A heterologous virus-vectored vaccine for prevention of Middle East respiratory syndrome induces long protective immune response against MERS-CoV

• Kovyrshina A.V.
• Dolzhikova I.V.
• Grousova D.M.
• Balyasin M.V.
• Botikov A.G.
• Panina L.V.
• Gordeychuk I.V.
• Gulyaev S.A.
• Zubkova O.V.
• Ozharovskaya T.A.
• Olga Popova
• Tukhvatulin A.I.
• Tokarskaya E.A.
• Simakova Ya.V.
• Esmagambetov I.B.
• Shcheblyakov D.V.
• Evgrafova I.M.
• Deryabin P.G.
• Borisevich S.V.
• Boris S. Naroditsky
• Denis Yu. Logunov
• Alexander L. Gintsburg

Abstract

Introduction. Middle East respiratory syndrome (MERS) is acute inflammatory disease of respiratory system with a high mortality, caused by coronavirus MERS-CoV. At present moment, we still lack specific therapeutic preparations and vaccines against MERS. Vaccine administration can help to limit the spread of the disease and lower the mortality. Duration of vaccine-induced immune response is one of the key characteristics of a vaccine, which is connected with duration of its protective effectiveness. Unfortunately, the data on duration of vaccine-induced immune response against MERS is scarce.

The aim of the study was to determine duration of humoral immune response in mice and primates and duration of protective immune response in mice after immunization with the heterologous virus-vectored vaccine against MERS (BVRS-GamVac-Combi), developed earlier by our research group.

Material and methods. To study duration of humoral immune response, we used mice of C57BL/6 strain and common marmosets. Animals were immunized with the vaccine BVRS-GamVac-Combi, based on recombinant adenoviral vectors rAd26 and rAd5. Antigen-specific-antibody titers were determined with ELISA, virus-neutralizing antibody titers were measured with virus neutralization assay using MERS-CoV (EMC/2012). To study duration of protective immune response, we used a model of lethal infection on transgenic mice, carrying human DPP4 gene of viral receptor.

Results. In present research, we showed that vaccination of animals with BVRS-GamVac-Combi induced robust humoral immune response, which persisted at least 18 months after immunization. In addition, our vaccine protected 100 % of animals from lethal infection for at least 7 months after immunization.

Conclusion. Strength of vaccine-induced immune response is generally connected with a protective effectiveness of a vaccine. One of the key problems of vaccine design is to find a way to provide as long and robust immune response as possible. Duration of vaccine-induced immune response is one of the key characteristics of a vaccine, which demands quality control during multiple steps of a vaccine development.

Keywords:vaccine; adenoviral vectors; Middle East respiratory syndrome (MERS); longevity of immune response

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