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Vol 54(2020) N 6 p. 812-826; DOI 10.1134/S0026893320060151 T.A. Zaichuk1, Y.D. Nechipurenko2*, A.A. Adzhubey2,3, S.B. Onikienko4, V.A. Chereshnev5, S.S. Zainutdinov6, G.V. Kochneva6, S.V. Netesov7, O.V. Matveeva1,8** The Challenges of Vaccine Development Against Betacoronaviruses: Antibody Dependent Enhancement and Sendai Virus as a Possible Vaccine Vector 1Sendai Viralytics, Acton, MA, 117261 USA2Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia 3George Washington University, Washington, DC, 20052 USA 4Department of Military Field Therapy, Kirov Military Medical Academy, St. Petersburg, 194044 Russia 5Institute of Immunology and Physiology, Yekaterinburg, 620049 Russia 6State Research Center of Virology and Biotechnology "Vector", Koltsovo, 630559 Russia 7Department of Natural Sciences, Novosibirsk State University, Novosibirsk, 630090 Russia 8Biopolymer Design, Acton, MA, 117281 USA *Nech99@mail.ru **Olga.Matveeva@gmail.com Received - 2020-04-30; Revised - 2020-06-04; Accepted - 2020-06-05 To design an effective and safe vaccine against betacoronaviruses, it is necessary to elicit a combination of strong humoral and cell-mediated immune responses as well as to minimize the risk of antibody-dependent enhancement of viral infection. This phenomenon was observed in animal trials of experimental vaccines against SARS-CoV-1 and MERS-CoV that were developed based on inactivated coronavirus or vector constructs expressing the spike protein (S) of the virion. The substitution and glycosylation of certain amino acids in the antigenic determinants of the S-protein, as well as its conformational changes, can lead to the same effect in a new experimental vaccine against SARS-CoV-2. This review outlines approaches for developing vaccines against the new SARS-CoV-2 coronavirus that are based on non-pathogenic viral vectors. For efficient prevention of infections caused by respiratory pathogens the ability of the vaccine to stimulate mucosal immunity in the respiratory tract is important. Such a vaccine can be developed using non-pathogenic Sendai virus vector, since it can be administered intranasally and induce a mucosal immune response that strengthens the antiviral barrier in the respiratory tract and provides reliable protection against infection. The mucosal immunity and the production of IgA antibodies accompanying its development reduces the likelihood of developing an antibody-dependent infection enhancement, which is usually associated only with immunopathological IgG antibodies. SARS-CoV-2, SARS-CoV-1, COVID-19, antibody-dependent enhancement, ADE, vaccine vector, Sendai virus, murine respirovirus, conservative antigenic determinants |