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

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.

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.

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

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

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

To evaluate the magnitude of the increase in GMTs, the GMT ratio of anti-JE neutralizing antibody titers between post-booster vaccination and pre-booster vaccination was calculated for the following:

• GMT of anti-JE neutralizing antibodies at 7 days after booster vaccination to the Year 4, pre-booster GMT of anti-JE neutralizing antibodies
• GMT of anti-JE neutralizing antibodies at 28 days after booster vaccination to the Year 4, pre-booster GMT of anti-JE neutralizing antibodies

The number of participants with at least one occurrence of an immediate reaction, including local, systemic, or unsolicited adverse event that occurred within 30 minutes of the 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.

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.

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