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The Role of Pre-existing Cross-reactive Antibodies in Determining the Efficacy of Vaccination in Humans

NCT01943305 · Status: COMPLETED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 84

Last updated 2016-04-20

No results posted yet for this study

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.

Conditions

  • Yellow Fever
  • Encephalitis, Japanese

Interventions

BIOLOGICAL

Japanese Encephalitis vaccine

IXIARO, inactivated, adsorbed vaccine. Two doses (0.5 ml each) of IXIARO one month apart

BIOLOGICAL

Yellow Fever vaccine

STAMARIL, 1 dose (0.5 ml)

Sponsors & Collaborators

  • Duke-NUS Graduate Medical School

    collaborator OTHER

  • Singapore General Hospital

    lead OTHER

Principal Investigators

  • Jenny Low Guek Hong · Singapore General Hospital

Study Design

Allocation
RANDOMIZED
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
21 Years
Max Age
50 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2013-10-31
Primary Completion
2015-06-30
Completion
2015-12-31

Countries

  • Singapore

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01943305 on ClinicalTrials.gov