A Tick-borne Encephalitis Virus Vaccine Based on the European Prototype Strain Induces Broadly Reactive Cross-neutralizing Antibodies in Humans

Abstract

After vaccination of humans with tick-borne encephalitis virus (TBEV) vaccine, the extent of cross-neutralization between viruses of the European, Far Eastern, and Siberian subtypes of TBEV and Omsk hemorrhagic fever virus (OHFV) was analyzed. Hybrid viruses that encode the TBEV surface proteins for representative viruses within all subtypes, and OHFV, were constructed using the West Nile virus (WNV) backbone as vector. These viruses allow for unbiased head-to-head comparison in neutralization assays because they exhibit the antigenic characteristics of the TBEV strains from which the surface proteins were derived and showed equivalent biologic properties in cell culture. Human serum samples derived from a TBEV vaccine trial were analyzed and revealed comparable neutralizing antibody titers against European, Far Eastern, and Siberian subtype viruses, indicating equally potent cross-protection against these TBEV strains and a somewhat reduced but still protective neutralization capacity against more distantly related viruses, such as OHFV.

Single-dose vaccine against tick-borne encephalitis

“…Because of a high degree of homology in the E protein (∼95%), they comprise a single serotype, and a vaccine based on a TBE strain from one subtype is effective against all virus subtypes as evidenced by numerous previous studies using INVs (33)(34)(35). The fact that RepliVax-TBE protected monkeys from a surrogate challenge with a genetically distant LGT virus indicates that this vaccine will be broadly protective.…”

Persistence of antibodies six years after booster vaccination with inactivated vaccine against Japanese encephalitis

“…Belonging to the same family of viruses, it has been discussed whether there may be any interference or cross-reactivity of antibodies against JE with those from other flaviviruses as these viruses have highly conserved envelope protein amino acid sequences [19][20][21][22]. This was addressed in an investigation also using the SA 14 -14-2 vaccine in 420 subjects where JE antibody titers were significantly higher during basic immunization course after the first JE vaccination but not after the second in persons with anti-TBE antibodies compared to subjects without TBE vaccination [23].…”

Analysis of Efficacy and Safety of Tick-Borne Encephalitis Vaccines

“…Среднегеометрический титр антител, определяемых в реакции ИФА и РТГА, был выше у мышей, иммунизированных вакциной ЭнцеВир ® , чем при иммунизации другими вакцинами КЭ [36]. Установлена способность вакцины ФСМЕ-Иммун ® ин-дуцировать перекрестную вируснейтрализующую активность антител у здоровых доноров к штаммам-гибридам европейско-го подтипа -Neudoerfl и К-23, дальневосточного подтипа -Sofjin-HO и Oshhima, сибирского подтипа -Vasilchenko [37]. Результаты сравнительного изучения иммуногенности вакцин против КЭ показали высокую иммунологическую активность всех вакцин.…”