Single intranasal immunization with attenuated Wuhan-like SARS-CoV-2 provides highly effective cross-protection against Delta and Omicron variants of concern
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| 1. | Title | Title of document | Single intranasal immunization with attenuated Wuhan-like SARS-CoV-2 provides highly effective cross-protection against Delta and Omicron variants of concern |
| 2. | Creator | Author's name, affiliation, country | Evgeny B. Faizuloev; I.I. Mechnikov Research Institute of Vaccines and Sera; Russian Medical Academy of Continuous Professional Education; Россия |
| 2. | Creator | Author's name, affiliation, country | Anastasiia V. Gracheva; I.I. Mechnikov Research Institute of Vaccines and Sera; Россия |
| 2. | Creator | Author's name, affiliation, country | Ekaterina R. Korchevaya; I.I. Mechnikov Research Institute of Vaccines and Sera; Россия |
| 2. | Creator | Author's name, affiliation, country | Yulia I. Ammour; I.I. Mechnikov Research Institute of Vaccines and Sera; Россия |
| 2. | Creator | Author's name, affiliation, country | Daria I. Smirnova; I.I. Mechnikov Research Institute of Vaccines and Sera; Россия |
| 2. | Creator | Author's name, affiliation, country | Darya M. Khokhlova; I.I. Mechnikov Research Institute of Vaccines and Sera; Россия |
| 2. | Creator | Author's name, affiliation, country | Andrey O. Drokov; I.M. Sechenov First Moscow State Medical University (Sechenov University); Россия |
| 2. | Creator | Author's name, affiliation, country | Andrey A. Pankratov; P.A. Hertsen Moscow Oncology Research Institute; Россия |
| 2. | Creator | Author's name, affiliation, country | Galina V. Trunova; P.A. Hertsen Moscow Oncology Research Institute; Россия |
| 2. | Creator | Author's name, affiliation, country | Varvara A. Khokhlova; P.A. Hertsen Moscow Oncology Research Institute; Россия |
| 2. | Creator | Author's name, affiliation, country | Maria S. Vorontsova; P.A. Hertsen Moscow Oncology Research Institute; Россия |
| 2. | Creator | Author's name, affiliation, country | Irina A. Leneva; I.I. Mechnikov Research Institute of Vaccines and Sera; Россия |
| 2. | Creator | Author's name, affiliation, country | Oksana A. Svitich; I.I. Mechnikov Research Institute of Vaccines and Sera; I.M. Sechenov First Moscow State Medical University (Sechenov University); Россия |
| 2. | Creator | Author's name, affiliation, country | Vitaly V. Zverev; I.I. Mechnikov Research Institute of Vaccines and Sera; I.M. Sechenov First Moscow State Medical University (Sechenov University); Россия |
| 3. | Subject | Discipline(s) | |
| 3. | Subject | Keyword(s) | live attenuated COVID-19 vaccine; cold-adapted SARS-CoV-2; immunization efficacy; intranasal immunization; heterologous challenge; cross-protective immune response; golden Syrian hamsters |
| 4. | Description | Abstract | Introduction. Despite the end of the COVID-19 pandemic, the problem of vaccine prevention of this disease appears highly relevant. The emergence and widespread distribution of the Omicron SARS-CoV-2 variant of concern (VOC) and its sublineages has dramatically reduced the efficacy of vaccination. The possible approach to solving this problem is to develop a nasal live attenuated vaccine capable of activating humoral, mucosal, and cell-mediated immunity, providing a prolonged immune response and cross-protection against different VOCs. The aim of the study was to determine the immunization efficacy with attenuated cold-adapted Wuhan-like SARS-CoV-2 D-D2 strain against homologous and heterologous challenges. Materials and methods. The study was conducted on an animal model of coronavirus pneumonia in golden Syrian hamsters. The efficacy of immunization was assessed by comparing the dynamics of weight, viral load in organs and histopathological changes in the lungs in immunized and unimmunized animals. Results. Single intranasal immunization of golden Syrian hamsters with D-D2 strain showed its high immunogenicity: seroconversion was evident in all immunized animals. Wuhan-like D-D2 strain provides highly effective protection of hamsters against the development of productive infection and pneumonia when challenged both with ancestral virus and heterologous strains related to Delta (AY.122) and Omicron (sublineages BA.1.1 and BA.5.2) variants. Conclusion. SARS-CoV-2 attenuation is a promising strategy for the development of a highly effective nasal live COVID-19 vaccine. |
| 5. | Publisher | Organizing agency, location | Central Research Institute for Epidemiology |
| 6. | Contributor | Sponsor(s) |
The Russian Science Foundation (23-25-00146) Ministry of Education and Science of Russia |
| 7. | Date | (DD-MM-YYYY) | 13.03.2024 |
| 8. | Type | Status & genre | Peer-reviewed Article |
| 8. | Type | Type | Research Article |
| 9. | Format | File format | PDF (Rus), PDF (Eng), |
| 10. | Identifier | Uniform Resource Identifier | https://microbiol.crie.ru/jour/article/view/18552 |
| 10. | Identifier | Digital Object Identifier (DOI) | 10.36233/0372-9311-496 |
| 10. | Identifier | eLIBRARY Document Number (EDN) | zqbojh |
| 11. | Source | Title; vol., no. (year) | Journal of microbiology, epidemiology and immunobiology; Vol 101, No 1 (2024) |
| 12. | Language | English=en | en |
| 13. | Relation | Supp. Files |
Fig. 1. The design of the experiment for evaluating the immunization efficacy. (417KB) Fig. 2. Immunogenicity of the D-D2 strain in hamsters following single intranasal administration. Hamsters of G1–G4 groups were immunized with the D-D2 strain. a — titer of IgG antibody to SARS-CoV-2 proteins by ELISA; b — titers of neutralizing antibodies against different SARS-CoV-2 strains in the sera of all animals from groups G1–G4 (n = 24) — Dubrovka (Wuhan), Podolsk (Delta), Otradnoe (BA.1.1), and FEB2 (BA.5.2). The limit of detection was 20. ***p < 0.001. (317KB) Fig. 3. Weight change of immunized and unimmunized hamsters at days 1–4 post-challenge. (635KB) Fig. 4. Morphological changes of hamster lungs on day 4 post-challenge with different SARS-CoV-2 strains. Hematoxylin and eosin staining. The size of the scale bar is expressed in microns. (3MB) Fig. 5. Histopathology score for hamster lungs on day 4 post-challenge with different SARS-CoV-2 strains. *р < 0.05; **р < 0.01; ***р < 0.001. (210KB) Fig. 6. Virus titer in lungs, nasal passages, and brain of immunized and unimmunized hamsters. The limit of detection was 2.0 log10 TCID50/mL. (477KB) Fig. 7. Concentration of viral RNA in organs of immunized and unimmunized hamsters on 4 days post-challenge. a — lungs, nasal passages, blood, and brain; b — liver, heart, kidneys and spleen. The limit of detection was 3.0 log10 RNA copies/mL. *p < 0.05; **p < 0.01; ***p < 0.001. (826KB) |
| 14. | Coverage | Geo-spatial location, chronological period, research sample (gender, age, etc.) | |
| 15. | Rights | Copyright and permissions |
Copyright (c) 2024 Faizuloev E.B., Gracheva A.V., Korchevaya E.R., Ammour Y.I., Smirnova D.I., Khokhlova D.M., Drokov A.O., Pankratov A.A., Trunova G.V., Khokhlova V.A., Vorontsova M.S., Leneva I.A., Svitich O.A., Zverev V.V. This work is licensed under a Creative Commons Attribution 4.0 International License. |