Ixiaro as Booster After Mouse-brain Derived Vaccines for Japanese Encephalitis

Ability of the New Vero-cell-derived Inactivated Japanese Encephalitis Vaccine (IXIARO) to Elicit a Booster Response in Travellers Previously Vaccinated With Traditional Mouse-brain Derived Vaccine (JE-MB)

The old mouse brain derived Japanese encephalitis vaccines (MBJEV) have been reported to cause serious adverse effects and are therefore replaced with the novel Ixiaro vaccine. The present study investigates whether vaccinees primed with MBJEV can be boosted with Ixiaro.

Travellers receiving Japanese encephalitis vaccines are enrolled for a follow-up of immune responses in four groups: A) primary immunization with BMJEV, B) primary and secondary immunizations with MBJEV, C) primary immunizations with Ixiaro and S) Primary immunization with MBJEV and secondary immunization with Ixiaro. Immune responses are followed with help of serum samples collected before and after vaccination.

Study Overview

• Status: Completed
• Conditions: Japanese Encephalitis
• Intervention / Treatment: Biological: Mouse brain derived japanese encephalitis vaccine (MB-JEV); Biological: Primary and booster immunizations with MB-JEV; Biological: C) primary immunizations with Ixiaro; Biological: S) Ixiaro booster to MBJEV primed

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female travellers ≥ 18 years of age.

  • General good health.
  • Written informed consent.
  • Ability to attend all visits scheduled in this study.
  • Travellers who have previously got a primary vaccination series of 2 or 3 doses of JE-MB and now receive a booster vaccination , either MB-JEV or IXIARO, at the travel clinic for their journey to Asia, OR
  • Travellers with no previous vaccination against JE who are given the primary vaccination series with IXIARO at a travel clinic prior to their journey to Asia.

Exclusion Criteria:

• - < 18 years of age.
• Acute disease at the time of enrollment.
• Pregnancy or lactation.
• Known immunodeficiency or immune suppressive treatment.
• Any chronic illness that might interfere with the immune response; history of JE.
• Alcohol or drug abuse.
• Any clinically significant history of known or suspected anaphylaxis or hypersensitivity (based on the investigator's judgement).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A) primary immunization with MB-JEV; Volunteers immunized with MB-JEV	Biological: Mouse brain derived japanese encephalitis vaccine (MB-JEV); a) 2-3 doses of MB-JEV vaccine 0.5ml given on day 0, 7, 30 immunization and one booster dose of Ixiaro 0.5 ml > 2 years later; Other Names: Korean Green Cross
Active Comparator: Primary and booster MBJEV vaccinations; Booster immunization with MB-JEV of vaccinees primed with MB-JEV	Biological: Primary and booster immunizations with MB-JEV; 2-3 doses of MB-JEV vaccine 0.5ml given on day 0, 7, 30 as primary immunization and one booster dose of 0.5 ml > 2 years later; Other Names: Korean Green Cross
Active Comparator: C) primary immunizations with Ixiaro; Primary immunization with Ixiaro 2 dose	Biological: C) primary immunizations with Ixiaro; 2 0.5 ml doses of Ixiaro 28 days apart; Other Names: Ixiaro
Active Comparator: S) Ixiaro booster to MBJEV primed; Actual study group:Booster immunization with Ixiaro to those primed previously with MB-JEV	Biological: S) Ixiaro booster to MBJEV primed; 0.5ml Ixiaro to volunteers previously primed with 2-3 doses of MB-JEV; Other Names: Ixiaro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibody titers 1 month after last vaccine dose	Determination of antibody titers 1 month after last vaccine dose	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibody titers two years after vaccination	Measurement of antibody titers two years after vaccination	2 years

Collaborators and Investigators

• Sponsor: Helsinki University Central Hospital
• Collaborators: Karolinska Institutet
• Investigators: Principal Investigator: Elina Erra, MD, Haartman Institute, University of Helsinki; Principal Investigator: Lars Lindqvist, MD PhD, Department of infectious diseases Stockholm, Sweden; Principal Investigator: Eili Huhtamo, PhD, Haartman Institute, University of Helsinki; Principal Investigator: Olli Vapalahti, MD PhD, Haartman Institute, University of Helsinki; Principal Investigator: Sari Pakkanen, MSc, Haartman Institute, University of Helsinki; Principal Investigator: Sirkka Vene, BMA, Swedish Institute of Infectious Disease Control; Principal Investigator: Jukka Riutta, MD, Travel clinic, Postitalo, Lääkärikeskus; Study Director: Anu Kantele, MD PhD, Helsinki University Central Hospital; Study Director: Lars Rombo, MD PhD, Karolinska Institutet

Publications and helpful links

General Publications

• Erra EO, Askling HH, Rombo L, Riutta J, Vene S, Yoksan S, Lindquist L, Pakkanen SH, Huhtamo E, Vapalahti O, Kantele A. A single dose of vero cell-derived Japanese encephalitis (JE) vaccine (Ixiaro) effectively boosts immunity in travelers primed with mouse brain-derived JE vaccines. Clin Infect Dis. 2012 Sep;55(6):825-34. doi: 10.1093/cid/cis542. Epub 2012 Jun 13.

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: June 30, 2011
• First Submitted That Met QC Criteria: June 30, 2011
• First Posted (Estimate): July 1, 2011

Study Record Updates

• Last Update Posted (Estimate): October 28, 2011
• Last Update Submitted That Met QC Criteria: October 27, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: Ixiaro; japanese encephalitis vaccine; booster
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Encephalitis, Japanese; Encephalitis
• Other Study ID Numbers: 382/E7/07