rAAV expressing recombinant antibody for emergency prevention and long-term prophylaxis of COVID-19

Frontiers in Immunology

Immunology

Dmitry V. Shcheblyakov¹  Ilias B. Esmagambetov¹  Daria V. Byrikhina¹  Artem A. Derkaev¹  Artem Y. Shelkov¹  Daria M. Grousova¹  Andrey I. Gosudarev¹  Ekaterina I. Ryabova¹  Irina A. Favorskaya¹  Vladimir V. Prokofiev¹  Boris S. Naroditsky¹  Mikhail A. Dovgiy¹  Anna A. Iliukhina¹  Anna V. Kovyrshina¹  Denis Y. Logunov¹  Alexander L. Gintsburg¹  Inna V. Dolzhikova¹  Ilia D. Zorkov¹ 

[1] Federal State Budget Institution, National Research Center for Epidemiology and Microbiology Named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation, Moscow, Russia;

关键词: recombinant adeno-associated viral vector (rAAV);    single-domain antibodies;    VHH;    COVID-19;    SARS-CoV-2;    passive immunization;    prophylaxis;   

DOI  :  10.3389/fimmu.2023.1129245

 received in 2022-12-21, accepted in 2023-03-15,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionNumerous agents for prophylaxis of SARS-CoV-2-induced diseases are currently registered for the clinical use. Formation of the immunity happens within several weeks following vaccine administration which is their key disadvantage. In contrast, drugs based on monoclonal antibodies, enable rapid passive immunization and therefore can be used for emergency pre- and post-exposure prophylaxis of COVID-19. However rapid elimination of antibody-based drugs from the circulation limits their usage for prolonged pre-exposure prophylaxis.MethodsIn current work we developed a recombinant adeno-associated viral vector (rAAV), expressing a SARS-CoV-2 spike receptor-binding domain (RBD)-specific antibody P2C5 fused with a human IgG1 Fc fragment (P2C5-Fc) using methods of molecular biotechnology and bioprocessing.Results and discussionsA P2C5-Fc antibody expressed by a proposed rAAV (rAAV-P2C5-Fc) was shown to circulate within more than 300 days in blood of transduced mice and protect animals from lethal SARS-CoV-2 virus (B.1.1.1 and Omicron BA.5 variants) lethal dose of 105 TCID50. In addition, rAAV-P2C5-Fc demonstrated 100% protective activity as emergency prevention and long-term prophylaxis, respectively. It was also demonstrated that high titers of neutralizing antibodies to the SARS-CoV-2 virus were detected in the blood serum of animals that received rAAV-P2C5-Fc for more than 10 months from the moment of administration.Our data therefore indicate applicability of an rAAV for passive immunization and induction of a rapid long-term protection against various SARS-CoV-2 variants.

【 授权许可】

Unknown   
Copyright © 2023 Esmagambetov, Ryabova, Derkaev, Shcheblyakov, Dolzhikova, Favorskaya, Grousova, Dovgiy, Prokofiev, Gosudarev, Byrikhina, Zorkov, Iliukhina, Kovyrshina, Shelkov, Naroditsky, Logunov and Gintsburg