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Development of a Platform for Producing Recombinant Protein Components of Epitope Vaccines for the Prevention of COVID-19.
Karyagina, Anna S; Gromov, Alexander V; Grunina, Tatyana M; Lyaschuk, Alexander M; Grishin, Alexander V; Strukova, Natalia V; Generalova, Maria S; Galushkina, Zoya M; Soboleva, Lyubov' A; Dobrinina, Olga Yu; Bolshakova, Tatyana N; Subbotina, Marina E; Romanovskaya-Romanko, Ekaterina A; Krasilnikov, Igor V; Polyakov, Nikita B; Solovyev, Andrey I; Grumov, Daniil A; Zhukhovitsky, Vladimir G; Ryabova, Ekaterina I; Prokofiev, Vladimir V; Lunin, Vladimir G.
  • Karyagina AS; Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, 123098, Russia. akaryagina@gmail.com.
  • Gromov AV; All-Russia Research Institute of Agricultural Biotechnology, Moscow, 127550, Russia.
  • Grunina TM; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, 119992, Russia.
  • Lyaschuk AM; Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, 123098, Russia.
  • Grishin AV; Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, 123098, Russia.
  • Strukova NV; All-Russia Research Institute of Agricultural Biotechnology, Moscow, 127550, Russia.
  • Generalova MS; Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, 123098, Russia.
  • Galushkina ZM; Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, 123098, Russia.
  • Soboleva LA; Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, 123098, Russia.
  • Dobrinina OY; Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, 123098, Russia.
  • Bolshakova TN; Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, 123098, Russia.
  • Subbotina ME; Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, 123098, Russia.
  • Romanovskaya-Romanko EA; Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, 123098, Russia.
  • Krasilnikov IV; Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, 123098, Russia.
  • Polyakov NB; Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, 123098, Russia. subbotinam@gmail.com.
  • Solovyev AI; All-Russia Research Institute of Agricultural Biotechnology, Moscow, 127550, Russia.
  • Grumov DA; Institute of Influenza, Ministry of Health of the Russian Federation, St. Petersburg, 197376, Russia.
  • Zhukhovitsky VG; Saint Petersburg Institute of Vaccines and Sera, FMBA, St. Petersburg, 198320, Russia.
  • Ryabova EI; Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, 123098, Russia.
  • Prokofiev VV; Vernadsky Institute of Geochemistry and Analytical Chemistry, Russian Academy of Sciences, Moscow, 119991, Russia.
  • Lunin VG; Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow, 123098, Russia.
Biochemistry (Mosc) ; 86(10): 1275-1287, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1476404
ABSTRACT
A new platform for creating anti-coronavirus epitope vaccines has been developed. Two loop-like epitopes with lengths of 22 and 42 amino acid residues were selected from the receptor-binding motif of the Spike protein from the SARS-CoV-2 virus that participate in a large number of protein-protein interactions in the complexes with ACE2 and neutralizing antibodies. Two types of hybrid proteins, including one of the two selected epitopes, were constructed. To fix conformation of the selected epitopes, an approach using protein scaffolds was used. The homologue of Rop protein from the Escherichia coli ColE1 plasmid containing helix-turn-helix motif was used as an epitope scaffold for the convergence of C- and N-termini of the loop-like epitopes. Loop epitopes were inserted into the turn region. The conformation was additionally fixed by a disulfide bond formed between the cysteine residues present within the epitopes. For the purpose of multimerization, either aldolase from Thermotoga maritima, which forms a trimer in solution, or alpha-helical trimerizer of the Spike protein from SARS-CoV-2, was attached to the epitopes incorporated into the Rop-like protein. To enable purification on the heparin-containing sorbents, a short fragment from the heparin-binding hemagglutinin of Mycobacterium tuberculosis was inserted at the C-terminus of the hybrid proteins. All the obtained proteins demonstrated high level of immunogenicity after triplicate parenteral administration to mice. Sera from the mice immunized with both aldolase-based hybrid proteins and the Spike protein SARS-CoV-2 trimerizer-based protein with a longer epitope interacted with both the inactivated SARS-CoV-2 virus and the Spike protein receptor-binding domain at high titers.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 / Epitopes Topics: Vaccines Limits: Animals / Female / Humans Language: English Journal: Biochemistry (Mosc) Year: 2021 Document Type: Article Affiliation country: S0006297921100096

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 / Epitopes Topics: Vaccines Limits: Animals / Female / Humans Language: English Journal: Biochemistry (Mosc) Year: 2021 Document Type: Article Affiliation country: S0006297921100096