Humoral Response to Tick-borne Encephalitis Vaccine in Elderly

Humoral Response to TBE Vaccine in Elderly (50+ Year Olds) After Changed Dosage Intervals/Number of Doses?

Antibody titers after tick-borne encephalitis (TBE) vaccination are less in elderly and vaccination breakthroughs are more common in this age group. This has prompted Swedish authorities to recommend an additional dose in the initial vaccination schedule (= 0+30+90 days instead of the usually recommended 0+30 days. The investigators intend to evaluate this regime.

Study Overview

• Status: Completed
• Conditions: Tick-borne Encephalitis
• Intervention / Treatment: Biological: FSME-immune

Detailed Description

The risk for TBE increases in Sweden. Together with an increased awareness of the possibility to acquire protection by vaccination, this has led to an increase in the number of doses of the vaccine distributed in Sweden each year -now being approximately 400.000. The first year, two doses with an interval of 1 month is recommended for the general population, followed by a third dose approximately one year later and an additional booster dose three years after the third.

Recent studies show that the antibody titers against TBE are substantially less in an older population. This is in line with the present recommendation from Austria that booster intervals should be shortened to 3 years in the age group 60+. It is also in line with a report of vaccination failures where 13/27 patients were older than 60 years According to a study by Jilkowa et al, 18 % (38/185) in the age group 60+ did not achieve putative levels of antibody titers after the first two doses. Therefore, the manufacturer of Encepur recommends a total of three doses to this age group using the same regimen as with "accelerated vaccination schedule (0+7+21 days). Unfortunately, GMT (geometrical mean of titers) after 3 doses with the accelerated schedule are not superior to 2 doses given at 0+30 days.

The manufacturer of FSME-immun instead recommends that serology should be checked one month after the second dose and that a third dose should be given if titers are not sufficient (0+30+60 days). Unfortunately, determinations of titers in a large number of samples put severe strain on logistics and is not feasible in Sweden.

In order to try to improve immunity in the age group 60+ , the Department of Communicable Disease Control and Prevention in Stockholm therefore recommends a third dose two months after the first two doses to the age group 60+ (0+30+60 days).

Study design. The investigators intend to give FSME-immune to 3 groups with varying vaccination schedules ( 0+7+21, 0+30 or 0+30+90. 50 participants will be randomized to each group. Half of them will be between 50-59 years and half will be at least 60 years old. A younger age group (50 participants between 18-49 years) will serve as controls and will be given FSME-immune according to standard recommendations (0+30 days).

Serum samples (10 ml of blood) will be obtained at five times: 0,60,120,360 and 400 days after first dose Samples will be analysed for neutralising antibodies at the Swedish institute for Infectious disease control - other options possible.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Finland
  • Helsingfors, Finland, 00029
    • Dept infectious diseases
• Sweden
  • Eskilstuna, Sweden, 631 88
    • Dept infectious diseases
  • Karlstad, Sweden, 651 85
    • Dept infectious diseases
  • Stockholm, Sweden, 17176
    • Department of Infectious Diseases
  • Uppsala, Sweden, 751 85
    • Dept infectious diseases
  • Örebro, Sweden
    • Department of Infectious Diseases

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 50 years or more
• generally healthy
• no immunosuppressive condition
• fertile women must use contraceptives

Exclusion Criteria:

• Previous TBE infection
• Previously immunized with TBE vaccine
• Anaphylactic reaction to egg protein
• Any disease or therapy which might suppress the immune response
• Vaccination should be delayed if a participant has fever

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: TBE vaccine at 0+30 days; This group of 50 participants will follow the standard recommendation and will be given TBE vaccine 0.5 ml FSME immune at 0 + 30 days during the first year and an additional dose one year later	Biological: FSME-immune; 0.5 ml im as scheduled in the 4 arms
Active Comparator: TBE vaccine at 0+7+21 days; This group of 50 participants will will be given TBE vaccine 0.5 ml FSME immune at 0 + 7 +21 days during the first year and an additional dose one year later	Biological: FSME-immune; 0.5 ml im as scheduled in the 4 arms
Active Comparator: younger participants; This group of 50 participants in the age group 18-49 years will be given TBE vaccine 0.5 ml FSME immune at 0 +30 days during the first year and an additional dose one year later	Biological: FSME-immune; 0.5 ml im as scheduled in the 4 arms
Active Comparator: TBE vaccinte at 0+30+90 days; This group of 50 participants will will be given TBE vaccine 0.5 ml FSME immune at 0 + 30 + 90 days during the first year and an additional dose one year later	Biological: FSME-immune; 0.5 ml im as scheduled in the 4 arms

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum concentration of neutralising antibodies against TBE one month after two or three doses.	Determination of neutralising antibodies one month after completion of the first years vaccination series	18 months after the first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum concentration of neutralising antibodies against TBE one month after the dose which will be given a year later	Determination of neutralising antibodies one month after the dose which will be given a year later	18 months after the first dose has been given

Collaborators and Investigators

• Sponsor: Sormland County Council, Sweden

Publications and helpful links

General Publications

• Kantele A, Rombo L, Vene S, Kundi M, Lindquist L, Erra EO. Three-dose versus four-dose primary schedules for tick-borne encephalitis (TBE) vaccine FSME-immun for those aged 50 years or older: A single-centre, open-label, randomized controlled trial. Vaccine. 2022 Feb 23;40(9):1299-1305. doi: 10.1016/j.vaccine.2022.01.022. Epub 2022 Jan 31.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: May 25, 2011
• First Submitted That Met QC Criteria: May 26, 2011
• First Posted (Estimate): May 27, 2011

Study Record Updates

• Last Update Posted (Estimate): November 18, 2015
• Last Update Submitted That Met QC Criteria: November 17, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: elderly; immune response; TBE-vaccine; additional doses
• 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; Tick-Borne Diseases; Encephalitis; Encephalitis, Tick-Borne
• Other Study ID Numbers: 2011/4-31/2