Recombinant domains III of Tick-Borne Encephalitis Virus envelope protein in combination with dextran and CpGs induce immune response and partial protectiveness against TBE virus infection in mice

蜱传脑炎病毒包膜蛋白的重组结构域 III 与葡聚糖和 CpG 结合可在小鼠中诱导免疫反应并产生针对 TBE 病毒感染的部分保护作用

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作者:Anna S Ershova, Olga A Gra, Alexander M Lyaschuk, Tatyana M Grunina, Artem P Tkachuk, Mikhail S Bartov, Darya M Savina, Olga V Sergienko, Zoya M Galushkina, Vladimir P Gudov, Liubov I Kozlovskaya, Ivan S Kholodilov, Larissa V Gmyl, Galina G Karganova, Vladimir G Lunin, Anna S Karyagina, Alexander L

Background

E protein of tick-borne encephalitis virus (TBEV) and other flaviviruses is located on the surface of the viral particle. Domain III of this protein seems to be a promising component of subunit vaccines for prophylaxis of TBE and kits for diagnostics of TBEV.

Conclusions

Studied proteins interact with the sera of TBE patients, and, in combination with dextran and CPGs, demonstrate immunogenicity and limited protectivity on mice compared with reference "Tick-E-Vac" vaccine.

Methods

Three variants of recombinant TBEV E protein domain III of European, Siberian and Far Eastern subtypes fused with dextran-binding domain of Leuconostoc citreum KM20 were expressed in E. coli and purified. The native structure of domain III was confirmed by ELISA antibody kit and sera of patients with tick-borne encephalitis. Immunogenic and protective properties of the preparation comprising these recombinant proteins immobilized on a dextran carrier with CpG oligonucleotides as an adjuvant were investigated on the mice model.

Results

All 3 variants of recombinant proteins immobilized on dextran demonstrate specific interaction with antibodies from the sera of TBE patients. Thus, constructed recombinant proteins seem to be promising for TBE diagnostics. The formulation comprising the 3 variants of recombinant antigens immobilized on dextran and CpG oligonucleotides, induces the production of neutralizing antibodies against TBEV of different subtypes and demonstrates partial protectivity against TBEV infection. Conclusions: Studied proteins interact with the sera of TBE patients, and, in combination with dextran and CPGs, demonstrate immunogenicity and limited protectivity on mice compared with reference "Tick-E-Vac" vaccine.

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