Primary TBE Vaccination for the Elderly

NCT04573205 | Unknown Phase 4 DMC

• 1 other identifier: O2019-1
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

Tick-borne Encephalitis (TBE) can be prevented by vaccine. Vaccine failure, defined as a case of TBE regardless of previous vaccination, has been described and seems to be more predominant with increasing age, suggesting a less effective immune response following with increasing age. In fact previous studies has shown a reduced antibody response in elderly individuals compared to younger when vaccinated against TBE. As a result, in Sweden, an extra vaccine dose has been recommended during the primary vaccine schedule to individuals \> 50 years of age. This alternative vaccine schedule has not been tested. The investigator aim to test if an extra vaccine dose in the primary vaccine schedule for those \> 50 years of age improves the immune response and offers a corresponding immunity to younger individuals following TBE vaccination.

Conditions

Tick-borne Encephalitis; Vaccine

Keywords

Elderly; Tick-borne Encephalitis; Vaccine

Outcome Measures

Primary Outcomes (2)

• Serological response to vaccination with TBE vaccine following primary vaccination

  The proportion of individuals \> 50 years that achieves protective levels following the extra primary vaccine dose compared to the proportion of individuals tha achieve protective levels of neutralizing antibodies following the second vaccine dose in those \< 40 years.

  NT measured 1 months after vaccination

• Serological response to vaccination with TBE vaccine following the full vaccine scehdule

  The proportion of individuals \> 50 years that achieves protective levels of neutralizing antibodies following the final primary schedule ( dose 4), compared to those \< 40 years ( 3 doses).

  NT measured 1 months after vaccination

Secondary Outcomes (2)

• Cellular immunity in young and elderly ( immune cell expression)

  Measured 7 days after vaccination

• Cellular immunity in young and elderly ( cytokine production)

  Measured 7 days after vaccination

Study Arms (2)

> 50 years

EXPERIMENTAL

Healthy individuals \> 50 years of age divided into age groups 50-59 years, 60-69 years and \>70 years, approximately 20 participants in each group. Vaccinated with 4 doses FSME immune Adult intramuscular injection according to the recommended primary vaccine Schedule in Sweden for individuals \> 50 years of age, at time 0, 1, 2 and 7 months.

Drug: FSME-IMMUN Vaccine

< 40 years

ACTIVE COMPARATOR

Healthy individuals \< 40 years of age. Vaccinated with 3 doses FSME immune Adult intramuscular injection according to the standard recommended primary vaccine at time 0, 1, and 7 months.

Drug: FSME-IMMUN Vaccine

Interventions

FSME-IMMUN Vaccine DRUG

0.5 ml intramuscular injection scheduled in the two different arms

< 40 years; > 50 years

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥ 50 years or between 18-40 years
• Man or woman
• God health
• Written informed consent

You may not qualify if:

• Previous vaccination against TBE
• Previous TBE infection
• Allergy or hypersensitivity to any substance in the vaccine
• Previously known or suspected infection with Japanese encephalitis, Dengue virus, West Nile fever or Yellow fever
• Information on previous vaccination against Yellow fever or Japanese encephalitis
• Acute illness, eg fever with malaise
• Immunosuppression, due to medication or disease
• Previous treatment with Rituximab or equivalent
• Autoimmune disease, including diabetes (diet or tablet-treated diabetes with good metabolic control is accepted, HbA1c \< 6 %)
• Obesity, BMI \> 40
• Moderate to severe renal failure including hemodialysis, estimated GFR \< 30.
• Blood transfusion or immunoglobulins \<3 months ago
• Pregnancy
• Any other illness where the investigator consider the subject unsuitable for the study
• The study subject does not want to participate

Sponsors & Collaborators

• Region Örebro County: lead

Study Sites (1)

Region Örebro Län

Örebro, 70185, Sweden

Location

Related Publications (15)

• Lindquist L, Vapalahti O. Tick-borne encephalitis. Lancet. 2008 May 31;371(9627):1861-71. doi: 10.1016/S0140-6736(08)60800-4.

  PMID: 18514730 BACKGROUND

• Prymula R, Pollabauer EM, Pavlova BG, Low-Baselli A, Fritsch S, Angermayr R, Geisberger A, Barrett PN, Ehrlich HJ. Antibody persistence after two vaccinations with either FSME-IMMUN(R) Junior or ENCEPUR(R) Children followed by third vaccination with FSME-IMMUN(R) Junior. Hum Vaccin Immunother. 2012 Jun;8(6):736-42. doi: 10.4161/hv.20058. Epub 2012 Jun 1.

  PMID: 22699436 BACKGROUND

• Jilkova E, Vejvalkova P, Stiborova I, Skorkovsky J, Kral V. Serological response to tick-borne encephalitis (TBE) vaccination in the elderly--results from an observational study. Expert Opin Biol Ther. 2009 Jul;9(7):797-803. doi: 10.1517/14712590903066711.

  PMID: 19527104 BACKGROUND

• Hainz U, Jenewein B, Asch E, Pfeiffer KP, Berger P, Grubeck-Loebenstein B. Insufficient protection for healthy elderly adults by tetanus and TBE vaccines. Vaccine. 2005 May 9;23(25):3232-5. doi: 10.1016/j.vaccine.2005.01.085.

  PMID: 15837226 BACKGROUND

• Hansson KE, Rosdahl A, Insulander M, Vene S, Lindquist L, Gredmark-Russ S, Askling HH. Tick-borne Encephalitis Vaccine Failures: A 10-year Retrospective Study Supporting the Rationale for Adding an Extra Priming Dose in Individuals Starting at Age 50 Years. Clin Infect Dis. 2020 Jan 2;70(2):245-251. doi: 10.1093/cid/ciz176.

  PMID: 30843030 BACKGROUND

• Lindblom P, Wilhelmsson P, Fryland L, Matussek A, Haglund M, Sjowall J, Vene S, Nyman D, Forsberg P, Lindgren PE. Factors determining immunological response to vaccination against tick-borne encephalitis virus in older individuals. PLoS One. 2014 Jun 26;9(6):e100860. doi: 10.1371/journal.pone.0100860. eCollection 2014.

  PMID: 24967619 BACKGROUND

• Stiasny K, Aberle JH, Keller M, Grubeck-Loebenstein B, Heinz FX. Age affects quantity but not quality of antibody responses after vaccination with an inactivated flavivirus vaccine against tick-borne encephalitis. PLoS One. 2012;7(3):e34145. doi: 10.1371/journal.pone.0034145. Epub 2012 Mar 26.

  PMID: 22461903 BACKGROUND

• Weinberger B, Keller M, Fischer KH, Stiasny K, Neuner C, Heinz FX, Grubeck-Loebenstein B. Decreased antibody titers and booster responses in tick-borne encephalitis vaccinees aged 50-90 years. Vaccine. 2010 Apr 30;28(20):3511-5. doi: 10.1016/j.vaccine.2010.03.024. Epub 2010 Mar 21.

  PMID: 20332047 BACKGROUND

• Askling HH, Rombo L, van Vollenhoven R, Hallen I, Thorner A, Nordin M, Herzog C, Kantele A. Hepatitis A vaccine for immunosuppressed patients with rheumatoid arthritis: a prospective, open-label, multi-centre study. Travel Med Infect Dis. 2014 Mar-Apr;12(2):134-42. doi: 10.1016/j.tmaid.2014.01.005. Epub 2014 Jan 29.

  PMID: 24529746 BACKGROUND

• Wagner A, Garner-Spitzer E, Jasinska J, Kollaritsch H, Stiasny K, Kundi M, Wiedermann U. Age-related differences in humoral and cellular immune responses after primary immunisation: indications for stratified vaccination schedules. Sci Rep. 2018 Jun 29;8(1):9825. doi: 10.1038/s41598-018-28111-8.

  PMID: 29959387 BACKGROUND

• Hopf S, Garner-Spitzer E, Hofer M, Kundi M, Wiedermann U. Comparable immune responsiveness but increased reactogenicity after subcutaneous versus intramuscular administration of tick borne encephalitis (TBE) vaccine. Vaccine. 2016 Apr 12;34(17):2027-34. doi: 10.1016/j.vaccine.2015.12.057. Epub 2016 Jan 6.

  PMID: 26768126 BACKGROUND

• Garner-Spitzer E, Seidl-Friedrich C, Zwazl I, Hofer M, Kinaciyan T, Jarisch R, Stiasny K, Zlabinger GJ, Kundi M, Wiedermann U. Allergic patients with and without allergen-specific immunotherapy mount protective immune responses to tick-borne encephalitis vaccination in absence of enhanced side effects or propagation of their Th2 bias. Vaccine. 2018 May 11;36(20):2816-2824. doi: 10.1016/j.vaccine.2018.03.076. Epub 2018 Apr 16.

  PMID: 29673942 BACKGROUND

• Garner-Spitzer E, Wagner A, Paulke-Korinek M, Kollaritsch H, Heinz FX, Redlberger-Fritz M, Stiasny K, Fischer GF, Kundi M, Wiedermann U. Tick-borne encephalitis (TBE) and hepatitis B nonresponders feature different immunologic mechanisms in response to TBE and influenza vaccination with involvement of regulatory T and B cells and IL-10. J Immunol. 2013 Sep 1;191(5):2426-36. doi: 10.4049/jimmunol.1300293. Epub 2013 Jul 19.

  PMID: 23872054 BACKGROUND

• Svahn A, Linde A, Thorstensson R, Karlen K, Andersson L, Gaines H. Development and evaluation of a flow-cytometric assay of specific cell-mediated immune response in activated whole blood for the detection of cell-mediated immunity against varicella-zoster virus. J Immunol Methods. 2003 Jun 1;277(1-2):17-25. doi: 10.1016/s0022-1759(03)00111-x.

  PMID: 12799036 BACKGROUND

• Eliasson H, Olcen P, Sjostedt A, Jurstrand M, Back E, Andersson S. Kinetics of the immune response associated with tularemia: comparison of an enzyme-linked immunosorbent assay, a tube agglutination test, and a novel whole-blood lymphocyte stimulation test. Clin Vaccine Immunol. 2008 Aug;15(8):1238-43. doi: 10.1128/CVI.00434-07. Epub 2008 Jun 18.

  PMID: 18562568 BACKGROUND

MeSH Terms

Conditions

Encephalitis, Tick-Borne

Interventions

FSME-IMMUN vaccine

Condition Hierarchy (Ancestors)

Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Tick-Borne Diseases; Virus Diseases; RNA Virus Infections; Flavivirus Infections; Flaviviridae Infections; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases

Central Study Contacts

Anja Rosdahl

CONTACT

+46196021157; anja.rosdahl@regionorebrolan.se

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 21, 2020
• First Posted: October 5, 2020
• Study Start: January 1, 2024
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2025
• Last Updated: November 18, 2023

Record last verified: 2023-11

Locations

SE (1)