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Cynomolgus Macaque Model for COVID-19 Delta Variant

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With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, which are randomly mutated, the dominant strains in regions are changing globally. The development of preclinical animal models is imperative to validate vaccines and therapeutics against SARS-CoV-2 variants. The objective of this study was to develop a non-human primate (NHP) model for SARS-CoV-2 Delta variant infection. Cynomolgus macaques infected with Delta variants showed infectious viruses and viral RNA in the upper (nasal and throat) and lower respiratory (lung) tracts during the acute phase of infection. After 3 days of infection, lesions consistent with diffuse alveolar damage were observed in the lungs. For cellular immune responses, all macaques displayed transient lymphopenia and neutrophilia in the early stages of infection. SARS-CoV-2 Delta variant spike protein-specific IgM, IgG, and IgA levels were significantly increased in the plasma of these animals 14 days after infection. This new NHP Delta variant infection model can be used for comparative analysis of the difference in severity between SARS-CoV-2 variants of concern and may be useful in the efficacy evaluation of vaccines and universal therapeutic drugs for mutations.

Abstract

With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, which are randomly mutated, the dominant strains in regions are changing globally. The development of preclinical animal models is imperative to validate vaccines and therapeutics against SARS-CoV-2 variants. The objective of this study was to develop a non-human primate (NHP) model for SARS-CoV-2 Delta variant infection. Cynomolgus macaques infected with Delta variants showed infectious viruses and viral RNA in the upper (nasal and throat) and lower respiratory (lung) tracts during the acute phase of infection. After 3 days of infection, lesions consistent with diffuse alveolar damage were observed in the lungs. For cellular immune responses, all macaques displayed transient lymphopenia and neutrophilia in the early stages of infection. SARS-CoV-2 Delta variant spike protein-specific IgM, IgG, and IgA levels were significantly increased in the plasma of these animals 14 days after infection. This new NHP Delta variant infection model can be used for comparative analysis of the difference in severity between SARS-CoV-2 variants of concern and may be useful in the efficacy evaluation of vaccines and universal therapeutic drugs for mutations.

참고문헌 (18)

  1. Huang C, "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China", Lancet, 395, pp.497~506 (2020)
  2. Radvak P, "SARS-CoV-2 B. 1. 1. 7(alpha)and B. 1. 351(beta)variants induce pathogenic patterns in K18-hACE2 transgenic mice distinct from early strains", Nat Commun, 12, pp.6559~ (2021)
  3. Chiuppesi F, "Development of a multi-antigenic SARS-CoV-2 vaccine candidate using a synthetic poxvirus platform", Nat Commun, 11, pp.6121~ (2020)
  4. Ryan KA, "Dose-dependent response to infection with SARS-CoV-2 in the ferret model and evidence of protective immunity", Nat Commun, 12, pp.81~ (2021)
  5. Vogel AB, "BNT162b vaccines protect rhesus macaques from SARS-CoV-2", Nature, 592, pp.283~289 (2021)
  6. Corbett KS, "Evaluation of the mrna-1273 vaccine against sars-cov-2 in nonhuman primates", N Engl J Med, 383, pp.1544~1555 (2020)
  7. Mercado NB, "Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques", Nature, 586, pp.583~588 (2020)
  8. Kim G, "Germinal centerinduced immunity is correlated with protection against SARS-CoV-2 reinfection but not lung damage", J Infect Dis, 224, pp.1861~1872 (2021)
  9. Koo BS, "Transient lymphopenia and interstitial pneumonia with endotheliitis in SARS-CoV-2-infected macaques", J Infect Dis, 222, pp.1596~1600 (2020)
  10. Hong SH, "Immunization with RBD-P2 and N protects against SARS-CoV-2 in nonhuman primates", Sci Adv, 7, pp.eabg7156~ (2021)
  11. Kim C, "A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein", Nat Commun, 12, pp.288~ (2021)
  12. Seo YB, "Soluble spike DNA vaccine provides long-term protective immunity against SARS-CoV-2 in mice and nonhuman primates", Vaccines(Basel), 9, pp.307~ (2021)
  13. Chu DK, "Molecular diagnosis of a novel coronavirus(2019-nCoV)causing an outbreak of pneumonia", Clin Chem, 66, pp.549~555 (2020)
  14. Tai W, "Characterization of the receptor-binding domain(RBD)of 2019 novel coronavirus : implication for development of RBD protein as a viral attachment inhibitor and vaccine", Cell Mol Immunol, 17, pp.613~620 (2020)
  15. Wang Y, "Transmission, viral kinetics and clinical characteristics of the emergent SARS-CoV-2 Delta VOC in Guangzhou, China", EClinicalMedicine, 40, pp.101129~ (2021)
  16. Shuai H, "Attenuated replication and pathogenicity of SARS-CoV-2 B. 1. 1. 529 Omicron", Nature, 603, pp.693~699 (2022)
  17. Cheng QR, "Chest CT features of children infected by B. 1. 617. 2(Delta)variant of COVID-19", World J Pediatr, 18, pp.37~42 (2022)
  18. Zheng H, "Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques : a nonhuman primate model of COVID-19progression", PLoS Pathog, 16, pp.e1008949~ (2020)

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