Abstract
Tick-borne encephalitis (TBE) is a disease that is found from western Europe across Asia and into Japan. In recent years the incidence rate has been increasing as has the endemic range of the virus. Tick-borne encephalitis is caused by three genetically distinct sutypes of viruses within a single TBE virus (TBEV) serocomplex. These three subtypes consist of Far-eastern subtype TBEV (TBEV-FE), Siberian subtype (TBEV-Sib) and European subtype (TBEV-Eu). Each of these subtypes cause clinically distinct diseases with varying degrees of severity. Development of the first vaccines for TBEV began in the late 1930s shortly after the first isolation of TBEV-FE in Russia. In the 1970s Austria began large scale vaccine production and a nationalized vaccine campaign that significantly reduced the incidence rate of TBE. Currently there are four licensed TBE vaccines, two in Europe and two in Russia. These vaccines are all quite similar formalin-inactivated virus vaccines but the each use a different virus strain for production. Published studies have shown that European vaccines are cross-protective in rodent studies and elicit cross-reactive neutralizing antibody responses in human vaccines. European vaccines have been licensed for a rapid vaccine schedule that could be used in response to a significant outbreak and reasonable neutralizing antibody titers can be achieved after a single dose although a second dose provides nearly complete and long-lasting protection. This review focuses on the current status of licensed TBE vaccines and provides a brief summary of technology currently being developed for new vaccines.
Highlights
The tick-borne encephalitis (TBE) serocomplex of flaviviruses (Family Flaviviridae, genus Flavivirus) includes a number of viruses that cause disease in humans
Omsk hemorrhagic fever virus (OHFV), Kyasanur Forest disease virus (KFDV) and ALKV are most frequently associated with hemorrhagic disease while Powassan virus (POWV) and TBE viruses (TBEV) infections can result in encephalitic disease
Disease seen following infection with KFDV and its subtypes generally consists of a hemorrhagic fever type of illness and may be associated with encephalitis whereas infection with OHFV is biphasic in about 50% of cases with limited neurologic manifestations [33]
Summary
The tick-borne encephalitis (TBE) serocomplex of flaviviruses (Family Flaviviridae, genus Flavivirus) includes a number of viruses that cause disease in humans. In 1957 a large outbreak of hemorrhagic disease in India was described in bonnet macaques and humans This disease was termed Kyasanur Forest disease (KFD), given its locale, and subsequent studies isolated the causative agent and characterized the virus as related to TBEV [30,31]. After isolation and characterization of LGTV, the Elantcev 15–20/3 strain of the virus was tested in human trials as a potential vaccine for prevention of more severe disease caused by the more virulent members of the TBE complex. Disease seen following infection with KFDV and its subtypes generally consists of a hemorrhagic fever type of illness and may be associated with encephalitis whereas infection with OHFV is biphasic in about 50% of cases with limited neurologic manifestations [33]. None of these novel vaccine strategies have reached clinical trials
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