Improvement of the inactivated SARS-CoV-2 vaccine potency through formulation in alum/naloxone adjuvant; Robust T cell and anti-RBD IgG responses | ||
Iranian Journal of Basic Medical Sciences | ||
مقاله 2، دوره 25، شماره 5، مرداد 2022، صفحه 554-561 اصل مقاله (738.21 K) | ||
نوع مقاله: Original Article | ||
شناسه دیجیتال (DOI): 10.22038/ijbms.2022.63527.14015 | ||
نویسندگان | ||
Melika Haghighi1، 2؛ Akbar Khorasani3؛ Pegah Karimi1، 2؛ Mehdi Mahdavi* 1، 2، 4 | ||
1Advanced Therapy Medicinal Product (ATMP) Department, Breast Cancer Research Center, Motamed Cancer Institute, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran | ||
2Recombinant Vaccine Research Center, Tehran University of Medical Sciences, Tehran, Iran | ||
3Department of FMD Vaccine Production, Razi Vaccine & Serum Research Institute, Agricultural Research, Education & Extension Organization (AREEO), Karaj, Iran | ||
4Immunotherapy Group, The Institute of Pharmaceutical Science (TIPS), Tehran University of Medical Science, Tehran, Iran | ||
چکیده | ||
Objective(s): SARS-CoV-2, emerging as a major threat to public health, has to be controlled through vaccination. Naloxone (NLX), an opioid receptor antagonist, demonstrated its adjuvant activity for microbial vaccines. In this study, inactivated SARS-CoV-2 was developed in the Alum/NLX adjuvant to increase the potency of the inactivated SARS-CoV-2 vaccine. Materials and Methods: BALB/c mice were immunized on days 0 and 14 with inactivated SARS-CoV-2-Alum, -Alum + NLX 3 mg/kg, -Alum + NLX 10 mg/kg, and -Freund adjuvant, as well as PBS. IFN-γ and IL-4 cytokines and Granzyme-B release were assessed with ELISA. In addition, specific total IgG, IgG1/IgG2a isotypes, and ratio as well as anti-RBD IgG responses were assessed with an optimized ELISA. Results: SARS-CoV-2-Alum-NLX10 group showed a significant increase in the IFN-γ cytokine response versus SARS-CoV-2-Alum, SARS-CoV-2-Alum-NLX3, and PBS groups. The SARS-CoV-2-Alum-NLX3 group exhibited a significant decrease in IL-4 cytokine versus SARS-CoV-2-Alum. The mice immunized with SARS-CoV-2-Alum-NLX10 showed a significant increase in CTL activity versus SARS-CoV-2-Alum and PBS. In addition, mice immunized with SARS-CoV-2-Alum-NLX3, SARS-CoV-2-Alum-NLX10 and SARS-CoV-2-Freund demonstrated an increase in IgG response, as compared with SARS-CoV-2-Alum and PBS group. Furthermore, all formulations of SARS-CoV-2 vaccines could induce both IgG1 and IgG2a isotypes. But, the IgG2a/IgG1 ratio in SARS-CoV-2-Freund and SARS-CoV-2-Alum-NLX10 revealed an increase as compared with that of the SARS-CoV-2-Alum group. Anti-RBD IgG response in the SARS-CoV-2-Alum-NLX10 group showed a significant increase as compared with the Alum-based vaccine. Conclusion: Formulation of inactivated SARS-CoV-2 virus in NLX/alum adjuvant improved the potency of humoral and, especially, cellular responses. | ||
کلیدواژهها | ||
Alum Adjuvant؛ Immune responses؛ Inactivated SARS-CoV-2 - virus؛ Naloxone؛ Vaccine formulation | ||
مراجع | ||
1. Shi Y, Wang G, Cai XP, Deng JW, Zheng L, Zhu HH, et al. An overview of COVID-19. J Zhejiang Univ Sci B 2020;21:343-360. 2. Chang L, Yan Y, Wang L. Coronavirus disease 2019: Coronaviruses and blood safety. Transfus Med Rev 2020;34:75-80. 3. The Lancet Infectious D. Challenges of coronavirus disease 2019. Lancet Infect Dis 2020;20:261. 4. Dhama K, Khan S, Tiwari R, Sircar S, Bhat S, Malik YS, et al. Coronavirus disease 2019-COVID-19. Clin Microbiol Rev 2020;33:1-48. 5. Alkandari D, Herbert JA, Alkhalaf MA, Yates C, Panagiotou S. SARS-CoV-2 vaccines: Fast track versus efficacy. Lancet Microbe 2021;2:e89-e90. 6. Iqbal Yatoo M, Hamid Z, Parray OR, Wani AH, Ul Haq A, Saxena A, et al. COVID-19-recent advancements in identifying novel vaccine candidates and current status of upcoming SARS-CoV-2 vaccines. Hum Vaccin Immunother 2020;16:2891-2904. 7. Dhama K, Sharun K, Tiwari R, Dadar M, Malik YS, Singh KP, et al. COVID-19, an emerging coronavirus infection: Advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics. Human vaccines & immunotherapeutics. 2020;16:1232-1238. 8. Jafari A, Danesh Pouya F, Niknam Z, Abdollahpour-Alitappeh M, Rezaei-Tavirani M, Rasmi Y. Current advances and challenges in COVID-19 vaccine development: from conventional vaccines to next-generation vaccine platforms. Mol Biol Rep 2022;Vol:1-15. 9. Najminejad H, Kalantar SM, Mokarram AR, Dabaghian M, Abdollahpour-Alitappeh M, Ebrahimi SM, et al. Bordetella pertussis antigens encapsulated into N-trimethyl chitosan nanoparticulate systems as a novel intranasal pertussis vaccine. Artif Cells Nanomed Biotechnol 2019;47:2605-2611. 10. Amini Y, Tebianian M, Mosavari N, Fasihi Ramandi M, Ebrahimi SM, Najminejad H, et al. Development of an effective delivery system for intranasal immunization against Mycobacterium tuberculosis ESAT-6 antigen. Artif Cells Nanomed Biotechnol 2017;45:291-296. 11. Corey L, Mascola JR, Fauci AS, Collins FS. A strategic approach to COVID-19 vaccine R&D. Science 2020;368:948-950. 12. Mahdavi M, Ebtekar M, Khorshid HRK, Azadmanesh K, Hartoonian C, Hassan ZM. ELISPOT analysis of a new CTL based DNA vaccine for HIV-1 using GM-CSF in DNA prime/peptide boost strategy: GM-CSF induced long-lived memory responses. Immunology letters 2011;140:14-20. 13. Wang J, Peng Y, Xu H, Cui Z, Williams RO. The COVID-19 vaccine race: challenges and opportunities in vaccine formulation. AAPS PharmSciTech 2020;21:1-12. 14. Kuo T-Y, Lin M-Y, Coffman RL, Campbell JD, Traquina P, Lin Y-J, et al. Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19. Scientific Reports 2020;10:1-10. 15. García-Arriaza J, Garaigorta U, Pérez P, Lázaro-Frías A, Zamora C, Gastaminza P, et al. COVID-19 vaccine candidates based on modified vaccinia virus ankara expressing the SARS-CoV-2 spike protein induce robust t-and b-cell immune responses and full efficacy in mice. J Virol 2021;95:e02260-20. 16. Cox RJ, Brokstad KA. Not just antibodies: B cells and T cells mediate immunity to COVID-19. Nat Rev Immunol 2020;20:581-582. 17. Beyer WEP, Palache AM, Reperant LA, Boulfich M, Osterhaus A. Association between vaccine adjuvant effect and pre-seasonal immunity. Systematic review and meta-analysis of randomised immunogenicity trials comparing squalene-adjuvanted and aqueous inactivated influenza vaccines. Vaccine. 2020;38:1614-1622. 18. Jamali A, Mahdavi M, Hassan ZM, Sabahi F, Farsani MJ, Bamdad T, et al. A novel adjuvant, the general opioid antagonist naloxone, elicits a robust cellular immune response for a DNA vaccine. Int Immunol 2009;21:217-225. 19. Burris S, Norland J, Edlin BR. Legal aspects of providing naloxone to heroin users in the United States. International Journal of Drug Policy 2001;12:237-248. 20. Yasaghi M, Mahdavi M. Potentiation of human papilloma vaccine candidate using naloxone/alum mixture as an adjuvant: increasing immunogenicity of HPV-16E7d vaccine. Iran J Basic Med Sci 2016; 19: 1003–1009. 21. Jamali A, Mahdavi M, Shahabi S, Hassan ZM, Sabahi F, Javan M, et al. Naloxone, an opioid receptor antagonist, enhances induction of protective immunity against HSV-1 infection in BALB/c mice. Microb Pathog 2007;43:217-223. 22. Jazani NH, Karimzad M, Mazloomi E, Sohrabpour M, Hassan ZM, Ghasemnejad H, et al. Evaluation of the adjuvant activity of naloxone, an opioid receptor antagonist, in combination with heat-killed Listeria monocytogenes vaccine. Microbes Infect 2010;12:382-388. 23. Velashjerdi Farahani S, Reza Aghasadeghi M, Memarnejadian A, Faezi S, Shahosseini Z, Mahdavi M, et al. Naloxone/alum mixture a potent adjuvant for HIV-1 vaccine: induction of cellular and poly-isotypic humoral immune responses. Pathog Glob Health 2016;110:39-47. 24. Kaffashi A, Huang J, Bairami A, Fallah Mehrabadi MH, Yaslianifard S, Bashashati M, et al. Complete genome sequencing and molecular characterization of SARS-COV-2 from COVID-19 cases in Alborz province in Iran. Heliyon 2021;7:e08027. 25. Fathi M, Nezamzadeh R, Abdollahpour‐Alitappeh M, Yazdi MH, Khoramabadi N, Mahdavi M. Formulation of a recombinant HIV‐1 polytope candidate vaccine with naloxone/alum mixture: Induction of multi‐cytokine responses with a higher regulatory mechanism. APMIS 2021;129:480-488. 26. Mojarab S, Shahbazzadeh D, Moghbeli M, Eshraghi Y, Bagheri KP, Rahimi R, et al. Immune responses to HIV-1 polytope vaccine candidate formulated in aqueous and alcoholic extracts of Propolis: Comparable immune responses to Alum and Freund adjuvants. Microbial Pathogenesis 2020;140:103932. 27. Mahdavi M, Tajik AH, Ebtekar M, Rahimi R, Adibzadeh MM, Moozarmpour HR, et al. Granulocyte‐macrophage colony‐stimulating factor, a potent adjuvant for polarization to Th‐17 pattern: an experience on HIV‐1 vaccine model. Apmis. 2017;125:596-603. 28. Pi-Estopiñan F, Pérez MT, Fraga A, Bergado G, Díaz GD, Orosa I, et al. A cell-based ELISA as surrogate of virus neutralization assay for RBD SARS-CoV-2 specific antibodies. Vaccine 2022;40:1958-1967. 29. Hellewell J, Abbott S, Gimma A, Bosse NI, Jarvis CI, Russell TW, et al. Feasibility of controlling COVID-19 outbreaks by isolation of cases and contacts. Lancet Global Health 2020;8:e488-e96. 30. Forni G, Mantovani A. Covid-19 vaccines: Where we stand and challenges ahead. Cell Death Differ 2021;28:626-639. 31. Liu X, Liu C, Liu G, Luo W, Xia N. Covid-19: Progress in diagnostics, therapy and vaccination. Theranostics 2020;10:7821-7835. 32. Lazarus JV, Ratzan SC, Palayew A, Gostin LO, Larson HJ, Rabin K, et al. A global survey of potential acceptance of a Covid-19 vaccine. Nat Med 2021;27:225-228. 33. Kim JH, Marks F, Clemens JD. Looking beyond Covid-19 vaccine phase 3 trials. Nat Med 2021;27:205-211. 34. Jazani NH, Parsania S, Sohrabpour M, Mazloomi E, Karimzad M, Shahabi S. Naloxone and alum synergistically augment adjuvant activities of each other in a mouse vaccine model of Salmonella typhimurium infection. Immunobiology 2011;216:744-751. 35. Khorshidvand Z, Shahabi S, Mohamadzade H, Daryani A, Tappeh KH. Mixture of alum–naloxone and alum–naltrexone as a novel adjuvant elicits immune responses for Toxoplasma gondii lysate antigen in BALB/c mice. Experimental Parasitology 2016;162:28-34. 36. Sacerdote P, Gaspani L, Panerai AE. The opioid antagonist naloxone induces a shift from type 2 to type 1 cytokine pattern in normal and skin‐grafted mice. Ann N Y Acad Sci 2000;917:755-763. 37. Hassan ATM, Hassan ZM, Moazzeni SM, Mostafaie A, Shahabi S, Ebtekar M, et al. Naloxone can improve the anti-tumor immunity by reducing the CD4+ CD25+ Foxp3+ regulatory T cells in BALB/c mice. Int Immunopharmacol 2009;9:1381-1386. 38. Rostami H, Ebtekar M, Ardestani MS, Yazdi MH, Mahdavi M. Co-utilization of a TLR5 agonist and nano-formulation of HIV-1 vaccine candidate leads to increased vaccine immunogenicity and decreased immunogenic dose: A preliminary study. Immunol Lett 2017;187:19-26. 39. Jazani NH, Sohrabpour M, Mazloomi E, Shahabi SJFI, Microbiology M. A novel adjuvant, a mixture of alum and the general opioid antagonist naloxone, elicits both humoral and cellular immune responses for heat-killed Salmonella typhimurium vaccine. FEMS Immunol Med Microbiol 2011;61:54-62. 40. Caielli S, Veiga DT, Balasubramanian P, Athale S, Domic B, Murat E, et al. A CD4+ T cell population expanded in lupus blood provides B cell help through interleukin-10 and succinate. Nat Med 2019;25:75-81. 41. Kim ST, Choi J-Y, Lainez B, Schulz VP, Karas DE, Baum ED, et al. Human extrafollicular CD4+ Th cells help memory B cells produce Igs. J Immunol 2018;201:1359-1372. 42. Jazani NH, Parsania S, Sohrabpour M, Mazloomi E, Karimzad M, Shahabi SJI. Naloxone and alum synergistically augment adjuvant activities of each other in a mouse vaccine model of Salmonella typhimurium infection. Immunobiology 2011;216:744-751. 43. Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med 2021;27:1205-1211. 44. Starr TN, Czudnochowski N, Liu Z, Zatta F, Park YJ, Addetia A, et al. SARS-CoV-2 RBD antibodies that maximize breadth and resistance to escape. Nature 2021 Sep;597:97-102. 45. Sauer K, Harris T. An Effective COVID-19 Vaccine Needs to Engage T Cells. Front Immunol 2020;11:581807. 46. Cañete PF, Vinuesa CG. COVID-19 makes B cells forget, but T cells remember. Cell 2020;183:13-15. | ||
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