as positive.

Eligibility criteria: Inclusion Criteria:

* Participants aged ≥ 72 months to \< 75 months.
* Participants have completed routine immunization schedules in time.
* Participants are healthy native residents.
* Parents/guardians can understand the protocol requirements, provide informed consent, accept all scheduled visits, and comply with all trial procedures.

Exclusion Criteria:

* History of neurological diseases or related symptoms.
* An acute illness with fever (temperature ≥ 37.1℃) or any acute onset of chronic diseases.
* Known impairment of immunologic function, or receipt of immunosuppressive therapy or immunoglobulin in the past 3 months.
* Known allergy to any constituent of the vaccine.
* Have been injected with other vaccines or any clinical trial drugs in the past 4 weeks.
* Any condition which, in the opinion of the investigator, would pose a health risk to the subject or interfere with the vaccine.

Primary outcomes:
measure: Proportions of seropositivity of neutralizing antibodies against JE at the age of 6
timeFrame: At the age of 6. Test immediately after enrollment by a dose of blood sample.
measure: Geometric Mean Titers (GMTs) or Median antibody titers for children aged 6 years
timeFrame: At the age of 6. Test immediately after enrollment by a dose of blood sample.
Secondary outcomes:
measure: Seroconversion rates of the booster dose of JEV-I for Group 1 and Group 2
timeFrame: before and 28-35 days after the booster dose.
measure: Proportion of seropositivity of neutralizing antibodies against JE after the booster dose for Group 1 and Group 2.
timeFrame: 28-35 days after the booster dose.
measure: Geometric Mean Titers (GMTs) or Median antibody titers after the booster dose for Group 1 and Group 2.
timeFrame: 28-35 days after the booster dose.
measure: Safety of the booster dose for Group 1 and Group 2
timeFrame: From inoculation to 30 days after the inoculation.
Other outcomes:
Locations:
city: Lishui
country: China
facility: Liandu center for disease control and prevention
state: Zhejiang
city: Quzhou
country: China
facility: Kecheng center for disease control and prevention
state: Zhejiang
city: Wenzhou
country: China
facility: Pingyang center for disease control and prevention
state: Zhejiang
Study officials:
References: