Immunogenicity and efficacy of SOBERANA® 02 against SARS-CoV-2, in the Syrian golden hamster animal model
Keywords:
animal models, COVID-19 vaccine, SARS-CoV-2, vaccine efficacyAbstract
Introduction: In preclinical studies of the vaccine SOBERANA®02, it was essential to verify the efficacy of the immune response against SARS-CoV-2 in animal models. In a challenge assay, animals immunized with the vaccine antigen are exposed to the virus in a controlled manner.
Objectives: To evaluate the immunogenicity and protection of FR02 antigen against SARS-CoV-2 in the Syrian golden hamster model.
Methods: Immunized hamsters were challenged with the viral variant D614G. Body weight, respiratory signs, presence of viral RNA in nasopharynx and lung tissue were monitored. Cultures were performed on Vero E6 cells and histopathological analysis of the lungs. Unvaccinated infected animals and unvaccinated and uninfected animals were used as controls.
Results: Immunized hamsters showed no signs of disease; viral RNA concentrations in nasopharynx and lungs were lower than unvaccinated infected hamsters, with reduced viral load (6 logarithms) in the lungs on the day of peak viral replication, and undetectable in 27.7%. A cytopathic effect was observed in 5.8% of viral cultures in the lungs of immunized vs. non-immunized infected animals, in which it occurred in 100%. Immunized hamsters had lower rates of acute lung damage and overall histological damage.
Conclusions: The immune response generated in immunized animals conferred protection against infection, severe lung damage and the development of symptomatic disease in hamsters.
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References
1. Organización Mundial de la Salud. Declaración sobre la segunda reunión del Comité de emergencias del reglamento Sanitario Internacional acerca del brote del nuevo coronavirus (2019-nCoV) [Internet]. Ginebra: OMS; 2020. [acceso: 30/01/2020]. Disponible en: https://www.who.int/es/news/item/30-01-2020-statement-on-the-second-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-outbreak-of-novel-coronavirus-(2019-ncov)
2. Nagy A, Alhatlani B. An overview of current COVID-19 vaccine platforms [Internet]. Comput Struct Biotechnol J. 19:2508-17. 2021. DOI: 10.1016/j.csbj.2021.04.061
3. Carlson R, Lutmer H, Beall M, Bolt B, Felton C, Germann L, et al. Precision Vaccinations. Cuba Covid-19 Vaccine. [Internet]. Vax-Before-Travel.2022[acceso: 06/05/2022]. Disponible en: https://www.vax-before-travel.com/vaccines/cuba-covid-19-vaccine
4. Valdes-Balbin Y, Santana-Medero D, Quintero L, Fernández S, Rodriguez L, Sanchez Ramirez B, et al. SARS-CoV-2 RBD-tetanus toxoid conjugate vaccine induces a strong neutralizing immunity in preclinical studies [Internet]. ACS Chem Biol. 2021;16:1223-33. DOI: 10.1101/2021.02.08.430146
5. Griffin JFT. A strategic approach to vaccine development: animal models, monitoring vaccine efficacy, formulation and delivery [Internet]. Adv. Drug Del. Rev. 2002; 54: 851-861. DOI: 10.1016/S0169-409X(02)00072-8
6. Consejo de Estado República de Cuba. Decreto-Ley 31/2021 "De Bienestar Animal". Gaceta Oficial No. 25 Extraordinaria de 10 abril de 2021 [Internet]. La Habana: Ministerio de Justicia; 2021. [acceso: 06/05/202]. Disponible en: https://www.mined.gob.cu/wp-content/uploads/2022/01/goc-2021-ex25-.pdf
7. Consejo de Estado República de Cuba. Decreto 38/2021 "Reglamento del Decreto-Ley de Bienestar Animal". Gaceta Oficial No. 25 Extraordinaria de 10 abril de 2021 [Internet]. La Habana: Ministerio de Justicia; 2021. [acceso: 06/05/202]. Disponible en: https://www.mined.gob.cu/wp-content/uploads/2022/01/goc-2021-ex25-.pdf
8. Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Institute for Laboratory Animal Research. Division on Earth and Life Studies. National Research Council of the National Academies. The National Academies Press. Guide for the Care and Use of Laboratory Animals [Internet]. Eighth Edition. Washington, D.C.: National Academies of Sciences, Engineering, and Medicine; 2011. DOI: 10.17226/12910
9. American Veterinary Medical Association. AVMA Guidelines for the Euthanasia of Animals: 2020 Edition. Schaumburg: American Veterinary Medical Association; 2020. [acceso: 06/05/2022]. Disponible en: https://olaw.nih.gov/policies-laws/avma-guidelines-2020.htm
10. Manenti A, Maggetti M, Casa E, Martinuzzi D, Torelli A, Trombetta CM, et al. Evaluation of SARS-CoV-2 neutralizing antibodies using of a CPE-based colorimetric live virus micro-neutralization assay in human serum samples [Internet]. J Med Virol. 2020; 1-9. DOI: 10.1002/jmv.25986
11. González-Sosa N, Oliva-Hernández R, Blanco-de Armas M, Infante-Bouzac J, Enríquez-Puertas J, Rodríguez-Salgueiro S, et al. Infectividad del coronavirus tipo 2 del síndrome respiratorio agudo severo en hámster Sirio Dorado como modelo para ensayos de inmunogenicidad y eficacia de biomoléculas y candidatos vacunales [Internet]. Vaccimonitor. 2024 [acceso: 17/12/2024];33:e153324. Disponible en: https://vaccimonitor.finlay.edu.cu/index.php/vaccimonitor/article-/view/9218
12. Matute-Bello G, Downey G, Moore BB, Groshong SD, Matthay MA, Slutsky AS, et al. Acute Lung Injury in Animals Study Group. An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals [Internet]. Am J Respir Cell Mol Biol. 2011; 44(5):725-38. DOI: 10.1165/rcmb.2009-0210ST
13. Li C, Chen YX, Liu FF, Lee AC, Zhao Y, Ye ZH, et al. Absence of Vaccine-enhanced Disease with Unexpected Positive Protection Against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by Inactivated Vaccine Given Within 3 Days of Virus Challenge in Syrian Hamster Model [Internet]. Clin Infect Dis. 2021;73(3): e719-e734. DOI: 10.1093/cid/ciab083
14. Molina-Cuevas V, Ravelo-Calzado Y, Zamora-Rodríguez Z, Noa-Puig M, Valle-Clara M, Pérez-Guerra, Y, et al. Efectos en ratas de los alcoholes de cera de abejas (D-002) sobre la colitis ulcerativa inducida por sulfato de dextrano y etanol [Internet]. Revista Peruana de Medicina Experimental y Salud Pública. 2017; 34(2):176-182. DOI: 10.17843/rpmesp.2017.342.2369
15. R-Biopharm AG. RIDA®GENE SARS-CoV-2 REF. PG6820. Alemania, Darmstadt; 2020. [acceso: 17/12/2024]. Disponible en: https://clinical.r-biopharm.com/wp-content/uploads/2020/06/pg6820_ridagene_sars-cov-2_2020-10-28_en.pdf
16. Nalla AK, Casto AM, Huang M-LW, Perchetti GA, Sampoleo R, Shrestha L, et al. Comparative performance of SARS-CoV-2 detection assays using seven different primer- probe sets and one assay kit [Internet]. J Clin Microbiol. 2020; 58: e00557-20. DOI: 10.1128/JCM.00557-20
17. Sahoo M, Huang C, Sibai M, Solis D, Pinsky B. Harmonization of SARS-CoV-2 reverse transcription quantitative PCR tests to the first WHO international standard for SARS-CoV-2 RNA [Internet]. Journal of Clinical Virology. 2022;154. DOI: 10.1016/j.jcv.2022.105242.105242
18. Bentley EM, Le Duff Y, Ham C, Cherry C, Mattiuzzo G, Fryer J, et al. Collaborative Study for the Establishment of the Second WHO International Standard for SARS-CoV-2 RNA [Internet]. Geneva: World Health Organization Expert Committee on Biological Standardization. WHO/BS/2023.2459; 2023. [acceso: 17/12/2024]. Disponible en: https://www.who.int/publications/m/item/who-bs-2023.2459
19. Chan JF, Zhang AJ, Yuan S, Poon VK, Chan CC, Lee AC, et al. Simulation of the Clinical and Pathological Manifestations of Coronavirus Disease 2019 (COVID-19) in a Golden Syrian Hamster Model: Implications for Disease Pathogenesis and Transmissibility [Internet]. Clin Infect Dis. 2020;71(9):2428-2446. DOI: 10.1093/cid/ciaa325
20. Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus [Internet]. J Virol. 2020; 94(7): e00127-20. DOI: 10.1128/JVI.00127-20
21. Tan CW, Chia WN, Qin X, Liu P, Chen MI, Tiu C, et al. A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein-protein interaction [Internet]. Nat Biotechnol. 2020; 38(9):1073-8. DOI: 10.1038/s41587-020-0631-z
22. Griffin BD, Warner BM, Chan M, Valcourt E, Tailor N, Banadyga L, et al. Host parameters and mode of infection influence outcome in SARS-CoV-2-infected hamsters [Internet]. iScience. 2021;24(12):103530. DOI: 10.1016/j.isci.2021.103530
23. Yuan L, Zhu H, Zhou M, Ma J, Chen R, Chen Y, et al. . Gender associates with both susceptibility to infection and pathogenesis of SARS-CoV-2 in Syrian hamster [Internet]. Signal Transduct Target Ther. 2021;6(1):136. DOI: 10.1038/s41392-021-00552-0
24. Cuenca-Pardo J, Ramos-Gallardo G, Vélez-Benítez E, Álvarez-Díaz Carlos de J, Bucio-Duarte J, Iribarren-Moreno R, et al. La importancia de reducir la carga viral para disminuir el riesgo de contagio por COVID-19 [Internet]. Cir Plast. 2020;30(2):78-93. DOI:10.35366/97674
25. Sia SF, Yan LM, Chin AWH, Fung K, Choy KT, Wong AYL, et al. Pathogenesis and transmission of SARS-CoV-2 in golden hamsters. Nature. 2020;583(7818): 834-838. DOI: 10.1038/s41586-020-2342-5
26. Lee AC, Zhang AJ, Chan JF, Li C, Fan Z, Liu F, et al. Oral SARS-CoV-2 Inoculation Establishes Subclinical Respiratory Infection with Virus Shedding in Golden Syrian Hamsters [Internet]. Cell Rep Med. 2020;1(7):100121. DOI: 10.1016/j.xcrm
27. Lin YJ, Lin MY, Chuang YS, Liu LT, Kuo TY, Chen C, et al Protection of hamsters challenged with SARS-CoV-2 after two doses of MVC-COV1901 vaccine followed by a single intranasal booster with nanoemulsion adjuvanted S-2P vaccine. Sci Rep. 2022;12(1):11369. DOI: 10.1038/s41598-022-15238-y
28. Vega-de LoPresti Y, Montilva-Gutiérrez E, Valenzuela-Vegas A, Salazar-Pérez KE, Paredes-Manodanda AS, Alvarado-García AJ, et al. Upper respiratory tract viral load quantification in COVID-19 patients at hospital admission and its association with disease severity [Internet]. Gac Med Mex. 2022;158(5):320-326. DOI: 10.24875/GMM.M22000700
29. O'Donnell KL, Clancy CS, Griffin AJ, Shifflett K, Gourdine T, Thomas T, et al. Optimization of Single-Dose VSV-Based COVID-19 Vaccination in Hamsters. Frontiers in Immunology. 2022; 12:788235 DOI: 10.3389/fimmu.2021.788235
30. Yahalom-Ronen Y, Tamir H, Melamed S, Politi B, Shifman O, Achdout H, et al. A single dose of recombinant VSV-?G-spike vaccine provides protection against SARS-CoV-2 challenge [Internet]. Nat Commun. 2020;11(1):6402. DOI: 10.1038/s41467-020-20228-7
31. Wussow F, Kha M, Faircloth K, Nguyen VH, Iniguez A, Martinez J, et al. COH04S1 and beta sequence-modified vaccine protect hamsters from SARS-CoV-2 variants [Internet]. iScience. 2022;25(6):104457. DOI: 10.1016/j.isci.2022.104457
32. Jefferson T, Spencer EA, Brassey J, Heneghan C. Viral Cultures for Coronavirus Disease 2019 Infectivity Assessment: A Systematic Review[Internet]. Clin Infect Dis. 2021;73(11):e3884-e3899. DOI: 10.1093/cid/ciaa1764
33. Jiang RD, Liu MQ, Chen Y, Shan C, Zhou YW, Shen XR, et al. Pathogenesis of SARS-CoV-2 in Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2 [Internet]. Cell. 2020;182(1):50-58. DOI: 10.1016/j.cell.2020.05.027
34. Chandrashekar A, Liu J, Martinot AJ, McMahan K, Mercado NB, Peter L, et al. SARS-CoV-2 infection protects against rechallenge in rhesus macaques [Internet]. Science. 2020;369(6505):812-17. DOI: 10.1126/science.abc4776
35. Muñoz-Fontela C, Dowling WE, Funnell SGP, Gsell PS, Riveros-Balta AX, Albrecht RA, et al. Animal models for COVID-19 [Internet]. Nature. 2020;586(7830):509-15. DOI: 10.1038/s41586-020-2787-6
36. Imai M, Iwatsuki-Horimoto K, Hatta M, Loeber S, Halfmann PJ, Nakajima N, et al. Syrian hamsters as a small animal model for SARS-CoV-2 infection and countermeasure development [Internet]. Proc Natl Acad Sci USA. 2020;117(28):16587-95. DOI: 10.1073/pnas.2009799117
37. Rosenke K, Meade-White K, Letko M, Clancy C, Hansen F, Liu Y, et al. Defining the Syrian hamster as a highly susceptible preclinical model for SARS-CoV-2 infection [Internet]. Emerg Microbes Infect. 2020;9(1):2673-84. DOI:10.1080/22221751.2020.1858177
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Copyright (c) 2025 Nibaldo Luis González Sosa, Reynaldo Oliva Hernández, Madeline Blanco de Armas, Mildrey Fariñas Medina, Juan Francisco Infante Bouzac, Yanet Climent Ruiz, Sonsire Fernández Castillo, Liuber Yans Machado Zaldívar, Enrique Noa Romero, Yuliet Sotes Sarguero, Darcy Núñez Martínez, Sandra Rodríguez Salgueiro, Mireida Rodríguez Acosta, Yisabel Aranguren Mazorra, Otto Cruz Sui, Marta Dubed Echevarría, Dagmar García Rivera
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