Tick-borne Encephalitis Vaccine

Tick-borne encephalitis (TBE) is an acute viral illness caused by two closely related viruses of the family Flaviviridae: the central European encephalitis (CEE) virus, found in many European countries, and the Russian spring-summer encephalitis (RSSE) virus, found predominantly in the Asian parts of the former Soviet Union. These viruses, which are endemic to forested areas, are transmitted by ticks. In addition to humans, they infect small mammals and, to a lesser extent, birds. In Asia, the disease is characterized by abrupt onset of fever, severe headache, nausea and vomiting and severe back pain often associated with focal epilepsy and flaccid paralysis, especially of the shoulder girdle. Such paralysis may be permanent. The central European form of the disease has a longer course, often with biphasic fever, but severe sequelae are less frequent. The initial febrile stage is normally not associated with disease of the central nervous system, but the second phase, following approximaely 4-10 days after apparent recovery, is characterized by fever and meningoencephalitis. The case-fatality rate is approximately 20% for the Asian form of the disease and 1-5% for the European form.

TBE is endemic to most European countries, the Russian Federation and possibly China. It is the most important arthropod-transmitted viral disease in Europe, and in some countries it represents a major public-health problem. The disease has been known by several names, including RSSE, Far Eastern encephalitis and CEE.

CEE virus is found is every European country, with the exception of Belgium, Luxembourg, the Netherlands, Portugal, Spain and the United Kingdom, and is transmitted primarily by the tick Ixodes ricinus. RSSE virus is most prevalent in the eastern part of the former Soviet Union and is transmitted by the tick Ixodes persulcatus.

Flaviviruses are a large group of small, enveloped viruses responsible for a number of severe human diseases, including yellow fever, Japanese encephalitis, dengue haemorrhagic fever and TBE. TBE virus particles are roughly spherical in shape, 40-50nm in diameter, and contain a core, 20-30nm in diameter. The genome consists of single-stranded positive-sense RNA with a relative molecular mass of about 4x10(6). Three structural proteins and the capsid, membrane and envelope proteins are all encoded by the viral genome. The envelope glycoprotein induces neutralizing and haemagglutination-inhibition antibodies and is the most important antigen for providing protection from disease.

The first vaccine against TBE was prepared in 1941 in the brains of mice. Some 20 years later TBE vaccines derived from cell cultures (chicken embryo fibroblast cells) were developed and used for active immunization in humans in the former Soviet Union. Later, a purified, inactivated virus vaccine was developed which proved to be more immunogenic than previous TBE vaccines.

The efficacy of these vaccines has been well documented. They have also been shown to protect mice from a lethal challenge with several TBE-virus isolates obtained over a period of more than 30 years from all over Europe and the Asian part of the former Soviet Union. In addition, it has been demonstrated that antibodies induced by vaccination of human volunteers neutralized all tested isolates.

Large outbreaks of TBE, sometimes involving thousands of cases, continue to occur in endemic areas. In addition, certain special groups, such as forest workers, geologists, travellers to endemic areas and laboratory workers, are also at risk. In view of the need to immunize large numbers of people, requirements for inactivated TBE vaccine have been formulated. In drafting these requirements, account has been taken of the regulations and requirements for the manufacture and control of TBE vaccines that have already been established in several countries.



TRS 1004 - WHO Expert Committee on Biological Standardization, Sixty-seventh report


  • WHO Working Group meeting on Respiratory Syncytial Virus (RSV) Vaccine Standardization, WHO headquarters, Geneva, Switzerland, 13-15 September 2017
  • WHO Second Working Group Meeting on Developing WHO Guidelines on safe production of polio vaccines, WHO HQ Salle D, 19-20 September 2017
  • WHO Workshop on Implementation of Good Manufacturing Practices for Biological Products, Bangkok, Thailand 15-17 November 2017
  • WHO Implementation Workshop on the Quality, Safety and Efficacy of Typhoid Conjugate Vaccines, Osong, Chungju-si, The Republic of Korea, 21-13 November 2017


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