Can the booster interval for the tick-borne encephalitis (TBE) vaccine ‘FSME-IMMUN’ be prolonged? — A systematic review

Tick-borne encephalitis (TBE) vaccines are effective and well tolerated. However, their acceptance and use by the public in endemic areas are suboptimal. To some extent this is due to the complicated dosing schedule requiring frequent boosters at variable intervals that even change with age. Simplification of the dosing schedule has failed so far as it is debated if the persistence of TBE virus (TBEV) antibodies is the only relevant factor for protection or if immune memory plays a decisive role as well. The objective here is to present the available evidence to determine the need for boosters and their interval after a primary series of three doses of FSME-IMMUN. A systematic literature review was conducted with a focus on serology, particularly seropersistence, immune memory, effectiveness, and vaccine breakthroughs (VB) of FSME-IMMUN. While after a 3-dose primary series seropositivity persisted for more than 10 years in >90% of younger subjects, it dropped to 37.5% in those 60 years or older. In contrast, field effectiveness of FSME-IMMUN remains high in irregularly vaccinated subjects and thus does not correlate well with the percentage of subjects achieving an arbitrarily defined threshold of persisting antibodies. FSME-IMMUN booster doses led to increases in antibody responses within 7 days. VB are rare and remain poorly understood. VB did not increase, and vaccine effectiveness did not significantly decrease with time since completion of the primary vaccination series or with the time since administration of the last vaccine dose. For all these reasons, data identified from this systematic review suggest that seropersistence alone does not explain the high effectiveness of FSME-IMMUN irrespective of the time since the last vaccine dose was administered. Induction of immunological memory characterized by a rapid and sustained secondary immune response is proving to be an alternative mechanism of action for protection against TBE. In this context Switzerland and Finland have adopted a longer booster interval (i.e., 10 years) following the three-dose primary immunization schedule without any evidence of harm at a population level. Longer booster intervals will likely drive up vaccine uptake. There is a lack of data to base an interval recommendation beyond 10 years