Abstract
The tick-borne encephalitis complex contains a number of flaviviruses that share close genetic homology, and are responsible for significant human morbidity and mortality with widespread geographical range. Although many members of this complex have been recognised for decades, licenced human vaccines with broad availability are only available for tick-borne encephalitis virus. While tick-borne encephalitis virus vaccines have been demonstrated to induce significant protective immunity, as determined by virus-neutralisation titres, vaccine breakthrough (clinical infection following complete vaccination), has been described. The aim of this study was to confirm the cross-neutralisation of tick-borne flaviviruses using mouse immune ascitic fluids, and to determine the magnitude of cross-neutralising antibody titres in sera from donors following tick-borne encephalitis vaccination, infection, and vaccine breakthrough. The results demonstrate that there is significant cross-neutralisation of representative members of the tick-borne encephalitis complex following vaccination and/or infection, and that the magnitude of immune responses varies based upon the exposure type. Donor sera successfully neutralised most of the viruses tested, with 85% of vaccinees neutralising Kyasanur forest disease virus and 73% of vaccinees neutralising Alkhumra virus. By contrast, only 63% of vaccinees neutralised Powassan virus, with none of these neutralisation titres exceeding 1:60. Taken together, the data suggest that tick-borne encephalitis virus vaccination may protect against most of the members of the tick-borne encephalitis complex including Kyasanur forest disease virus and Alkhumra virus, but that the neutralisation of Powassan virus following tick-borne encephalitis vaccination is minimal.
Highlights
The tick-borne encephalitis (TBE) complex is a group of enveloped, non-segmented, positive-sensed single-stranded RNA viruses within the genus Flavivirus.[1]
The high mortality associated with a number of the members of the TBE complex has led to their classification as risk-group four pathogens in non-endemic countries, requiring work with these viruses to be restricted to Biosafety Level 4 (BSL-4) facilities.[7]
The TBE complex is a group of significant human pathogens that share a relatively high degree of genetic similarity
Summary
The tick-borne encephalitis (TBE) complex is a group of enveloped, non-segmented, positive-sensed single-stranded RNA viruses within the genus Flavivirus (family Flaviviridae).[1] Many of the viruses of the TBE complex are significant human pathogens, such as tick-borne encephalitis virus (TBEV), Omsk haemorrhagic fever virus (OHFV), Kyasanur forest disease virus (KFDV), and Powassan virus (POWV), and have a wide global distribution spanning North America, Europe, the Middle East, and Asia.[2] The viruses display substantial sequence similarity at both the nucleotide and aminoacid level, with the two most genetically distant members of the complex (POWV and Alkhumra haemorrhagic fever virus [AHFV]). 2,600 cases annually in Europe, KFDV causing an average of 400–500 cases per year in India, and AHFV causing approximately 20 cases a year in the Middle East.[4,5,6] The high mortality associated with a number of the members of the TBE complex has led to their classification as risk-group four pathogens in non-endemic countries, requiring work with these viruses to be restricted to Biosafety Level 4 (BSL-4) facilities.[7]
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