Long-term Immunogenicity After Receipt of JE Vaccine and Antibody Response and Safety to a Booster Dose

PATH561 enrolled

Overview

This study aims to understand the persistence of the Japanese encephalitis (JE) antibody response in previously vaccinated children. The proposed study will enrol Bangladeshi children who had previously participated in a lot to lot consistency study (JEV05; NCT01567865) of JE live attenuated SA 14-14-2 vaccine (CD-JEV).

Study participants previously immunized with CD-JEV (Clinical Trials identifier: NCT01567865, JEV05) will have serum collected three and four years after initial vaccination to assess long-term immunogenicity. Four years after receiving the initial dose of CD-JEV, eligible participants will be vaccinated with a second subcutaneous dose of CD-JEV to assess the antibody response. Participants will be monitored for safety for 28 days following receipt of the booster dose.

Study Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

561

Conditions

Encephalitis, Japanese

Interventions

Live Attenuated Japanese Encephalitis SA-14-14-2 VaccineBIOLOGICAL

0.5 mL subcutaneous injection

Eligibility

Sex: ALLMin age: 43 MonthsMax age: 51 MonthsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Participant in JEV05 study (NCT01567865) and received one dose of CD-JEV. * Resides in the Matlab or Mirpur study area. * At least one parent or guardian willing to provide written informed consent. Exclusion Criteria: * Received a second dose of Japanese encephalitis vaccine within the past three years. * Received immunoglobulins and/or any blood products within 90 days prior to enrollment. * Been diagnosed with a primary or acquired immunodeficiency, including human immunodeficiency virus (HIV) infection within the past three years.

Outcomes

Primary Outcomes

Seroprotection Rate Three and Four Years After Initial Vaccination With CD-JEV

Seroprotection rate is defined as the percentage of participants with an anti-Japanese encephalitis (JE) neutralizing antibody titer ≥ 1:10 as measured using a 50% plaque reduction neutralization test (PRNT-50). Seroprotection was assessed at 3 and 4 years after the initial vaccination in Study JEV05, prior to participants receiving a booster vaccination in the current study.

Time frame: 3 years after initial vaccination (Study Day 1) and 4 years after initial vaccination (Study Day 365)

Geometric Mean Titer of Anti-JE Neutralizing Antibodies Three and Four Years After Initial Vaccination With CD-JEV

The geometric mean titer (GMT) of anti-JE neutralizing antibodies 3 and 4 years after initial vaccination with CD-JEV in Study JEV05 and prior to receiving the booster vaccination in the current study, measured using PRNT-50.

Time frame: 3 years after initial vaccination (Study Day 1) and 4 years after initial vaccination (Study Day 365)

Secondary Outcomes

Seroprotection Rate 7 Days and 28 Days After Booster Dose

Seroprotection rate is defined as the percentage of study participants with an anti-JE neutralizing antibody titer ≥1:10 assessed using PRNT-50.

Time frame: 7 days and 28 days following booster vaccination (Study Days 372 and 393)

GMT of Anti-JE Neutralizing Antibodies 7 Days and 28 Days After Booster Dose

Geometric mean titer of anti-JE neutralizing antibodies measured using PRNT-50.

Time frame: 7 days and 28 days following booster vaccination (Study Days 372 and 393)

Seroconversion Rate 7 Days and 28 Days After Booster Dose

Seroconversion rate is defined as the percentage of study participants with either: * For participants who were seronegative at Baseline (defined as anti-JE neutralizing antibody titer of \< 1:10 assessed using PRNT-50 at Year 4, prior to booster vaccination): A change in serostatus from seronegative (anti-JE neutralizing antibody titer of \< 1:10) to positive (anti-JE neutralizing antibody titer ≥ 1:10) * For participants who were seropositive at Baseline (defined as an anti-JE neutralizing antibody titer ≥1:10 assessed using PRNT-50 at Year 4, prior to booster vaccination): a 4-fold increase in anti-JE neutralizing antibody titer relative to Baseline anti-JE neutralizing antibody titer

Data from ClinicalTrials.gov

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Number of Participants With Solicited Local Reactions Occurring Within 7 Days of Booster Vaccination

Participants were monitored for local reactions from 30 minutes through 7 days post booster vaccination. Local reactions (at the injection site) included the following: * Ecchymosis (bruising) * Erythema (redness) * Edema (swelling) * Induration (hardness) * Pain/tenderness Local ecchymosis, erythema, edema, and induration were graded as follows: * Grade 1: ≤ 2.5 cm in diameter * Grade 2: \> 2.5 cm in diameter with \< 50% surface area of extremity involved * Grade 3: ≥ 50% surface area of extremity involved OR ulceration OR secondary infection OR phlebitis OR sterile abscess OR drainage * Grade 4: potentially life-threatening consequences Injection site pain/tenderness were graded as follows: * Grade 1: causing no or minimal limitation in use of limb * Grade 2: causing greater than minimal limitation of use of limb * Grade 3: causing inability to perform usual social or functional activities * Grade 4: inability to perform basic self-care OR hospitalization indicated.

Time frame: From 30 minutes to 7 days following booster vaccination (Study Day 365 to 372)

Number of Participants With Solicited Systemic Reactions Occurring Within 7 Days of Booster Vaccination

Participants were monitored for systemic reactions from 30 minutes through 7 days post booster vaccination. Systemic reactions (general signs / symptoms) included the following: * Fever * Change in eating habits * Diarrhea * Sleepiness * Irritability * Unusual crying * Vomiting Fever was graded as follows: * Grade 1: 37.5 ℃ to 37.9 ℃ * Grade 2: 38.0 ℃ to 38.4 ℃ * Grade 3: 38.5 ℃ to 40.0 ℃ * Grade 4: \> 40.0 ℃ Change in eating habits, diarrhea, sleepiness, irritability, unusual crying, vomiting were graded as follows: * Grade 1: causing no or minimal interference with usual social or functional activities * Grade 2: causing greater than minimal interference with usual social or functional activities * Grade 3: causing inability to perform usual social or functional activities OR hospitalization indicated * Grade 4: inability to perform basic self-care OR medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death.

Time frame: From 30 minutes to 7 days following booster vaccination (Study Day 365 to 372)

Number of Participants With Unsolicited Adverse Events (AEs) and Serious Adverse Events (SAEs) Within 28 Days Following Booster Vaccination

AEs were graded for severity according to the following: Grade 1 (Mild): Symptoms causing no or minimal interference with usual social and functional activities Grade 2 (Moderate): Symptoms causing greater than minimal interference with usual social and functional activities Grade 3 (Severe): Symptoms causing inability to perform usual social and functional activities with intervention or hospitalization indicated Grade 4 (Potentially life-threatening): Symptoms causing inability to perform basic self-care functions OR medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. Relationship to study vaccine was based on the Clinician's assessment. A serious adverse event is defined as an AE that meets 1 of the following criteria: * Death * Life-threatening * Requires hospitalization or prolongation of existing hospitalization * Results in persistent disability * Important medical event based on medical judgement

Time frame: 28 days following booster vaccination (Study Days 365 to 393)