Novel Universal Recombinant Rotavirus A Vaccine Candidate: Evaluation of Immunological Properties

新型通用重组轮状病毒A疫苗候选物:免疫学特性评估

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作者:Dmitriy L Granovskiy, Nelli S Khudainazarova, Ekaterina A Evtushenko, Ekaterina M Ryabchevskaya, Olga A Kondakova, Marina V Arkhipenko, Marina V Kovrizhko, Elena P Kolpakova, Tatyana I Tverdokhlebova, Nikolai A Nikitin, Olga V Karpova

Abstract

Rotavirus infection is a leading cause of severe dehydrating gastroenteritis in children under 5 years of age. Although rotavirus-associated mortality has decreased considerably because of the introduction of the worldwide rotavirus vaccination, the global burden of rotavirus-associated gastroenteritis remains high. Current vaccines have a number of disadvantages; therefore, there is a need for innovative approaches in rotavirus vaccine development. In the current study, a universal recombinant rotavirus antigen (URRA) for a novel recombinant vaccine candidate against rotavirus A was obtained and characterised. This antigen included sequences of the VP8* subunit of rotavirus spike protein VP4. For the URRA, for the first time, two approaches were implemented simultaneously-the application of a highly conserved neutralising epitope and the use of the consensus of the extended protein's fragment. The recognition of URRA by antisera to patient-derived field rotavirus isolates was proven. Plant virus-based spherical particles (SPs), a novel, effective and safe adjuvant, considerably enhanced the immunogenicity of the URRA in a mouse model. Given these facts, a URRA + SPs vaccine candidate is regarded as a prospective basis for a universal vaccine against rotavirus.

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