Immunological Approaches and Different Strategies for Vaccine Development against SARS-COV-2

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Muhammed Babakir-Mina


Globally, SARS-CoV-2 outbreak is considered as pandemic viral infection by the World Health Organization (WHO). In the immunological response aspect, a very limited understanding has been progressed, mainly innate and adaptive immunity responses toward the virus. SARS-COV-2 causes severe respiratory disease and sometimes ended with the death. The body of the patients has ability to develop the immunity to cure the patient and more importantly both humoral and cellular immunity have studied against SARS-COV-2. There are different immune responses against the viral infection as it has seen in other previous diseases such as SARS-COV and MESR. On the base on immune response detected in recovered patients, scientists have started to develop the vaccines. Moreover, there are different strategies that used by researchers and pharmacological companies to develop vaccines including attenuated or killed viruses, RNA of a spike protein, and vector expressing a particular protein of the virus. The common antibodies have detected to work against SARS-COV-2 in sera of infected or recovered patients are immunoglobin G ( IgG) and immunoglobin M (IgM). The sera of patients recovered from COVID-19, after tittering of immunoglobulins (IgG titer) can be used for either treatment of disease or prophylaxis of infection by SARS-COV-2. This study gives an update on the current immunological approaches and vaccination strategies for the emerging SARS-COV-2, and discusses the challenges and hurdles to overcome for developing efficacious vaccines against this dangerous pathogen.


SARS-COV-2, immunity, IgG, IgM, vaccines, Serum therapy


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[1] T. BRACIALE, J. SUN, T. KIM, “Regulating the adaptive immune response to respiratory virus infection,” Nature Reviews Immunology, 12, pp. 295-305, 2012.
[2] DANDEKAR, S. PERLMAN, “Immunopathogenesis of coronavirus infections: implications for SARS,” Nature reviews immunology, 5, pp. 917-927, 2005.
[3] G. RADICIONI, R.CAO, J. CARPENTER, A. FORD, T. WANG, Y. LI, et al., “The innate immune properties of airway mucosal surfaces are regulated by dynamic interactions between mucins and interacting proteins: the mucin interactome,” Mucosal immunology, 9, pp. 1442-1454, 2016.
[4] IWASAKI, , E. FOXMAN, R. MOLONY, “ Early local immune defences in the respiratory tract’” Nature Reviews Immunology, 17, pp. 7, 2015.
[5] LAMBRECHT, H. HAMMAD, “The airway epithelium in asthma. Nature medicine,” 18, pp.684, 2012.
[6] JUNCADELLA, A. KADL, A. SHARMA, Y. SHIM, A. HOCHREITER-HUFFORD, L. BORISH, et al., “Apoptotic cell clearance by bronchial epithelial cells critically influences airway inflammation,” Nature, 493, pp. 547-551, 2013.
[7] IWASAKI, E. FOXMAN, R. MOLONY, “Early local immune defences in the respiratory tract,” Nature Reviews Immunology, 17, pp. 7, 2017.
[8] T. BRACIALE, J. SUN, T. KIM, "Regulating the adaptive immune response to respiratory virus infection," Nature Reviews Immunology, 12, pp. 295-30, 2012.
[9] S. PERLMAN, J. NETLAND, "Coronaviruses post-SARS: update on replication and pathogenesis. Nature reviews microbiology, 7, pp. 439-450, 2009.
[10] WHO, "Coronavirus disease (COVID-19) advice for the public: when and how to use masks. World Health Organization," 2020.
[11] G. LI, Y. FAN, Y. LAI, T. HAN, Z. LI, P. ZHOU, et al., "Coronavirus infections and immune responses," Journal of medical virology, 92, pp. 424-432, 2020.
[12] P. ZHOU, X. YANG, X. WANG, B. HU, L. ZHANG, W. ZHANG, et al., "A pneumonia outbreak associated with a new coronavirus of probable bat origin," Nature, 579, pp. 270-273, 2020.
[13] A. DANDEKAR, S. PERLMAN, "Immunopathogenesis of coronavirus infections: implications for SARS," Nature reviews immunology, 5, pp. 917-927. 2005.
[14] N. ZHU, D. ZHANG, W. WANG, X. LI, B. YANG, J. SONG, et al. A novel coronavirus from patients with pneumonia in China," New England Journal of Medicine, 2020.
[15] T. TANIGUCHI, A. TAKAOKA, "A weak signal for strong responses: interferon-alpha/beta revisited," Nature reviews Molecular cell biology, 2, pp. 378-386, 2001.
[16] O. TAKEUCHI, S. AKIRA, "MDA5/RIG-I and virus recognition," Current opinion in immunology, 20, pp. 17-22, 2008.
[17] R. WELSH, S. WAGGONER, "NK cells controlling virus-specific T cells: Rheostats for acute vs. persistent infections," Virology, 435, pp. 37-45, 2013.
[18] R. STEINMAN, J. BANCHEREAU, "Taking dendritic cells into medicine," Nature, 449, pp. 419-426, 2007.
[19] M. NOURI-SHIRAZI, E. GUINET, "Exposure to nicotine adversely affects the dendritic cell system and compromises host response to vaccination," The Journal of Immunology, 188, pp. 2359-2370, 2012.
[20] C. KAEWRAEMRUAEN, P. RITPRAJAK, N. HIRANKARN, "Dendritic cells as key players in systemic lupus erythematosus," Asian Pacific journal of allergy, 2019.
[21] L. WU, V. KEWALRAMANI, "Dendritic-cell interactions with HIV: infection and viral dissemination," Nature reviews immunology, 6, pp. 859-868, 2006.
[22] LE BON, D. TOUGH, “Links between innate and adaptive immunity via type I interferon,” Current opinion in immunology, 14, pp. 432-436, 2002.
[23] W. LI, M. MOORE, N. VASILIEVA, J. SUI, S. WONGK, M. BERNE, et al., “Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus,” Nature, 426, pp. 450-454, 2003.
[24] GLOWACKA, , S. BERTRAM, , M. MÜLLER, P. ALLEN, E. SOILLEUX, S. PFEFFERLESTEFFEN, et al., “Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response,” Journal of virology, 85, pp. 4122-4134, 2011.
[25] W. LIU, M. ZHAO, K. LIU, K. XU, G. WONG, W. TAN, et al., “T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV,” Antiviral research, 137, pp. 82-92, 2017.
[26] M. CHENG, C. CHAN, R. CHEUNG, R. BIKKAVILLI, Q. ZHAO, S. AU, et al., “Cross-reactivity of antibody against SARS-coronavirus nucleocapsid protein with IL-11,” Biochem Biophys Res Commun, 338, pp. 1654-60, 2005.
[27] Y. TAN, P. GOH, B. FIELDING, S. S HEN, C. CHOU, J. FU, et al, “Profiles of antibody responses against severe acute respiratory syndrome coronavirus recombinant proteins and their potential use as diagnostic markers,” Clinical Diagnostic Laboratory Immunolog, 11, pp. 362-371, 2004.
[28] W. CAO, W. LIU, P. ZHANG, F. ZHANG, J. RICHARDUS, “Disappearance of antibodies to SARS-associated coronavirus after recovery,” N Engl J Med, 357, pp. 1162-3, 2007.
[29] WALLS, M. TORTORICI, B. FRENZ, J. SNIJDERLI, F. REY, F. DIMAIO, et al., “Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy,” Nature structural molecular biology, 23, pp. 899, 2016.
[30] WALLS, X. XIONG, Y. PARK, M. TORTORICI, J. SNIJDER, J. QUISPE, et al., “Unexpected receptor functional mimicry elucidates activation of coronavirus fusion,” Cell, 176, pp. 1026-1039, 2019.
[31] Y. WATANABE, J. ALLEN, D. WRAPP, J. MCLELLAN, M. CRISPIN, “Site-specific glycan analysis of the SARS-CoV-2 spike,” Science, 2020.
[32] L. BAO, W. DENG, H. GAO, C. XIAO, J. LIU, J. XUE, et al., "Rei nfection could not occur in SARS-CoV-2 infected rhesus macaques," BioRxiv, 2020.
[33] H. CHEN, Susceptibility of ferrets, cats, dogs, and different domestic animals to SARS-coronavirus-2," BioRxiv, 2020.
[34] V. MUNSTER, F. FELDMANN, B. WILLIAMSON, N. VAN DOREMALEN, L. PÉREZ-PÉREZ, J. SCHULZ, ,et al., "Respiratory disease and virus shedding in rhesus macaques inoculated with SARS-CoV-2," BioRxiv, 2020.
[35] J. ZHAO, Q. YUAN, H. WANG, W. LIU, X. LIAO, Y. SU, et al., "Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019," Clinical Infectious Diseases, 2020.
[36] W. LIU, M. ZHAO, K. LIU, K. XU, G. WONG, W. TAN, et al., "T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV," Antiviral research, 137, pp. 82-92, 2017.
[37] I. HUNG, K. TO, C. LEE, K. LEE, K. CHAN, W. YAN, R. LIU, et al., "Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection," Clinical Infectious Diseases, 52, pp. 447-456, 2011.
[38] M. HOFFMANN, H. KLEINE-WEBER, S. SCHROEDER, N. KRÜGER, , T. HERRLER, S. ERICHSEN, "SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor," Cell, 2020.
[39] B. KELLEY, "Developing therapeutic monoclonal antibodies at pandemic pace," Nature biotechnolog, 38, pp. 540-545, 2020.
[40] A. CASADEVALL, L. PIROFSKI, "The convalescent sera option for containing COVID-19," The Journal of clinical investigation, 130, pp. 1545-1548, 2020.
[41] I. THEVARAJAN, T. NGUYEN, M. KOUTSAKOS, J. DRUCE, CALY, L., C. VAN DE SANDT, et al., "Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19," Nature medicine, 26, pp. 453-455, 2020.
[42] FDA, "Recommendations for investigational COVID-19 convalescent plasma. accessed April 9, 2020, 2020.
[43] K. Chen, G. Magri, E. Grasset, "Rethinking mucosal antibody responses: IgM, IgG and IgD join IgA," Nat Rev Immunol, 20, pp. 427–441, 2020.
[44] Z. Eugenia, F. Yvonne, C. Zi, M. Natalieei, "A Dynamic Immune Response Shapes COVID-19 Progression,' Cell Host and Microbe, 27(6), pp. 879-82, 2020.
[45] L. Guo, “Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19)," Clinical Infectious Diseases, 2020.
[46] M. Nisreen, “SARS-CoV-2 Specific Antibody Responses in COVID-19 Patients," preprint (Infectious Diseases (except HIV/AIDS), 2020.
[47] W. Liu, “Evaluation of Nucleocapsid and Spike Protein-Based ELISAs for Detecting Antibodies against SARS-CoV-2," Journal of Clinical Microbiology, 2020.
[48] A. Padoan, “IgA-Ab Response to Spike Glycoprotein of SARS-CoV-2 in Patients with COVID-19: A Longitudinal Study," Clinica Chimica Acta 507, pp. 164–66, 2020.
[49] S. Sanche, YT. Lin, C. Xu, E. Romero‑Severson, N. Hengartner, R. Ke, "Early release‑High contagiousness and rapid spread of severe acute respiratory syndrome coronavirus," Emerging Infect Dis J, 2020.
[50] MI. Anasir, CL. Poh, "Structural Vaccinology for Viral Vaccine Design,' Front Microbiol, 2019.
[51] K. Dhama, K. Sharun, R. Tiwari, M. Dadar, S. Malik, K. Singh, et al., COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics," Hum Vaccin Immunother, 2020.
[52] WHO, "Draft landscape of COVID-19 candidate vaccines," World Health Organisation, 2020.
[53] W. Ning, S. Jian, J. Shibo, D. Lanying, "Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses," Frontiers in Microbiology, 2020.
[54] T. Le, A. Thanh, K. Zacharias, R. Arun, G. Raú, S. Tollefsen, "The COVID-19 vaccine development landscape," Nature Reviews Drug Discovery, 19(5), pp. 305–306, 2020.
[55] V. Gupta, T. Tabiin, K. Sun, A. Chandrashekaran, A. Anwar, K. Yang, et al., SARS coronavirus nucleocapsid immunodominant T-cell epitope cluster is common to both exogenous recombinant and endogenous DNA-encoded immunogens," Virology, 347(1), pp. 127–139. 2006.
[56] V. Baruah, S. Bose, "Immunoinformatics-aided identification of T cell and B cell epitopes in the surface glycoprotein of 2019-nCoV," J Med Virol, 495–500, 2020.
[57] NIH Clinical Trial of Investigational Vaccine for COVID‑19 Begins | NIH: National Institute of Allergy and Infectious Diseases," [Online]. Available from:‑events/nih‑cli nical‑trial‑investigational‑vaccine‑covid‑19‑begins. [Accessed on 2020 Apr 29].
[58] Moderna Ships mRNA Vaccine Against Novel Coronavirus (mRNA‑1273) for Phase 1 Study," Moderna, Inc. [Online]. Available from: ews‑releases/news‑release‑details/moderna‑ships‑mrna‑vaccine‑against‑novel‑corona virus‑mrna‑1273. [Accessed on 2020 Apr. 29].
[59] N. Chau, "The natural history and transmission potential of asymptomatic SARS- CoV-2 infection," Clin. Infect Dis, 2020.
[60] A. Chau, "Indicate high rates of asymptomatic individuals following SARS- CoV-2 exposure," 2020
[61] Q. Long, "Clinical and immunological assessment of asymptomatic SARS- CoV-2 infections," Nat. Med. 26, pp. 1200–1204, 2020.
[62] J. Zhao, "Antibody responses to SARS- CoV-2 in patients of novel coronavirus disease 2019,' Clin. Infect. Dis, 2020.
[63] L. Ni, "Detection of SARS- CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals," Immunity, 52, pp. 971–977, 2020.
[64] A. Grifoni, "Targets of T cell responses to SARS- CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals," Cell, 181, pp. 1489–1501, 2020.
[65] C. Shen, "Treatment of 5 critically ill patients with COVID-19 with convalescent plasma," JAMA 323, pp. 1582 , 2020.
[66] J. Seow, "Longitudinal evaluation and decline of antibody responses in SARS- CoV-2 infection," Preprint at medRxiv, 2020.
[67] A. Sariol, S. Perlman, "Lessons for COVID-19 immunity from other coronavirus infections," Immunity, 2020.
[68] A. Walls, "Structure, function, and antigenicity of the SARS- CoV-2 spike glycoprotein,' Cell 181, pp. 281–292, 2020.
[69] S. Jiang, C. Hillyer, L. Du, "Neutralizing antibodies against SARS- CoV-2 and other human coronaviruses," Trends Immunol, 41, pp. 355–359, 2020.
[70] J. Duan, "A human SARS- CoV neutralizing antibody against epitope on S2 protein," Biochem. Biophys. Res. Commun, 333, pp. 186–193, 2005.
[71] M. Coughlin, "Generation and characterization of human monoclonal neutralizing antibodies with distinct binding and sequence features against SARS coronavirus using XenoMouse®," Virology 361, pp. 93–102, 2007.
[72] M. Tay, C. Poh, L. Rénia, P. MacAry, L. Ng, "The trinity of COVID-19: immunity, inflammation and intervention," Nat. Rev. Immunol, 20, pp. 363–374, 2020.
[73] P. Arunachalam, "T cell- inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers," Nat. Med, 26, pp. 932–940, 2020.
[74] F. Chunmei, "Dendritic cell and T cell responses, Immunity, 53, pp. 1–14 , 2020.
[75] K. Remy, "Severe immunosuppression and not a cytokine storm characterize COVID-19 infections," JCI Insight, 2020.
[76] M. Liao, "Single- cell landscape of bronchoalveolar immune cells in patients with COVID-19," Nat. Med, 26, pp. 842–844, 2020.