Abstract

Review Article

COVID-19 Vaccines Development: Challenges and Future Perspective

Swapan Kumar Chowdhury, Niranjan Kumar Mridha, Abdul Ashik Khan, Nabajyoti Baildya, Manab Mandal* and Narendra Nath Ghosh*

Published: 09 June, 2025 | Volume 9 - Issue 1 | Pages: 010-020

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) outbursts began at the end of 2019, which imposed a serious crisis on public health and the economy all over the world. To date, there is no antiviral drug available for SARS-CoV-2, and hence vaccination is the most preferred method to prevent people from getting attacked by this virus, especially for those who are at high risk. To counter coronavirus-2, there are various types of vaccines, which are being used, such as live attenuated vaccines, killed or inactivated vaccines, recombinant vaccines, mRNA vaccines, recombinant vector vaccines, and DNA vaccines. Novavax data shows that the vaccine is effective against severe diseases caused by B.1.351. The Pfizer-BioNTech and AstraZeneca vaccines show evidence of some protection against P.1. Due to the immune response, the Human body can recognize and protect itself against harmful foreign substances such as bacteria, viruses, and microorganisms. The immune system protects our body from these harmful substances by identifying them as antigens. Virus-infected cells release many chemicals such as chemokines and cytokines for the initiation of immune response. To control the pandemic situation, herd immunity is required by the immunization of a critical mass of the world population at once. In this review article, we have made an analysis of the immune response of the human body to SARS-CoV-2 infection, different types, and modes of action of SARS-CoV-2 vaccines along with the current status of vaccines.

Read Full Article HTML DOI: 10.29328/journal.ijcv.1001064 Cite this Article Read Full Article PDF

Keywords:

Antigens; Covaxin; COVID-19 vaccine; Variants of mutant COVID-19; Immune response; mRNA vaccines; SARS-CoV-2

References

  1. Chaplin DD. Overview of the immune response. J Allergy Clin Immunol. 2010;125:S3–23. Available from: https://www.jacionline.org/article/S0091-6749(09)02300-7/fulltext
  2. Møller AP, Saino N. Immune response and survival. Oikos. 2004;104:299–304. Available from: https://www.jstor.org/stable/3547960
  3. Parkin J, Cohen B. An overview of the immune system. Lancet. 2001;357:1777–89. Available from: https://www.sciencedirect.com/science/article/pii/S0140673600049047
  4. Medina KL. Overview of the immune system. Handb Clin Neurol. 2016;133:61–76. Available from: https://www.sciencedirect.com/science/article/pii/B9780444634320000049
  5. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. The shape and structure of proteins. In: Molecular Biology of the Cell. 4th ed. New York: Garland Science; 2002. Available from: https://www.ncbi.nlm.nih.gov/books/NBK26830/
  6. Aristizábal B, González Á. Innate immune system. In: Autoimmunity: From Bench to Bedside [Internet]. Bogotá: El Rosario University Press; 2013. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459455/
  7. Aderem A, Ulevitch RJ. Toll-like receptors in the induction of the innate immune response. Nature. 2000;406:782–7. Available from: https://www.nature.com/articles/35021228
  8. Netea MG, Schlitzer A, Placek K, Joosten LA, Schultze JL. Innate and adaptive immune memory: an evolutionary continuum in the host’s response to pathogens. Cell Host Microbe. 2019;25:13–26. Available from: https://www.sciencedirect.com/science/article/pii/S1931312818306273
  9. Roberts K, Alberts B, Johnson A, Walter P, Hunt T. Molecular biology of the cell. New York: Garland Science; 2002.
  10. Stockinger B, Zal T, Zal A, Gray D. B cells solicit their own help from T cells. J Exp Med. 1996;183:891–9. Available from: https://rupress.org/jem/article/183/3/891/47712/B-cells-solicit-their-own-help-from-T-cells
  11. Selders GS, Fetz AE, Radic MZ, Bowlin GL. An overview of the role of neutrophils in innate immunity, inflammation and host-biomaterial integration. Regen Biomater. 2017;4:55–68. Available from: https://academic.oup.com/rb/article/4/1/55/2799181
  12. Elkington P, O'Kane C, Friedland J. The paradox of matrix metalloproteinases in infectious disease. Clin Exp Immunol. 2005;142:12–20. Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2249.2005.02840.x
  13. Mogensen TH. Pathogen recognition and inflammatory signaling in innate immune defenses. Clin Microbiol Rev. 2009;22:240–73. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668232/
  14. Rose NR, Mackay IR. The autoimmune diseases. Amsterdam: Elsevier; 2006. Available from: https://pure.johnshopkins.edu/en/publications/the-autoimmune-diseases-10
  15. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783–801. Available from: https://www.sciencedirect.com/science/article/pii/S0092867406002340
  16. Amarante-Mendes GP, Adjemian S, Branco LM, Zanetti LC, Weinlich R, Bortoluci KR. Pattern recognition receptors and the host cell death molecular machinery. Front Immunol. 2018;9:2379. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2018.02379/full
  17. Jensen S, Thomsen AR. Sensing of RNA viruses: a review of innate immune receptors involved in recognizing RNA virus invasion. J Virol. 2012;86:2900–10. Available from: https://journals.asm.org/doi/10.1128/JVI.05738-11
  18. Schlee M, Hartmann G. Discriminating self from non-self in nucleic acid sensing. Nat Rev Immunol. 2016;16:566–80. Available from: https://www.nature.com/articles/nri.2016.78
  19. Uehata T, Takeuchi O. RNA recognition and immunity—innate immune sensing and its posttranscriptional regulation mechanisms. Cells. 2020;9:1701. Available from: https://www.mdpi.com/2073-4409/9/7/1701
  20. Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2:1–9. Available from: https://www.nature.com/articles/sigtrans201723
  21. Ivashkiv LB, Donlin LT. Regulation of type I interferon responses. Nat Rev Immunol. 2014;14:36–49. Available from: https://www.nature.com/articles/nri3581
  22. Feng H, Zhang YB, Gui JF, Lemon SM, Yamane D. Interferon regulatory factor 1 (IRF1) and anti-pathogen innate immune responses. PLoS Pathog. 2021;17:e1009220. Available from: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009220
  23. Ali S, Mann-Nüttel R, Schulze A, Richter L, Alferink J, Scheu S. Sources of Type I interferons in infectious immunity: plasmacytoid dendritic cells not always in the driver's seat. Front Immunol. 2019;10:778. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2019.00778/full
  24. Platanias LC. Mechanisms of type-I-and type-II-interferon-mediated signalling. Nat Rev Immunol. 2005;5:375–86. Available from: https://www.nature.com/articles/nri1604
  25. De Weerd NA, Nguyen T. The interferons and their receptors—distribution and regulation. Immunol Cell Biol. 2012;90:483–91. Available from: https://www.nature.com/articles/icb20129
  26. Nan Y, Wu C, Zhang YJ. Interplay between Janus kinase/signal transducer and activator of transcription signaling activated by type I interferons and viral antagonism. Front Immunol. 2017;8:1758. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2017.01758/full
  27. Pugnale P, Pazienza V, Guilloux K, Negro F. Hepatitis delta virus inhibits alpha interferon signaling. Hepatology. 2009;49:398–406. Available from: https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.22654
  28. Schneider WM, Chevillotte MD, Rice CM. Interferon-stimulated genes: a complex web of host defenses. Annu Rev Immunol. 2014;32:513–45. Available from: https://www.annualreviews.org/doi/abs/10.1146/annurev-immunol-032713-120231
  29. Crotta S, Davidson S, Mahlakoiv T, Desmet CJ, Buckwalter MR, Albert ML, et al. Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia. PLoS Pathog. 2013;9:e1003773. Available from: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1003773
  30. Rosa BA, Ahmed M, Singh DK, Choreño-Parra JA, Cole J, Jiménez-Álvarez LA, et al. IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection. Commun Biol. 2021;4:1–14. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418717/
  31. Sa Ribero M, Jouvenet N, Dreux M, Nisole S. Interplay between SARS-CoV-2 and the type I interferon response. PLoS Pathog. 2020;16:e1008737. Available from: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008737
  32. Taefehshokr N, Taefehshokr S, Hemmat N, Heit B. Covid-19: Perspectives on innate immune evasion. Front Immunol. 2020;11:580641. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2020.580641/full
  33. Matsumiya T, Stafforini DM. Function and regulation of retinoic acid-inducible gene-I. Crit Rev Immunol. 2010;30(6):489–513. Available from: https://www.ingentaconnect.com/content/ben/cri/2010/00000030/00000006/art00010
  34. Sui L, Zhao Y, Wang W, Wu P, Wang Z, Yu Y, et al. SARS-CoV-2 membrane protein inhibits type I interferon production through ubiquitin-mediated degradation of TBK1. Front Immunol. 2021;12:662989. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2021.662989/full
  35. Seif F, Khoshmirsafa M, Aazami H, Mohsenzadegan M, Sedighi G, Bahar M. The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells. Cell Commun Signal. 2017;15:1–13. Available from: https://biosignaling.biomedcentral.com/articles/10.1186/s12964-017-0177-y
  36. 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;395:497–506. Available from: https://www.sciencedirect.com/science/article/pii/S0140673620301835
  37. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. In: Seminars in immunopathology. Springer; 2017. p. 529–39. Available from: https://link.springer.com/article/10.1007/s00281-017-0629-x
  38. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. T cells and MHC proteins. In: Molecular Biology of the Cell. 4th ed. New York: Garland Science; 2002. Available from: https://www.ncbi.nlm.nih.gov/books/NBK26926/
  39. Vazquez MI, Catalan-Dibene J, Zlotnik A. B cells responses and cytokine production are regulated by their immune microenvironment. Cytokine. 2015;74:318–26. Available from: https://www.sciencedirect.com/science/article/pii/S1043466615000786
  40. Crooke SN, Ovsyannikova IG, Kennedy RB, Poland GA. Immunoinformatic identification of B cell and T cell epitopes in the SARS-CoV-2 proteome. Sci Rep. 2020;10:1–15. Available from: https://www.nature.com/articles/s41598-020-70864-8
  41. Noorimotlagh Z, Karami C, Mirzaee SA, Kaffashian M, Mami S, Azizi M. Immune and bioinformatics identification of T cell and B cell epitopes in the protein structure of SARS-CoV-2: A systematic review. Int Immunopharmacol. 2020;106738. Available from: https://www.sciencedirect.com/science/article/pii/S1567576920302844
  42. Oliveira SC, de Magalhães MT, Homan EJ. Immunoinformatic analysis of SARS-CoV-2 nucleocapsid protein and identification of COVID-19 vaccine targets. Front Immunol. 2020;11:2758. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2020.01220/full
  43. Chang MS, Lu YT, Ho ST, Wu CC, Wei TY, Chen CJ, et al. Antibody detection of SARS-CoV spike and nucleocapsid protein. Biochem Biophys Res Commun. 2004;314:931–6. Available from: https://www.sciencedirect.com/science/article/pii/S0006291X03030464
  44. Chen X, Zhou B, Li M, Liang X, Wang H, Yang G, et al. Serology of severe acute respiratory syndrome: implications for surveillance and outcome. J Infect Dis. 2004;189:1158–63. Available from: https://academic.oup.com/jid/article/189/7/1158/813156
  45. Chen W, Xu Z, Mu J, Yang L, Gan H, Mu F, et al. Antibody response and viraemia during the course of severe acute respiratory syndrome (SARS)-associated coronavirus infection. J Med Microbiol. 2004;53:435–8. Available from: https://www.microbiologyresearch.org/content/journal/jmm/10.1099/jmm.0.45561-0
  46. Wang J, Wen J, Li J, Yin J, Zhu Q, Wang H, et al. Assessment of immunoreactive synthetic peptides from the structural proteins of severe acute respiratory syndrome coronavirus. Clin Chem. 2003;49:1989–96. Available from: https://academic.oup.com/clinchem/article/49/12/1989/5621101
  47. Li G, Chen X, Xu A. Profile of specific antibodies to the SARS-associated coronavirus. N Engl J Med. 2003;349:508–9. Available from: https://www.nejm.org/doi/full/10.1056/NEJM200307313490520
  48. Kirkcaldy RD, King BA, Brooks JT. COVID-19 and postinfection immunity: limited evidence, many remaining questions. JAMA. 2020;323:2245–6. Available from: https://jamanetwork.com/journals/jama/fullarticle/2766097
  49. Fu Y, Pan Y, Li Z, Li Y. The utility of specific antibodies against SARS-CoV-2 in laboratory diagnosis. Front Microbiol. 2020;11:3312. Available from: https://www.frontiersin.org/articles/10.3389/fmicb.2020.603058/full
  50. Li CK, Wu H, Yan H, Ma S, Wang L, Zhang M, et al. T cell responses to whole SARS coronavirus in humans. J Immunol. 2008;181:5490–500. Available from: https://www.jimmunol.org/content/181/8/5490
  51. Shah VK, Firmal P, Alam A, Ganguly D, Chattopadhyay S. Overview of immune response during SARS-CoV-2 infection: lessons from the past. Front Immunol. 2020;11:1949. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2020.01949/full
  52. Seder RA, Ahmed R. Similarities and differences in CD4+ and CD8+ effector and memory T cell generation. Nat Immunol. 2003;4:835–42. Available from: https://www.nature.com/articles/ni969
  53. Kleen TO, Galdon AA, MacDonald AS, Dalgleish AG. Mitigating coronavirus induced dysfunctional immunity for at-risk populations in COVID-19: trained immunity, BCG and “new old friends”. Front Immunol. 2020;11:2059. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2020.02059/full
  54. Buonaguro L, Pulendran B. Immunogenomics and systems biology of vaccines. Immunol Rev. 2011;239:197–208. Available from: https://onlinelibrary.wiley.com/doi/10.1111/j.1600-065X.2010.00971.x
  55. Drexler M. What you need to know about infectious disease. 2014. Available from: https://www.ncbi.nlm.nih.gov/books/NBK209710/
  56. Greenwood B. The contribution of vaccination to global health: past, present and future. Philos Trans R Soc Lond B Biol Sci. 2014;369:20130433. Available from: https://royalsocietypublishing.org/doi/10.1098/rstb.2013.0433
  57. Li G, Gao X, Xiao Y, Liu S, Peng S, Li X, et al. Development of a live attenuated vaccine candidate against duck Tembusu viral disease. Virology. 2014;450:233–42. Available from: https://www.sciencedirect.com/science/article/pii/S0042682213007730
  58. Dai X, Xiong Y, Li N, Jian C. Vaccine types. In: Vaccines - the History and Future. IntechOpen; 2019. Available from: https://www.intechopen.com/chapters/65813
  59. Fenner F, Bachmann PA, Gibbs EPJ, Murphy FA, Studdert MJ, White DO. Cultivation and assay of viruses. Vet Virol. 1987;39. Available from: https://www.sciencedirect.com/science/article/pii/B9780122530555500074
  60. Sanders B, Koldijk M, Schuitemaker H. Inactivated viral vaccines. In: Vaccine analysis: strategies, principles, and control. Springer; 2015. p. 45–80. Available from: https://link.springer.com/chapter/10.1007/978-3-662-45024-6_2
  61. Burrell CJ, Howard CR, Murphy FA. Fenner and White's medical virology. Academic Press; 2016. Available from: https://www.sciencedirect.com/book/9780123751560/fenner-and-whites-medical-virology
  62. Soler E, Houdebine LM. Preparation of recombinant vaccines. Biotechnol Annu Rev. 2007;13:65–94. Available from: https://www.sciencedirect.com/science/article/abs/pii/S1387265607130040
  63. Andersson C. Production and delivery of recombinant subunit vaccines. Bioteknologi. 2000. Available from: https://www.diva-portal.org/smash/get/diva2:8775/FULLTEXT01.pdf
  64. Shouval D. Hepatitis B vaccines. J Hepatol. 2003;39:70–6. Available from: https://www.journal-of-hepatology.eu/article/S0168-8278(03)00152-1/fulltext
  65. Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines—a new era in vaccinology. Nat Rev Drug Discov. 2018;17:261–79. Available from: https://www.nature.com/articles/nrd.2017.243
  66. Xu S, Yang K, Li R, Zhang L. mRNA vaccine era—Mechanisms, drug platform and clinical prospection. Int J Mol Sci. 2020;21:6582. Available from: https://www.mdpi.com/1422-0067/21/18/6582
  67. Reichmuth AM, Oberli MA, Jaklenec A, Langer R, Blankschtein D. mRNA vaccine delivery using lipid nanoparticles. Ther Deliv. 2016;7:319–34. Available from: https://www.future-science.com/doi/10.4155/tde-2016-0006
  68. Aldosari BN, Alfagih IM, Almurshedi AS. Lipid nanoparticles as delivery systems for RNA-based vaccines. Pharmaceutics. 2021;13:206. Available from: https://www.mdpi.com/1999-4923/13/2/206
  69. da Fontoura Budaszewski R, Hudacek A, Sawatsky B, Krämer B, Yin X, Schnell MJ, et al. Inactivated recombinant rabies viruses displaying canine distemper virus glycoproteins induce protective immunity against both pathogens. J Virol. 2017;91:e02077-16. Available from: https://journals.asm.org/doi/full/10.1128/JVI.02077-16
  70. Pollard AJ, Bijker EM. A guide to vaccinology: from basic principles to new developments. Nat Rev Immunol. 2021;21:83–100. Available from: https://www.nature.com/articles/s41577-020-00479-7
  71. Kashte S, Gulbake A, El-Amin SF 3rd, Gupta A. COVID-19 vaccines: rapid development, implications, challenges and future prospects. Hum Cell. 2021;34:711–33. Available from: https://link.springer.com/article/10.1007/s13577-021-00512-4
  72. Liang Z, Zhu H, Wang X, Jing B, Li Z, Xia X, et al. Adjuvants for coronavirus vaccines. Front Immunol. 2020;11:2896. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2020.589833/full
  73. Hotez PJ, Corry DB, Strych U, Bottazzi ME. COVID-19 vaccines: neutralizing antibodies and the alum advantage. Nat Rev Immunol. 2020;20:399–400. Available from: https://www.nature.com/articles/s41577-020-0358-6
  74. Martínez-Flores D, Zepeda-Cervantes J, Cruz-Reséndiz A, Aguirre-Sampieri S, Sampieri A, Vaca L. SARS-CoV-2 vaccines based on the spike glycoprotein and implications of new viral variants. Front Immunol. 2021;12:701501. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2021.701501/full
  75. Coffman RL, Sher A, Seder RA. Vaccine adjuvants: putting innate immunity to work. Immunity. 2010;33:492–503. Available from: https://www.cell.com/immunity/fulltext/S1074-7613(10)00432-5
  76. Kyriakidis NC, López-Cortés A, González EV, Grimaldos AB, Prado EO. SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates. NPJ Vaccines. 2021;6:1–17. Available from: https://www.nature.com/articles/s41541-021-00292-w
  77. Clem AS. Fundamentals of vaccine immunology. J Glob Infect Dis. 2011;3:73. Available from: https://doi.org/10.4103/0974-777x.77299
  78. Jeyanathan M, Afkhami S, Smaill F, Miller MS, Lichty BD, Xing Z. Immunological considerations for COVID-19 vaccine strategies. Nat Rev Immunol. 2020;20:615–32. Available from: https://www.nature.com/articles/s41577-020-00434-6
  79. Kaur SP, Gupta V. COVID-19 Vaccine: A comprehensive status report. Virus Res. 2020;198114. Available from: https://www.sciencedirect.com/science/article/pii/S0168170220304209
  80. Wang N, Shang J, Jiang S, Du L. Subunit vaccines against emerging pathogenic human coronaviruses. Front Microbiol. 2020;11:298. Available from: https://www.frontiersin.org/articles/10.3389/fmicb.2020.00298/full
  81. Duan L, Zheng Q, Zhang H, Niu Y, Lou Y, Wang H. The SARS-CoV-2 spike glycoprotein biosynthesis, structure, function, and antigenicity: Implications for the design of spike-based vaccine immunogens. Front Immunol. 2020;11:2593. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2020.576622/full
  82. Tian JH, Patel N, Haupt R, Zhou H, Weston S, Hammond H, et al. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. Nat Commun. 2021;12:1–14. Available from: https://www.nature.com/articles/s41467-020-20653-8
  83. Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, Ruiz C, Melguizo-Rodríguez L. SARS-CoV-2 infection: The role of cytokines in COVID-19 disease. Cytokine Growth Factor Rev. 2020;54:62–75. Available from: https://www.sciencedirect.com/science/article/pii/S1359610120301036
  84. Mellet J, Pepper MS. A COVID-19 vaccine: big strides come with big challenges. Vaccines. 2021;9:39. Available from: https://www.mdpi.com/2076-393X/9/1/39
  85. Zhang C, Maruggi G, Shan H, Li J. Advances in mRNA vaccines for infectious diseases. Front Immunol. 2019;10:594. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2019.00594/full
  86. Said EA, Tremblay N, Al-Balushi MS, Al-Jabri AA, Lamarre D. Viruses seen by our cells: the role of viral RNA sensors. J Immunol Res. 2018;2018:9480497. Available from: https://www.hindawi.com/journals/jir/2018/9480497/
  87. Dolgin E. CureVac COVID vaccine let-down spotlights mRNA design challenges. Nature. 2021;594:483. Available from: https://www.nature.com/articles/d41586-021-01661-0
  88. Gaviria M, Kilic B. A network analysis of COVID-19 mRNA vaccine patents. Nat Biotechnol. 2021;39:546–8. Available from: https://www.nature.com/articles/s41587-021-00912-9
  89. Firdessa-Fite R, Creusot RJ. Nanoparticles versus dendritic cells as vehicles to deliver mRNA encoding multiple epitopes for immunotherapy. Mol Ther Methods Clin Dev. 2020;16:50–62. Available from: https://www.sciencedirect.com/science/article/pii/S2329050119301446
  90. Hirosue S, Dubrot J. Modes of antigen presentation by lymph node stromal cells and their immunological implications. Front Immunol. 2015;6:446. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2015.00446/full
  91. Luckheeram RV, Zhou R, Verma AD, Xia B. CD4+ T cells: differentiation and functions. Clin Dev Immunol. 2012;2012:925135. Available from: https://www.hindawi.com/journals/cdi/2012/925135/
  92. Crotty S. T follicular helper cell differentiation, function, and roles in disease. Immunity. 2014;41:529–42. Available from: https://www.cell.com/immunity/fulltext/S1074-7613(14)00441-9
  93. Krammer F. SARS-CoV-2 vaccines in development. Nature. 2020;586:516–27. Available from: https://www.nature.com/articles/s41586-020-2798-3
  94. Corum J, Grady D, Wee SL, Zimmer C. Coronavirus vaccine tracker. The New York Times. 2020;5. Available from: https://www.nytimes.com/interactive/2020/science/coronavirus-vaccine-tracker.html
  95. Lauring AS, Hodcroft EB. Genetic variants of SARS-CoV-2—what do they mean? JAMA. 2021;325:529–31. Available from: https://jamanetwork.com/journals/jama/fullarticle/2775006
  96. Khan AA, Dutta T, Mondal MP, Mandal SKC, Ahmed M, Baildya N, et al. Novel Coronavirus Disease (COVID-19): An extensive study on evolution, global health, drug targets and vaccines. Int J Clin Virol. 2021;5:54–69. Available from: https://www.heighpubs.org/jcv/jcv-aid1036.php
  97. Zheng J. SARS-CoV-2: an emerging coronavirus that causes a global threat. Int J Biol Sci. 2020;16:1678. Available from: https://www.ijbs.com/v16p1678.htm
  98. Konings F, Perkins MD, Kuhn JH, Pallen MJ, Alm EJ, Archer BN, et al. SARS-CoV-2 Variants of Interest and Concern naming scheme conducive for global discourse. Nat Microbiol. 2021;6:821–3. Available from: https://www.nature.com/articles/s41564-021-00932-w
  99. Resende PC, Naveca FG, Lins RD, Dezordi FZ, Ferraz MVF, Moreira EG, et al. The ongoing evolution of variants of concern and interest of SARS-CoV-2 in Brazil revealed by convergent indels in the amino (N)-terminal domain of the spike protein. Virus Evol. 2021;7(2):veab069. Available from: https://academic.oup.com/ve/article/7/2/veab069/6330639
  100. Quan PL, Ollé L, Sabaté-Brescó M, Guo Y, Muñoz-Cano R, Wagner A, et al. SARS-CoV-2 vaccine excipients polyethylene glycol and trometamol do not induce mast cell degranulation, in an in vitro model for non-IgE-mediated hypersensitivity. Front Allergy. 2022;3:1046545. Available from: https://www.frontiersin.org/articles/10.3389/falgy.2022.1046545/full
  101. Maurer J, Walles T, Wiese-Rischke C. Optimization of primary human bronchial epithelial 3D cell culture with donor-matched fibroblasts and comparison of two different culture media. Int J Mol Sci. 2023;24(4):4113. Available from: https://www.mdpi.com/1422-0067/24/4/4113
  102. Davidson RM. True or False? At Least 55 Undeclared Chemical Elements Have Been Detected by ICP-MS in COVID-19 “Vaccines”. Int J Vaccine Theory Pract Res. 2024;3(2):1394.1–1394.28.
  103. Davidson RM, Broudy D, Yanowitz S, Santiago D, Oller JW Jr. True or False? At Least 55 Undeclared Chemical Elements Have Been Detected by ICP-MS in COVID-19 “Vaccines”. Int J Vaccine Theory Pract Res. 2024;3(2):1394.1.
  104. Mondal P, Misra D, Chowdhury SK, Mandal V, Dutta T, Baildya N, et al. Exhaled volatile organic compounds (VOCs): A potential biomarkers for chronic disease diagnosis. Volatile Org Compd. 2021;50083. Available from: http://dx.doi.org/10.13140/RG.2.2.10135.50083
  105. Le Gars M, Hendriks J, Sadoff J, Ryser M, Struyf F, Douoguih M, et al. Immunogenicity and efficacy of Ad26.COV2.S: An adenoviral vector–based COVID‐19 vaccine. Immunol Rev. 2022;310(1):47–60. Available from: https://onlinelibrary.wiley.com/doi/10.1111/imr.13088
  106. Sun X, Yang Y, Meng X, Li J, Liu X, Liu H. PANoptosis: Mechanisms, biology, and role in disease. Immunol Rev. 2024;321(1):246–62. Available from: https://onlinelibrary.wiley.com/doi/10.1111/imr.13279
  107. Kircheis R. Coagulopathies after vaccination against SARS-CoV-2 may be derived from a combined effect of SARS-CoV-2 spike protein and adenovirus vector-triggered signaling pathways. Int J Mol Sci. 2021;22(19):10791. Available from: https://www.mdpi.com/1422-0067/22/19/10791
  108. Mandal M, Chowdhury SK, Khan AA, Baildya N, Dutta T, Misra D, et al. Inhibitory efficacy of RNA virus drugs against SARS-CoV-2 proteins: an extensive study. J Mol Struct. 2021;1234:130152. Available from: https://www.sciencedirect.com/science/article/pii/S0022286021004726

Figures:

Figure 1

Figure 1

Figure 1

Figure 2

Figure 1

Figure 3

Figure 1

Figure 4

Figure 1

Figure 5

Figure 1

Figure 6

Similar Articles

Recently Viewed

Read More

Most Viewed

Read More

Help ?