Humoral Response to Tick-borne Encephalitis Vaccine in Elderly

Sormland County Council, Sweden

Status and phase: Completed; Phase 3; Phase 2

Conditions: Tick-borne Encephalitis

Treatments: Biological: FSME-immune

Study type: Interventional

Funder types: Other

Identifiers

NCT01361776

2011/4-31/2

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 4 patient groups

TBE vaccine at 0+30 days

Active Comparator group

Description:

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

Treatment:

Biological: FSME-immune

TBE vaccine at 0+7+21 days

Active Comparator group

Description:

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

Treatment:

Biological: FSME-immune

TBE vaccinte at 0+30+90 days

Active Comparator group

Description:

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

Treatment:

Biological: FSME-immune

younger participants

Active Comparator group

Description:

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

Treatment:

Biological: FSME-immune