Elsevier

Vaccine

Volume 27, Issue 10, 4 March 2009, Pages 1661-1666
Vaccine

Antibody response following administration of two paediatric tick-borne encephalitis vaccines using two different vaccination schedules

https://doi.org/10.1016/j.vaccine.2008.10.003Get rights and content

Abstract

Two paediatric tick-borne encephalitis vaccines, Encepur® Children and FSME-IMMUN® Junior, are used widely in Europe. This study compared the immunogenicity and safety of both vaccines, administered using the conventional (Days 0, 28, and 300) or accelerated (Days 0, 14, and 300) schedule and evaluated whether a third dose of Encepur® Children can complete a primary vaccination course initiated with FSME-IMMUN® Junior. A total of 334 children 1 to <11 years of age were enrolled in this Phase IV randomized, controlled, single-blind, multi-centre trial. All subjects, irrespective of study arm, received Encepur® Children as the third dose on Day 300. The percentage of subjects with antibody titres ≥10, as determined by neutralization test (NT), was assessed and local and systemic reactions were monitored and solicited. Within both the conventional and accelerated schedules, the proportion of subjects achieving an NT  10 was higher in the group that received Encepur® Children, compared with the group that received FSME-IMMUN® Junior, at Days 42 and 300 (conventional schedule Day 300, P < 0.001 Encepur® Children versus FSME-IMMUN® Junior; accelerated schedule Days 42 and 300, P < 0.001 Encepur® Children versus FSME-IMMUN® Junior). The third dose of Encepur® Children led to a substantial increase in the proportion of subjects in the FSME-IMMUN® Junior groups achieving NT  10. Overall, >95% of all children achieved NT  10, on completion of the primary vaccination course. Encepur® Children provides an immune response, measured by neutralizing TBE antibodies, that is superior to FSME-IMMUN® Junior and can successfully be used to complete a primary vaccination course initiated with FSME-IMMUN® Junior. Both vaccines were well tolerated, with comparable safety profiles; no vaccine-related serious adverse events were reported.

Introduction

Tick-borne encephalitis (TBE) is a viral infection that affects the central nervous system (CNS). The course of the disease is typically biphasic, with the first stage characterized by influenza-like symptoms. Approximately one-third of patients who develop the first stage of TBE will progress to the second stage of the disease, which is characterized by acute CNS infection following a period of afebrile remission [1]. Infections may result in long-term neurological sequelae or can be fatal [2].

Tick-borne encephalitis is endemic in many areas of Western Europe and certain areas of Scandinavia, and extends eastwards through Russia to Japan [2]. Over the last 30 years, the incidence of TBE has increased in nearly all European countries (except Austria) [3]; in Lithuania, where vaccination coverage rates are very low, TBE incidence increased 10-fold [4], [5]. In the Czech Republic, the increase in the incidence of TBE (2005–2006) was particularly pronounced in children 6–9 and 15–19 years of age (4.9- and 2.5-fold increases, respectively) [4], [6], suggesting insufficient vaccination coverage in these age groups.

On average, 11–20% of TBE cases occur in children [7], [8], [9], and these may lead to permanent neurological disabilities, underlining the need for disease prevention in this age group [10], [11]. As there is no curative treatment for TBE, prevention by active vaccination is considered the most effective strategy. The TBE vaccination campaign in Austria has significantly reduced the incidence of the disease, with approximately 50–60 cases recorded annually, compared with 600 cases per year reported before initiation of the vaccination campaign [12].

Two paediatric TBE vaccines are widely used in Europe: Encepur® Children (Novartis Vaccines and Diagnostics GmbH & Co., Marburg, Germany) and FSME-IMMUN® Junior (Baxter AG, Vienna, Austria). Both vaccines can be administered using a conventional vaccination schedule, which comprises three doses to complete the primary vaccination course (Encepur® Children, Day 0, Months 1–3 and Months 9–12; FSME-IMMUN® Junior Day 0, Months 1–3 and Months 5–12). When faster protection against TBE is required, primary vaccination can be administered with Encepur® Children using the rapid schedule (Days 0, 7, and 21) or with FSME-IMMUN® Junior using the accelerated schedule (Days 0 and 14, and Months 5–12).

Although TBE vaccination strategies have been in place in several European countries for a number of years, there have been no studies published to date that directly compare the immunogenicity and safety profiles of the two currently licensed TBE vaccines in the paediatric population. In addition, no publications have described in detail antibody persistence between Doses 2 and 3 when using the accelerated schedule.

The aims of the current study were to evaluate and compare the immunogenicity and safety of Encepur® Children and FSME-IMMUN® Junior when administered using either the conventional or accelerated schedule, focusing on antibody persistence between Doses 2 and 3 of the primary vaccination course. Furthermore, to assess vaccine interchangeability during the primary vaccination course, Encepur® Children was administered to all children as the third dose. Here, immunogenicity, defined as the proportion of children responding to vaccination, has been reported; the kinetic response to vaccination has been reported elsewhere [13].

Section snippets

Materials and methods

This study was a randomized, controlled, single-blind trial, performed in 11 centres across Germany between March 2005 and July 2006. Children 1 to <11 years of age were eligible for inclusion; those with prior TBE disease or TBE vaccination, known hypersensitivity to any component of the vaccines, or concurrent major illness, were excluded. At study entry, eligible children were stratified by age (1–2, 3–5 and 6–10 years of age) and study centre, and then randomized by age stratum to 1 of 4

Results

A total of 334 children 1 to <11 years of age were enrolled in the study. The demographic characteristics of both of the randomized groups were well matched, with more male subjects enrolled in each group compared with female subjects (Table 1).

Discussion

This study evaluated and compared the immune response to the two paediatric TBE vaccines Encepur® Children and FSME-IMMUN® Junior, which are widely used in Europe, administered using two different vaccination schedules. The results indicate that a higher proportion of children achieved an NT  10 following two doses of Encepur® Children compared with FSME-IMMUN® Junior, using either vaccination schedule. Furthermore, the data show that the proportion of children achieving an NT  10 was higher when

Conclusion

This study is the first head-to-head comparison of Encepur® Children and FSME-IMMUN® Junior, using two different immunization schedules. It is also the first comprehensive clinical study to consider the interchangeability of vaccines within the primary vaccination course, using Encepur® Children as the third dose. The results clearly demonstrate that: (1) using either schedule, significantly (P  0.001) more children had an immune response (NT  10) at Day 300 when vaccinated with Encepur®

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