Circulating CTLA-4 Level and CTLA-4 rs733618 Gene Polymorphism Role in Immunological Response to Pfizer BioNTech (BNT162b2) COVID-19 Vaccine in Iraq

Sabah Ezzaldeen, Selda; Sabah Kadhim, Haider; Juad Abdulameer, Atheer

doi:10.30699/ijmm.17.4.474

year 17, Issue 4 (July - August 2023) Iran J Med Microbiol 2023, 17(4): 474-481 | Back to browse issues page

‎ 10.30699/ijmm.17.4.474

Mendeley

Zotero

RefWorks

Sabah Ezzaldeen S, Sabah Kadhim H, Juad Abdulameer A. Circulating CTLA-4 Level and CTLA-4 rs733618 Gene Polymorphism Role in Immunological Response to Pfizer BioNTech (BNT162b2) COVID-19 Vaccine in Iraq. Iran J Med Microbiol 2023; 17 (4) :474-481
URL: http://ijmm.ir/article-1-2213-en.html

Circulating CTLA-4 Level and CTLA-4 rs733618 Gene Polymorphism Role in Immunological Response to Pfizer BioNTech (BNT162b2) COVID-19 Vaccine in Iraq

Selda Sabah Ezzaldeen

¹, Haider Sabah Kadhim²

, Atheer Juad Abdulameer³

1- Department of Microbiology, College of Medicine, Al-Nahrain University, Baghdad, Iraq , seldaezzaldeen@gmail.com
2- Department of Microbiology, College of Medicine, Al-Nahrain University, Baghdad, Iraq
3- Department of Family and Community Medicine, College of Medicine, Al-Nahrain University, Baghdad, Iraq

Abstract: (778 Views)

Background and Aim: Immune response to BNT162b2 COVID-19 vaccine among people is not the same. Genetic polymorphism in inhibitory immune checkpoints may have an important role in immune response after vaccination; therefore, we aimed to demonstrate the role of CTLA-4 rs733618 gene polymorphism and the amount of circulating CTLA-4 in individuals vaccinated with the BNT162b2 vaccine following the booster dose.
Materials and Methods: This research is a cross-sectional study performed on 180 healthy adults (above 18 years old) vaccinated with the BNT162b2 COVID-19 vaccine 21-30 days after the second dose at the community dwelling from December 2021 to April 2022. After DNA extraction from the sample’s blood, Allele-specific polymerase chain reaction (ASPCR) was developed to detect single nucleotide polymorphisms of CTLA-4 rs733618. The levels of IgG in the serum, which are directed towards the spike protein-1 and soluble CTLA-4, were quantified using an Enzyme-linked Immunosorbent Assay (ELISA).
Results: The current study showed no significant association in CTLA-4 rs733618 genotype distribution and immune response to the BNT162b2 vaccine, Furthermore, there was a highly significant difference between CTLA-4 serum levels and CTLA-4 rs733618 genotype frequency.
Conclusion: CTLA-4 -1722 T/C rs733618 is not significantly related to immunological response to the BNT162b2 vaccine. The level of s-CTLA-4 production may be affected by CTLA-4rs733618 polymorphism. rs733618 (T/C) and rs733618(C/C) genotypes significantly related with high level of s-CTLA-4, while rs733618 T/T genotype related with low level of s-CTLA-4.

Keywords: Anti-S1 IgG response, BNT162b2, CTLA-4 Gene Polymorphism, mRNA Vaccine, rs733618

Full-Text [PDF 530 kb] (310 Downloads) | | Full-Text (HTML) (118 Views)

Type of Study: Original Research Article | Subject: Microbial Immunology
Received: 2023/05/3 | Accepted: 2023/09/19 | ePublished: 2023/09/27

References

1. Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges. Int J Antimicrob Agents. 2020; 55(3):105924. [DOI:10.1016/j.ijantimicag.2020.105924] [PMID] [PMCID]

2. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet. 2020;395(10224):565-74. [DOI:10.1016/S0140-6736(20)30251-8] [PMID]

3. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet. 2020;395(10223):507-13. [DOI:10.1016/S0140-6736(20)30211-7] [PMID]

4. Vasei M, Jafari E, Falah Azad V, Safavi M, Sotoudeh M. Molecular Diagnosis of COVID-19; Biosafety and Pre-analytical Recommendations. Iran J Pathol. 2023;18(3):244-56. [DOI:10.30699/ijp.2023.1988405.3061]

5. Hassan SA, Sheikh FN, Jamal S, Ezeh JK, Akhtar A. Coronavirus (COVID-19): a review of clinical features, diagnosis, and treatment. Cureus. 2020; 12(3):e7355. [DOI:10.7759/cureus.7355]

6. Khorasani Esmaili P, Dabiri S, Movahedinia S, Shojaeepour S, Bagheri F, Ranjbar H, et al. Evaluation of Laboratory Findings of Patients with Coronavirus Disease 2019 in Kerman, Iran. Iran J Pathol, 2023;18(3):347-55. [DOI:10.30699/ijp.2023.1971332.3031]

7. Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Di Napoli R. Features, evaluation and treatment coronavirus (COVID-19). Statpearls [internet]: StatPearls Publishing; 2020.

8. Wang HY, Li XL, Yan ZR, Sun XP, Han J, Zhang BW. Potential neurological symptoms of COVID-19. Therap Adv Neurol Disorder. 2020;13: 1756286420917830. [DOI:10.1177/1756286420917830] [PMID] [PMCID]

9. Rezabeigi-Davarani E, Bokaie S, Mashayekhi V, Sharifi L, Faryabi R, Alian Samakkhah S, et al. Epidemiological and clinical characteristics of COVID-19 patients studied by Jiroft University of Medical Sciences: Southeast of Iran. J Adv Med Biomed Res. 2021;29(136):302-9. [DOI:10.30699/jambs.29.136.302]

10. Mahmoodpoor A, Hosseini M, Soltani-Zangbar S, Sanaie S, Aghebati-Maleki L, Saghaleini SH, et a. Reduction and exhausted features of T lymphocytes under serological changes, and prognostic factors in COVID-19 progression. Mol Immunol. 2021;138:121-7. [DOI:10.1016/j.molimm.2021.06.001] [PMID] [PMCID]

11. Aghbash PS, Eslami N, Shamekh A, Entezari-Maleki T, Baghi HB. SARS-CoV-2 infection: The role of PD-1/PD-L1 and CTLA-4 axis. Life Sci. 2021; 270:119124. [DOI:10.1016/j.lfs.2021.119124] [PMID] [PMCID]

12. Garg K, Talwar D, Mahajan SN, Karim S, Prajapati K, Patel S, et al. A review on COVID-19 vaccinations. Biomed Biotechnol Res J. 2022;6(1): 50-3. [DOI:10.4103/bbrj.bbrj_280_21]

13. Simões RS, Rodríguez-Lázaro D. Classical and next-generation vaccine platforms to SARS-CoV-2: biotechnological strategies and genomic variants. Int J Environ Res Public Health. 2022; 19(4):2392. [DOI:10.3390/ijerph19042392] [PMID] [PMCID]

14. Majed SO. Comparison of Antibody Levels Produced by Pfizer, AstraZeneca, and Sinopharm Vaccination in COVID-19 Patients in Erbil City-Iraq. Cell Mol Biol. 2023;69(3):103-12. [DOI:10.14715/cmb/2023.69.3.14] [PMID]

15. Kollewe J. From Pfizer to Moderna: who's making billions from Covid-19 vaccines. The Guardian. 2021;6.

16. Dolgin E. The tangled history of mRNA vaccines. Nature. 2021;597(7876):318-24. [DOI:10.1038/d41586-021-02483-w] [PMID]

17. Verbeke R, Lentacker I, De Smedt SC, Dewitte H. The dawn of mRNA vaccines: The COVID-19 case. J Control Release. 2021;333:511-20. [DOI:10.1016/j.jconrel.2021.03.043] [PMID] [PMCID]

18. Zeng C, Zhang C, Walker PG, Dong Y. Formulation and delivery technologies for mRNA vaccines. InmRNA Vaccines. 2020. (pp. 71-110). Cham: Springer International Publishing. [DOI:10.1007/82_2020_217] [PMID] [PMCID]

19. Wadhwa A, Aljabbari A, Lokras A, Foged C, Thakur A. Opportunities and challenges in the delivery of mRNA-based vaccines. Pharmaceutics. 2020; 12(2):102. [DOI:10.3390/pharmaceutics12020102] [PMID] [PMCID]

20. Hassan RT, Mohammed SH. Evaluation of immunoglobulin G level among subjects vaccinated with different types of COVID-19 vaccines in the karbala population, Iraq. Biomed Biotechnol Res J. 2022;6(3):466-471. [DOI:10.4103/bbrj.bbrj_213_22]

21. Sannathimmappa MB, Nambiar V, Aravindakshan R, Baig MF, Hassan AK, Al-Balushi MS. Effectiveness and adverse effects of astrazeneca and pfizer COVID-19 vaccines among medical students in Oman: A comparative study. Biomed Biotechnol Res J. 2023;7(1):101-5. [DOI:10.4103/bbrj.bbrj_9_23]

22. Kiani J, Khadempar S, Hajilooi M, Rezaei H, Keshavarzi F, Solgi G. Cytotoxic T lymphocyte antigen-4 gene variants in type 2 diabetic patients with or without neuropathy. Iran J Allergy Asthma Immunol. 2016;220-8.

23. Batista-Duharte A, Hassouneh F, Alvarez-Heredia P, Pera A, Solana R. Immune checkpoint inhibitors for vaccine improvements: Current status and new approaches. Pharmaceutics. 2022;14(8):1721. [DOI:10.3390/pharmaceutics14081721] [PMID] [PMCID]

24. Kang CK, Kim HR, Song KH, Keam B, Choi SJ, Choe PG, et al. Cell-mediated immunogenicity of influenza vaccination in patients with cancer receiving immune checkpoint inhibitors. J Infect Dis. 2020;222(11):1902-9. [DOI:10.1093/infdis/jiaa291] [PMID]

25. Leng Q, Bentwich Z, Borkow G. CTLA-4 upregulation during aging. Mech. Ageing Dev. 2002;123(10):1419-21. [DOI:10.1016/S0047-6374(02)00077-5] [PMID]

26. Chen Y, Wang Q, Shi B, Xu P, Hu Z, Bai L, et al. Development of a sandwich ELISA for evaluating soluble PD-L1 (CD274) in human sera of different ages as well as supernatants of PD-L1+ cell lines. Cytokine. 2011;56(2):231-8. [DOI:10.1016/j.cyto.2011.06.004] [PMID]

27. Thio CL, Mosbruger TL, Kaslow RA, Karp CL, Strathdee SA, Vlahov D, et al. Cytotoxic T-lymphocyte antigen 4 gene and recovery from hepatitis B virus infection. J Virol. 2004;78(20):11258-62. [DOI:10.1128/JVI.78.20.11258-11262.2004] [PMID] [PMCID]

28. Hudson L, Rocca K, Song W and Pandey P. CTLA-4 gene polymorphisms in systemic lupus erythematosus, ahighly significant association with a determinant in the promoter region. Hum Genet. 2002;111:452-5. [DOI:10.1007/s00439-002-0807-2] [PMID]

29. Talib AL, Kadhim HS, Muhammed AK. Evaluation of Cytotoxic T-Lymphocyte Antigen 4 Polymorphism and Soluble Immune Checkpoint Level Among A Sample of Sars-Cov-2 Iraqi Patients. Pakistan J Medical Health Sci. 2022;16(4):417-9. [DOI:10.53350/pjmhs22164417]

30. Mahdi YS, Kadhim HS. Evaluation of cytotoxic T-lymphocyte Antigen-4 (+49A/G) gene polymorphism in chronic hepatitis B virus infection. Iraqi J Med Sci. 2020;18(2):101-9. [DOI:10.22578/IJMS.18.2.3]

31. Simone R, Pesce G, Antola P, Rumbullaku M, Bagnasco M, Bizzaro N, et al. The soluble form of CTLA-4 from serum of patients with autoimmune diseases regulates T-cell responses. Biomed Res Int. 2014;2014:215763. [DOI:10.1155/2014/215763] [PMID] [PMCID]

32. Beserra DR, Alberca RW, Branco AC, Oliveira LM, de Souza Andrade MM, Gozzi-Silva SC, et al. Upregulation of PD-1 expression and high sPD-L1 levels associated with COVID-19 severity. J Immunol Res. 2022;2022:9764002. [DOI:10.1155/2022/9764002] [PMID] [PMCID]