Japanese Encephalitis, Japanese Encephalitis Vaccine
Conditions
Keywords
Japanese encephalitis, Japanese encephalitis vaccine, T lymphocyte, Immune response
Brief summary
Japanese encephalitis (JE) live attenuated vaccine SA14-14-2 has been in use for more more than 20 years in Asia. JE vaccine SA14-14-2 is licensed in India and has been widely used since 2006. JE vaccines give protection by generating a neutralizing antibody response, but both naturally exposed persons and patients with JE also have T cell responses. Whether JE vaccine SA14-14-2 elicits T cell responses is unknown. This study tests the hypothesis that T cell responses are generated in response to JE SA14-14-2 vaccination. The aim of this study is to characterize T cell responses to JE vaccine SA14-14-2 in healthy people, and to investigate differences in T cell responses between natural exposure, vaccination and disease.
Interventions
BIOLOGICALLive attenuated Japanese encephalitis vaccine SA14-14-2
Live attenuated Japanese encephalitis vaccine SA14-14-2
Sponsors
National Institute of Mental Health and Neuro Sciences, India
University of Liverpool
PATH
Wellcome Trust
Indian Institute of Science
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* A male or female adult between 18 and 50 years of age. * Written informed consent. * Free of obvious health problems as established by medical history and history- directed physical examination before entering the study. * Expected continuous residence in India during study period, without travel outside India * An efficacious method of contraception must be used during the study for women of childbearing potential.
Exclusion criteria
* Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 days preceding administration of SA14-14-2 vaccine, or planned use during the study period. * Chronic administration of immunosuppressants or other immune-modifying drugs within a period of six months before vaccination or at any time during the study period. * Any confirmed or suspected immunosuppressive or immunodeficient condition. * A family history of congenital or hereditary immunodeficiency. * Any antiviral drug therapy within a period of six months before vaccination or at any time during the study period. * History of significant allergic disease or reactions likely to be exacerbated by any component of the study vaccine, especially allergic disease or reactions to any previous dose of any vaccine. * History of having received JE vaccine, yellow fever vaccine, tick-borne encephalitis vaccine or experimental flavivirus vaccine. * History of documented JE infection. * Detectable anti JE or West Nile neutralizing antibodies in screening tests. * Acute disease at the time of enrollment. Entry into the study may be deferred until the illness is resolved. * Acute or chronic, clinically significant, pulmonary, cardiovascular, hepatic, neurological or renal functional abnormality, as determined by history and physical or laboratory examination that is not controlled by drugs. * Administration of immunoglobulins and/or any blood products within the three months preceding administration of vaccine, or planned administration during the study period. * Seropositive for HIV, HCV or HbsAg. * Lactation, pregnancy or intention to get pregnant. * History of excessive alcohol consumption, drug abuse or significant psychiatric illness. * Any other condition that in the opinion of the investigator would pose a health risk to the participant or interfere with the evaluation of the vaccine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of T Lymphocyte Responses to Live Attenuated JE SA-14-14-2 Vaccine at Week 2. | Week 1, week 2, week 4, week 8, 6 months | Interferon gamma (IFNγ) spot forming cells (SFC)/million peripheral blood mononuclear cells (PBMC) at week 2 (peak response) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neutralizing Antibody Titres to Live Attenuated JE SA-14-14-2 Vaccine at Week 4 Post Vaccination. | 4 weeks | Neutralizing antibody titres (measured by 50% Plaque reduction neutralisation titre (PRNT50)) at 4 weeks post vaccination |
| Number of Participants Reporting Adverse Events (Graded in Severity 1-4). | one month | — |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vaccine Single dose live attenuated Japanese encephalitis vaccine SA14-14-2
Live attenuated Japanese encephalitis vaccine SA14-14-2: Live attenuated Japanese encephalitis vaccine SA14-14-2 | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Vaccine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Age, Continuous | 25 years |
| Region of Enrollment India | 17 Count of participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 17 |
| serious Total, serious adverse events | 0 / 17 |
Outcome results
Primary
Change of T Lymphocyte Responses to Live Attenuated JE SA-14-14-2 Vaccine at Week 2.
Interferon gamma (IFNγ) spot forming cells (SFC)/million peripheral blood mononuclear cells (PBMC) at week 2 (peak response)
Time frame: Week 1, week 2, week 4, week 8, 6 months
Population: 15 participants had data available at the two week time point. 1 withdrew beforehand, 1 declined to donate thew two week blood sample.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Vaccine | Change of T Lymphocyte Responses to Live Attenuated JE SA-14-14-2 Vaccine at Week 2. | 34 IFNγ SFC/million PBMC |
Secondary
Neutralizing Antibody Titres to Live Attenuated JE SA-14-14-2 Vaccine at Week 4 Post Vaccination.
Neutralizing antibody titres (measured by 50% Plaque reduction neutralisation titre (PRNT50)) at 4 weeks post vaccination
Time frame: 4 weeks
Population: 1 participant withdrew before the 4 week time point, for another the sample was not available for analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Vaccine | Neutralizing Antibody Titres to Live Attenuated JE SA-14-14-2 Vaccine at Week 4 Post Vaccination. | 18.5 Neutralising antibody titres |
Secondary
Number of Participants Reporting Adverse Events (Graded in Severity 1-4).
Time frame: one month
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vaccine | Number of Participants Reporting Adverse Events (Graded in Severity 1-4). | 3 Participants |