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2025-12-25 @ 3:27 AM
Ignite Modification Date:
2026-02-24 @ 6:12 AM
Study NCT ID:
NCT01943305
Status:
COMPLETED
Last Update Posted:
2016-04-20
First Post:
2013-09-03
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
The Role of Pre-existing Cross-reactive Antibodies in Determining the Efficacy of Vaccination in Humans
Sponsor:
Singapore General Hospital
Organization:
Study Overview
Official Title:
An Open-label Phase 2a Clinical Trial to Test the Effect of Yellow Fever Vaccination in a Background of Japanese Encephalitis Antibodies.
Status:
COMPLETED
Status Verified Date:
2016-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Epidemic viral diseases have become more prevalent in recent years. Among the various strategies to prevent such epidemics, vaccination is the most cost-effective. However, populations that are immunized are typically already exposed to multiple previous vaccinations or natural infections. Studies from this and other laboratories have revealed that pre-existing dengue antibodies can either inhibit or enhance subsequent dengue infection depending on the pre-existing antibody levels. While cross-reactive antibody is potentially pathogenic in dengue, how it impacts immune response to vaccination is unclear. Indeed, aggregated at the site of vaccination and the respective draining lymph nodes are antigen-presenting and immune regulatory cells that express Fc receptors and play pivotal roles in determining the magnitude and polarity of the immune response. Vaccine uptake by these antigen-presenting cells may thus be either inhibited or enhanced when vaccines are opsonized with cross-reactive antibodies.
In view of the limited knowledge on how cross-reactive antibodies affect vaccination outcome, investigators propose here a study that exploits the known cross reactivity between Japanese encephalitis (JE) virus antibody and yellow fever (YF) vaccine. Investigators hypothesize that cross-reactive antibodies impacts antibody response to YF at the point vaccination in a concentration-dependent manner by altering both vaccine uptake and the innate immune response by antigen presenting cells. Investigators will structure an open label clinical trial on sequential vaccination with JE and YF vaccines, with different time intervals between vaccinations. This would test immune response to YF vaccination in subjects with different titer of cross-reactive JE vaccine-derived antibodies.
In view of the limited knowledge on how cross-reactive antibodies affect vaccination outcome, investigators propose here a study that exploits the known cross reactivity between Japanese encephalitis (JE) virus antibody and yellow fever (YF) vaccine. Investigators hypothesize that cross-reactive antibodies impacts antibody response to YF at the point vaccination in a concentration-dependent manner by altering both vaccine uptake and the innate immune response by antigen presenting cells. Investigators will structure an open label clinical trial on sequential vaccination with JE and YF vaccines, with different time intervals between vaccinations. This would test immune response to YF vaccination in subjects with different titer of cross-reactive JE vaccine-derived antibodies.
Detailed Description:
The primary objective of this clinical study is to examine the role of cross-reactive antibodies in modulating immune responses to vaccines.
1. Hypothesis: Antibody response to YF vaccination is influenced by the heterologous antibody titer at the point of YF vaccination.
2. Hypothesis : Heterologous antibody to YF affect magnitude of vaccine uptake through the Fc receptors and alters the quality and magnitude of the innate immune response following YF vaccination, which has been previously shown to predictive of immune response to YF vaccination.
Secondary objectives
1. To determine neutralizing antibody response to YF vaccination in human volunteers at different time intervals following a prior JE vaccination.
2. To characterize the innate immune response to YF vaccination at different time intervals after a prior JE vaccination.
A total of 100 healthy adults, pre-screened to be negative for anti-dengue antibodies will be enrolled upon written informed consent. 75 subjects in the test arm will received 2 doses of inactivated JE vaccine(Ixiaro), while 25 subjects in the control arm has no JE vaccination.
Subjects in the test arm will be sub-divided into 3 groups who receive YF17D:
Group1.YF vaccination 1-month post-JE vaccination Group 2.YF vaccination 4-months post-JE vaccination Group 3.YF vaccination 9-months post-JE vaccination Subjects in the control arm (group 4) will receive YF vaccination at the same time as group 1.
Blood sampling in relation to YF17D vaccination:
1. Pre-dose
2. 1-day after
3. 3-days after (+ 1 day)
4. 1-week after (± 2 days)
5. 1-month after (± 5 days)
6. 1-year after (± 14 days)
Primary end-point: Difference in geometric mean titre of YF17D neutralizing antibody.
1. Hypothesis: Antibody response to YF vaccination is influenced by the heterologous antibody titer at the point of YF vaccination.
2. Hypothesis : Heterologous antibody to YF affect magnitude of vaccine uptake through the Fc receptors and alters the quality and magnitude of the innate immune response following YF vaccination, which has been previously shown to predictive of immune response to YF vaccination.
Secondary objectives
1. To determine neutralizing antibody response to YF vaccination in human volunteers at different time intervals following a prior JE vaccination.
2. To characterize the innate immune response to YF vaccination at different time intervals after a prior JE vaccination.
A total of 100 healthy adults, pre-screened to be negative for anti-dengue antibodies will be enrolled upon written informed consent. 75 subjects in the test arm will received 2 doses of inactivated JE vaccine(Ixiaro), while 25 subjects in the control arm has no JE vaccination.
Subjects in the test arm will be sub-divided into 3 groups who receive YF17D:
Group1.YF vaccination 1-month post-JE vaccination Group 2.YF vaccination 4-months post-JE vaccination Group 3.YF vaccination 9-months post-JE vaccination Subjects in the control arm (group 4) will receive YF vaccination at the same time as group 1.
Blood sampling in relation to YF17D vaccination:
1. Pre-dose
2. 1-day after
3. 3-days after (+ 1 day)
4. 1-week after (± 2 days)
5. 1-month after (± 5 days)
6. 1-year after (± 14 days)
Primary end-point: Difference in geometric mean titre of YF17D neutralizing antibody.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: