Primary TBE Vaccination for the Elderly

Vaccine Clinical Trial

Official title:

Primary TBE Vaccination for the Elderly

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04573205
• Other study ID #: O2019-1
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: January 2024
• Est. completion date: January 2025

Study information

• Verified date: November 2023
• Source: Region Örebro County
• Contact: Anja Rosdahl
• Phone: +46196021157
• Email: anja.rosdahl[@]regionorebrolan.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 90
• Est. completion date: January 2025
• Est. primary completion date: January 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults = 50 years or between 18-40 years

• Man or woman

• God health

• Written informed consent

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Encephalitis
• Encephalitis, Tick-Borne
• Tick-borne Encephalitis
• Vaccine

Intervention

Drug:
• FSME-IMMUN Vaccine
0.5 ml intramuscular injection scheduled in the two different arms

Locations

Country	Name	City	State
Sweden	Region Örebro Län	Örebro

Sponsors (1)

Lead Sponsor	Collaborator
Region Örebro County

Country where clinical trial is conducted

Sweden, 

References & Publications (15)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Cellular immunity in young and elderly ( immune cell expression)	T and B cell populations (flow cytometry) 7 days after TBE vaccination	Measured 7 days after vaccination
Secondary	Cellular immunity in young and elderly ( cytokine production)	Cytokine production ( Luminex) 7 days after TBE vaccination	Measured 7 days after vaccination