پاسخ‌های ایمنی علیه ویروس‌های خانواده‌ی کرونا و راهبردهای ساخت واکسن

عندلیب, علیرضا

doi:10.22122/jims.v38i579.12899

پاسخ‌های ایمنی علیه ویروس‌های خانواده‌ی کرونا و راهبردهای ساخت واکسن

نوع مقاله : مقاله مروری

نویسنده

علیرضا عندلیب

استاد، گروه ایمنی‌شناسی، دانشکده‌ی پزشکی، دانشگاه علوم پزشکی اصفهان، اصفهان، ایران

10.22122/jims.v38i579.12899

چکیده

کرونا ویروس‌های تنفسی پاتوژن‌های بومی حیوانات است که در انسان مجاری تنفسی فوقانی را عفونی می‌نماید. التهاب شدید ریوی ناشی از به هم خوردن تنظیم سیتوکین‌ها در بیماران Severe acute respiratory syndrome (SARS) نظیر افزایش سطح Tumor necrosis factor alpha (TNFα)، پروتئین IPLO، Interleukin-6 (IL-6) و IL-8 در خون است که با عواقب ناخوشایند همراه می‌باشد. لنفوسیت‌های T اجرایی اختصاصی علیه ویروس‌ها، سیتوکین‌های ضروری شامل IL-2، TNFα و Interferon-gamma (IFN-γ) و کموکاین‌های 9، 10 و 11 (CXCL-9, 10, 11) مولکول‌های سیتوتوکسیک (نظیر پرفورین و گرانزیم B) تولید می‌کند. بیماران مبتلا به مرحله‌ی حاد تنفسی با خانواده‌ی ویروس‌های کرونا با لوکوپنی و لنفوپنی شدید همراه است که در این موارد، کاهش شدید لنفوسیت‌های TCD4 و TCD8 در 90-80 درصد بیماران مشاهده می‌شود. در وضعیت حاد بستری در بیمارستان، افزایش سیتوکین‌های التهابی IL-2، IL-7، IL-10، Granulocyte colony-stimulating factor (G-CSF)، Interferon-γ-inducible protein 10 (IP-10)، Monocyte chemoattractant protein-1 (MCP-1)، Macrophage inflammatory protein 1 alpha (MIP-1A) و TNFα شباهت زیادی با الگوی طوفان سیتوکینی و لنفوپنی، سپسیس ویرال، التهاب و آسیب ریه و به دنبال آن، عواقب پنومونی، سندرم دیسترس تنفسی حاد، شوک، از دست رفتن عملکرد تنفسی و سایر اعضا و در نهایت، مرگ منجر خواهد شد. چگونگی ایجاد آسیب توسط پاتوژن در افراد، تصویر روشن‌تری برای ایمنولوژیست‌ها فراهم نموده است؛ در حالی که بیشتر افراد آلوده به ویروس، تنها دارای علایم متوسط یا بدون علامت می‌شوند، اما عفونت ویروسی در اقلیتی از مبتلایان عوارض حاد ایجاد می‌نماید. وجود ارتباط در همبستگی بین مصونیت‌بخشی و ایجاد حفاظت دراز مدت ایمنی در افراد بستری با Corona virus disease-19 (COVID-19) راهی برای طراحی واکسن‌های مؤثر و یا راه‌های درمانی مؤثر برای مقابله با شیوع ویروس کرونا باز نموده است.

کلیدواژه‌ها

عنوان مقاله [English]

Immune Responses to Corona Family Viruses and Vaccine Strategies

نویسنده [English]

Alireza Andalib

Professor, Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

چکیده [English]

Corona respiratory viruses are native animal pathogens that infect upper respiratory tract in humans. Severe pulmonary inflammation caused by disruption of the regulation of cytokines in patients with severe acute respiratory syndrome (SARS), such as elevated levels of tumor necrosis factor alpha (TNFα), IPLO protein, interleukin 6 (IL-6), and IL-8 in the blood, with undesirable consequences. Specific executive T lymphocytes against viruses produce essential cytokines including IL-2, TNF-α, interferon-gamma (IFNγ), and the chemokines such CXCL-9, 10, and 11, and cytotoxic molecules such as perforin and granzyme B. Acute respiratory phase causing by corona virus disease is associated with severe lymphopenia in peripheral blood accompanied with decreased TCD4 and TCD8 in 80% to 90% of patients. Acute inflammatory cytokines including IL-2, IL-7, IL-10, granulocyte colony-stimulating factor (G-CSF), interferon-γ-inducible protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein 1 alpha (MIP-1A), and TNFα have been reported to be elevated in acute hospitalized patients with lymphopenia and sepsis viral. In addition, inflammation, lung injury, pneumonia, acute respiratory distress syndrome, loss of respiratory function and other organs, and eventually death are the consequences of the pathogenesis of the virus responsiveness by immune system. How pathogens are harmed in humans has provided a clear picture for interrupt in processing steps by immunologists. While most people infected with the virus have only moderate or asymptomatic symptoms, but a minority have experienced acute complications. Investigating the correlation between safety protection and long-term safety protection in hospitalized patients with corona virus disease-19 (COVID-19) has opened a way to design effective vaccines or effective therapies to counter the prevalence of coronavirus and disease.

کلیدواژه‌ها [English]

COVID-19
Cytokines
Immune system

مراجع

Siddell SG, Ziebuhr J, Snijder EJ. Coronaviruses, toroviruses, and arteriviruses. In Mahy BWJ, Ter Meulen V, editors, Topley and Wilson's microbiology and microbial infections. London, UK: Hodder Arnold; 2005. p. 823-856.
Weiss SR, Navas-Martin S. Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol Mol Biol Rev 2005; 69(4): 635-64.
Rota PA, Oberste MS, Monroe SS, Nix WA, Campagnoli R, Icenogle JP, et al. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 2003; 300(5624): 1394-9.
van BS, de GM, Lauber C, Bestebroer TM, Raj VS, Zaki AM, et al. Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. mBio 2012; 3(6).
Zaki AM, van BS, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 2012; 367(19): 1814-20.
Peiris JS, Guan Y, Yuen KY. Severe acute respiratory syndrome. Nat Med 2004; 10(12 Suppl): S88-S97.
Kong SL, Chui P, Lim B, Salto-Tellez M. Elucidating the molecular physiopathology of acute respiratory distress syndrome in severe acute respiratory syndrome patients. Virus Res 2009; 145(2): 260-9.
Wong CK, Lam CW, Wu AK, Ip WK, Lee NL, Chan IH, et al. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin Exp Immunol 2004; 136(1): 95-103.
Baas T, Taubenberger JK, Chong PY, Chui P, Katze MG. SARS-CoV virus-host interactions and comparative etiologies of acute respiratory distress syndrome as determined by transcriptional and cytokine profiling of formalin-fixed paraffin-embedded tissues. J Interferon Cytokine Res 2006; 26(5): 309-17.
Chen J, Lau YF, Lamirande EW, Paddock CD, Bartlett JH, Zaki SR, et al. Cellular immune responses to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in senescent BALB/c mice: CD4+ T cells are important in control of SARS-CoV infection. J Virol 2010; 84(3): 1289-301.
Belz GT, Smith CM, Kleinert L, Reading P, Brooks A, Shortman K, et al. Distinct migrating and nonmigrating dendritic cell populations are involved in MHC class I-restricted antigen presentation after lung infection with virus. Proc Natl Acad Sci U S A 2004; 101(23): 8670-5.
Norbury CC, Malide D, Gibbs JS, Bennink JR, Yewdell JW. Visualizing priming of virus-specific CD8+ T cells by infected dendritic cells in vivo. Nat Immunol 2002; 3(3): 265-71.
Wherry EJ, Ahmed R. Memory CD8 T-cell differentiation during viral infection. J Virol 2004; 78(11): 5535-45.
Saha B, Jyothi PS, Chandrasekar B, Nandi D. Gene modulation and immunoregulatory roles of interferon gamma. Cytokine 2010; 50(1): 1-14.
Cerwenka A, Morgan TM, Dutton RW. Naive, effector, and memory CD8 T cells in protection against pulmonary influenza virus infection: homing properties rather than initial frequencies are crucial. J Immunol 1999; 163(10): 5535-43.
Wong RS, Wu A, To KF, Lee N, Lam CW, Wong CK, et al. Haematological manifestations in patients with severe acute respiratory syndrome: retrospective analysis. BMJ 2003; 326(7403): 1358-62.
Li T, Qiu Z, Zhang L, Han Y, He W, Liu Z, et al. Significant changes of peripheral T lymphocyte subsets in patients with severe acute respiratory syndrome. J Infect Dis 2004; 189(4): 648-51.
Cai C, Zeng X, Ou AH, Huang Y, Zhang X. Study on T cell subsets and their activated molecules from the convalescent SARS patients during two follow-up surveys. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2004; 20(3): 322-4. [In Chinese].
Yu XY, Zhang YC, Han CW, Wang P, Xue XJ, Cong YL. Change of T lymphocyte and its activated subsets in SARS patients. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2003; 25(5): 542-6. [In Chinese].
Cameron MJ, Bermejo-Martin JF, Danesh A, Muller MP, Kelvin DJ. Human immunopathogenesis of severe acute respiratory syndrome (SARS). Virus Res 2008; 133(1): 13-9.
Lu H, Zhao Y, Zhang J, Wang Y, Li W, Zhu X, et al. Date of origin of the SARS coronavirus strains. BMC Infect Dis 2004; 4: 3.
Vega VB, Ruan Y, Liu J, Lee WH, Wei CL, Se-Thoe SY, et al. Mutational dynamics of the SARS coronavirus in cell culture and human populations isolated in 2003. BMC Infect Dis 2004; 4: 32.
Cameron MJ, Kelvin AA, Leon AJ, Cameron CM, Ran L, Xu L, et al. Lack of innate interferon responses during SARS coronavirus infection in a vaccination and reinfection ferret model. PLoS One 2012; 7(9): e45842.
Cameron MJ, Ran L, Xu L, Danesh A, Bermejo-Martin JF, Cameron CM, et al. Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome. J Virol 2007; 81(16): 8692-706.
Weingartl H, Czub M, Czub S, Neufeld J, Marszal P, Gren J, et al. Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets. J Virol 2004; 78(22): 12672-6.
Spruth M, Kistner O, Savidis-Dacho H, Hitter E, Crowe B, Gerencer M, et al. A double-inactivated whole virus candidate SARS coronavirus vaccine stimulates neutralising and protective antibody responses. Vaccine 2006; 24(5): 652-61.
Chu YK, Ali GD, Jia F, Li Q, Kelvin D, Couch RC, et al. The SARS-CoV ferret model in an infection-challenge study. Virology 2008; 374(1): 151-63.
Martin JE, Louder MK, Holman LA, Gordon IJ, Enama ME, Larkin BD, et al. A SARS DNA vaccine induces neutralizing antibody and cellular immune responses in healthy adults in a Phase I clinical trial. Vaccine 2008; 26(50): 6338-43.
Nicholls JM, Poon LL, Lee KC, Ng WF, Lai ST, Leung CY, et al. Lung pathology of fatal severe acute respiratory syndrome. Lancet 2003; 361(9371): 1773-8.
Prompetchara E, Ketloy C, Palaga T. Immune responses in COVID-19 and potential vaccines: Lessons learned from SARS and MERS epidemic. Asian Pac J Allergy Immunol 2020; 38(1): 1-9.
Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579(7798): 270-3.
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med 2020; 382(8): 727-33.
Perlman S, Dandekar AA. Immunopathogenesis of coronavirus infections: implications for SARS. Nat Rev Immunol 2005; 5(12): 917-27.
de WE, van DN, Falzarano D, Munster VJ. SARS and MERS: recent insights into emerging coronaviruses. Nat Rev Microbiol 2016; 14(8): 523-34.
Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 2017; 39(5): 529-39.
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395(10223): 497-506.
Liu W, Fontanet A, Zhang PH, Zhan L, Xin ZT, Baril L, et al. Two-year prospective study of the humoral immune response of patients with severe acute respiratory syndrome. J Infect Dis 2006; 193(6): 792-5.
Liu WJ, Zhao M, Liu K, Xu K, Wong G, Tan W, et al. T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV. Antiviral Res 2017; 137: 82-92.