Shchelkunov S N, Yakubitskiy S N, Bauer T V, Sergeev A A, Kabanov A S, Bulichev L E, Yurganova I A, Odnoshevskiy D A, Kolosova I V, Pyankov S A, Taranov O S
State Research Center of Virology and Biotechnology VECTOR, Rospoterbnadzor, Novosibirsk region, Koltsovo, 630559 Russia.
Acta Naturae. 2020 Oct-Dec;12(4):120-132. doi: 10.32607/actanaturae.10972.
The modern approach to developing attenuated smallpox vaccines usually consists in targeted inactivation of vaccinia virus (VACV) virulence genes. In this work, we studied how an elevated production of extracellular enveloped virions (EEVs) and the route of mouse infection can influence the virulence and immunogenicity of VACV. The research subject was the LIVP strain, which is used in Russia for smallpox vaccination. Two point mutations causing an elevated production of EEVs compared with the parental LIVP strain were inserted into the sequence of the VACV gene. The created mutant LIVP-A34R strain showed lower neurovirulence in an intracerebral injection test and elevated antibody production in the intradermal injection method. This VACV variant can be a promising platform for developing an attenuated, highly immunogenic vaccine against smallpox and other orthopoxvirus infections. It can also be used as a vector for designing live-attenuated recombinant polyvalent vaccines against various infectious diseases.
现代开发减毒天花疫苗的方法通常包括对痘苗病毒(VACV)毒力基因进行靶向灭活。在这项工作中,我们研究了细胞外包膜病毒粒子(EEV)产量的提高以及小鼠感染途径如何影响VACV的毒力和免疫原性。研究对象是俄罗斯用于天花疫苗接种的LIVP株。与亲本LIVP株相比,导致EEV产量提高的两个点突变被插入到VACV基因序列中。所构建的突变体LIVP-A34R株在脑内注射试验中显示出较低的神经毒力,在皮内注射法中抗体产量有所提高。这种VACV变体可能是开发一种针对天花和其他正痘病毒感染的减毒、高免疫原性疫苗的有前途的平台。它还可以用作载体来设计针对各种传染病的减毒活重组多价疫苗。