Level of IgG antibodies, tumor necrosis factor alpha and T-cell exhaustion in persons vaccinated against SARS-CoV-2

Authors

  • Ivan Lozada Requena Universidad Peruana Cayetano Heredia.Laboratorios de Investigación y Desarrollo. Facultad de Ciencias e Ingeniería. Lima, Perú https://orcid.org/0000-0002-3615-8964
  • Diego Paredes Inofuente Universidad Peruana Cayetano Heredia.Laboratorios de Investigación y Desarrollo. Facultad de Ciencias e Ingeniería. Lima, Perú https://orcid.org/0000-0002-9680-1210

DOI:

https://doi.org/10.20453/rmh.v35i3.5258

Keywords:

Antibodies, cytokines, COVID-19, immunoglobulin G, SARS-CoV-2, T-Lymphocytes

Abstract

Immunity against COVID-19 is crucial. Little is known about the mechanisms involved in stimulating antibody production against SARS-CoV-2 by the tumor necrosis factor alpha (TNF-α) and the exhaustion of T-cells. Objective: To evaluate the IgG (anti-spike) response, TNF-α, T-cell subsets, and their exhaustion. Methods: Serum samples and peripheral mononuclear cells of subjects with infection (G1, n=07), asymptomatic (G2, n=08 y G3, n=10) vaccinated with three doses of the BNT162b2 (G1 and G2) or the ChAdOx1-S (G3) vaccines. ELISA determined the level of IgG and TNF-α, and flow cytometry determined the T-cell subsets and exhaustion. Results: No change was observed in the levels of IgG before and after vaccination. G1 significantly increased TNF-α levels after receiving the third vaccine dose. Total lymphocytes significantly decreased in G2, but CD3+ did not change. G3 had a reduction in LTCD4+ and an increase in PD-1+, LTCD8+, and PD-1+ before and after the third vaccine dose. A positive correlation was observed after the third vaccine dose in G3 among IgG and CD4+PD-1+(p=0.034) and CD8+PD-1+(p=0.028), respectively. Conclusions: Humoral (IgG) and inflammatory (TNF-α) responses were not modified significantly; the heterologous vaccine (G3) increased levels of CD4+ cells, a subset that sustains antiviral adaptative immunity, and avoids T-cell exhaustion.

Downloads

Download data is not yet available.

Author Biographies

Ivan Lozada Requena, Universidad Peruana Cayetano Heredia.Laboratorios de Investigación y Desarrollo. Facultad de Ciencias e Ingeniería. Lima, Perú

         

Diego Paredes Inofuente, Universidad Peruana Cayetano Heredia.Laboratorios de Investigación y Desarrollo. Facultad de Ciencias e Ingeniería. Lima, Perú

Bachiller en Ciencias Biológicas de UPCH

References

He F, Deng Y, Li W. Coronavirus disease 2019: What we know? J Med Virol. 2020 Jul 1;92(7):719–25.

Agencia EFE. Segunda ola lleva a Perú a rebasar los 100,000 fallecidos en pandemia respecto a años anteriores | PERU | GESTIÓN. [citado el 20 de junio de 2023]; Disponible en: https://gestion.pe/peru/segunda-ola-lleva-a-peru-a-rebasar-los-100000-fallecidos-en-pandemia-respecto-a-anos-anteriores-noticia/

Ministerio de Salud. Minsa declara el fin de la quinta ola de la COVID-19 en el país – CDC MINSA [Internet]. [citado el 20 de junio de 2023]. Disponible en: https://www.dge.gob.pe/portalnuevo/informativo/prensa/minsa-declara-el-fin-de-la-quinta-ola-de-la-covid-19-en-el-pais/

Ministerio de Salud. Minsa descarta una sexta ola de covid-19 en el país - Noticias - Ministerio de Salud - Plataforma del Estado Peruano [Internet]. [citado el 20 de junio de 2023]. Disponible en: https://www.gob.pe/institucion/minsa/noticias/741412-minsa-descarta-una-sexta-ola-de-covid-19-en-el-pais/

Ragab D, Salah Eldin H, Taeimah M, Khattab R, Salem R. The COVID-19 Cytokine Storm; What We Know So Far. Frontiers in Immunology | www.frontiersin.org [Internet]. 2020 [citado el 17 de junio de 2023];1:1446. Disponible en: www.frontiersin.org

Jose RJ, Manuel A. COVID-19 cytokine storm: the interplay between inflammation and coagulation. Lancet Respir Med. 2020; 8(6):e46–7. doi: 10.1016/S2213-2600(20)30216-2. Epub 2020 Apr 27.

Fara A, Mitrev Z, Rosalia RA, Assas BM. Cytokine storm and COVID-19: a chronicle of pro-inflammatory cytokines: Cytokine storm: The elements of rage! Open Biol. 2020;10(9) :200160. doi: 10.1098/rsob.200160. Epub 2020 Sep 23.

Sarzi-Puttini P, Giorgi V, Sirotti S, Marotto D, Ardizzone S, Rizzardini G, et al. COVID-19, cytokines and immunosuppression: what can we learn from severe acute respiratory syndrome? Clin Exp Rheumatol. 2020;38(2):337–42. doi: 10.55563/clinexprheumatol/xcdary. Epub 2020 Mar 22.

Gupta S, Bi R, Kim C, Chiplunkar S, Yel L, Gollapudi S. Role of NF-kB signaling pathway in increased tumor necrosis factor-α-induced apoptosis of lymphocytes in aged humans. Cell Death Differ [Internet]. 2005 [citado el 18 de junio de 2023];12:177–83. Disponible en: www.nature.com/cdd

Chen DP, Wen YH, Lin WT, Hsu FP. Association between the side effect induced by COVID-19 vaccines and the immune regulatory gene polymorphism. Front Immunol. 2022 Oct 26;13: 941497. doi: 10.3389/fimmu.2022.941497.

Abbas A, Lichtman A, Pillai S. Cellular and Molecular Immunology. 10Th ed. Philadelphia: Elsevier. 2021.

Jordan SC. Innate and adaptive immune responses to SARS-CoV-2 in humans: relevance to acquired immunity and vaccine responses. 2021 Jun; 204(3):310-320. doi: 10.1111/cei.13582. Epub 2021 Mar 4.

Long QX, Liu BZ, Deng HJ, Wu GC, Deng K, Chen YK. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. Jun;26(6):845-848. doi: 10.1038/s41591-020-0897-1

Diao B, Wang C, Tan Y, Chen X, Liu Y, Ning L, et al. Reduction and Functional Exhaustion of T Cells in Patients with Coronavirus Disease 2019 (COVID-19). Front Immunol. 2020 May 1; 11:827. doi: 10.3389/fimmu.2020.00827.

Morris G, Bortolasci CC, Puri BK, Olive L, Marx W, O’neil A, et al. The pathophysiology of SARS-CoV-2: A suggested model and therapeutic approach. Life Sci. 2020 Oct 1; 258:118166. doi: 10.1016/j.lfs.2020.118166. Epub 2020 Jul 31.

Kaneko N, Kuo HH, Boucau J, Farmer JR, Allard-Chamard H, Mahajan VS, et al. Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19. Cell. 2020;183(1):143-157.e13.

Rha MS, Shin EC. Activation or exhaustion of CD8 + T cells in patients with COVID-19. Cell Mol Immunol. 2021;18. Doi: 10.1038/s41423-021-00750-4

Alahdal M, Elkord E. Exhaustion and over-activation of immune cells in COVID-19: Challenges and therapeutic opportunities. Clin Immunol. 2022; 245:109177. Doi:10.1016/j.clim.2022.109177.

Shahbaz S, Xu L, Sligl W, Osman M, Bozorgmehr N, Mashhouri S, et al. The Quality of SARS-CoV-2–Specific T Cell Functions Differs in Patients with Mild/Moderate versus Severe Disease, and T Cells Expressing Coinhibitory Receptors Are Highly Activated. J. Immun. 2021 Aug 15;207(4):1099–111. Doi: 10.4049/jimmunol.2100446

Gurshaney S, Morales-Alvarez A, Ezhakunnel K, Manalo A, Huynh TH, Abe JI, et al. Metabolic dysregulation impairs lymphocyte function during severe SARS-CoV-2 infection. Commun Biol. 2023 Dec 1; 6(374). Doi: 10.1038/s42003-023-04730-4.

Li M, Guo W, Dong Y, Wang X, Dai D, Liu X, et al. Elevated Exhaustion Levels of NK and CD8+ T Cells as Indicators for Progression and Prognosis of COVID-19 Disease. Front. Immunol. 11:580237. doi: 10.3389/fimmu.2020.580237.

Haanen JB, Cerundolo V. NKG2A, a New Kid on the Immune Checkpoint Block. Cell. 2018 Dec 13;175(7):1720-1722. Doi: 10.1016/j.cell.2018.11.048.

Diao B, Wang C, Tan Y, Chen X, Liu Y, Ning L, et al. Reduction and Functional Exhaustion of T Cells in Patients with Coronavirus Disease 2019 (COVID-19). Front Immunol. 2020 May 1; 11:827. doi: 10.3389/fimmu.2020.00827.

Zheng M, Gao Y, Wang G, Song G, Liu S, Sun D, et al. Functional exhaustion of antiviral lymphocytes in COVID-19 patients. Cell Mol Immunol 2020 May, 17(5): 533–535. Doi: 10.1038/s41423-020-0402-2

Jafarzadeh A, Jafarzadeh S, Nozari P, Mokhtari P, Nemati M. Lymphopenia an important immunological abnormality in patients with COVID-19: Possible mechanisms. Scand J Immunol. 2021 Feb;93(2):e12967. doi: 10.1111/sji.12967. Epub 2020 Sep 14.

Mazzoni A, Salvati L, Maggi L, Capone M, Vanni A, Spinicci M, et al. Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent. J Clin Invest. 2020 Sep 1;130(9):4694-4703. doi: 10.1172/JCI138554.

Aguillón J, Escobar A, Ferreira F, Aguirre A, Ferreira L, Molina M, et al. Daily production of human tumor necrosis factor in lipopolysaccharide (LPS)-stimulated ex vivo blood culture assays. Eur Cytokine Netw. 2001 Mar;12(1):105-10.

Cheng ZJ, Huang H, Zheng P, Xue M, Ma J, Zhan Z, et al. Humoral immune response of BBIBP COVID-19 vaccination before and after the booster immunization. Allergy. 2022 Aug;77(8):2404-2414. doi: 10.1111/all.15271. Epub 2022 Mar 16.

Roy S, Coulon PG, Srivastava R, Vahed H, Kim GJ, Walia SS, et al. Blockade of LAG-3 immune checkpoint combined with therapeutic vaccination restore the function of tissue-resident anti-viral CD8+ T cells and protect against recurrent ocular herpes simplex infection and disease. Front Immunol. 2018 Dec 17; 9:2922. doi: 10.3389/fimmu.2018.02922.

Mei Q, Hu G, Yang Y, Liu B, Yin J, Li M, et al. Impact of COVID-19 vaccination on the use of PD-1 inhibitor in treating patients with cancer: A real-world study. J Immunother Cancer 2022 Mar;10(3):e004157. doi:10.1136/jitc-2021-004157.

Published

2024-09-27

How to Cite

1.
Lozada Requena I, Paredes Inofuente D. Level of IgG antibodies, tumor necrosis factor alpha and T-cell exhaustion in persons vaccinated against SARS-CoV-2. Rev Méd Hered [Internet]. 2024 Sep. 27 [cited 2024 Oct. 7];35(3):130-41. Available from: http://44.198.254.164/index.php/RMH/article/view/5258

Issue

Section

ORIGINAL RESEARCH