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Impact of COVID-19 vaccination on saliva immune barriers: IgA, lysozyme, and lactoferrin

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Abstract

Understanding the role of salivary constituents, such as lactoferrin, lysozyme, and secretory immunoglobulin A (sIgA), in immune protection and defense mechanisms against microbial invasion and colonization of the airways is important in light of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The salivary immune barrier in individuals affected by COVID-19 may contribute to disease prognosis. Thus, the aim of the present review is to evaluate the effect of COVID-19 vaccines on the immunological composition of saliva. IgA antibodies generated by vaccination can neutralize the virus at mucosal surfaces, whereas antimicrobial peptides, such as lysozyme and lactoferrin, have broad-spectrum antimicrobial activity. Collectively, these components contribute to the protective immune response of the oral cavity and may help minimize viral transmission as well as the severity of COVID-19. Measuring the levels of these components in the saliva of COVID-19-vaccinated individuals can help in evaluating the vaccine's ability to induce mucosal immunity, and it might also provide insights into whether saliva can be used in diagnostics or surveillance for monitoring immune responses following vaccination. This also has implications for viral transmission.

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Data availability

The data that support the findings of this study are available from the corresponding author.

References

  1. Actor JK, Hwang S-A, Kruzel ML (2009) Lactoferrin as a natural immune modulator. Curr Pharm Des 15(17):1956–1973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ali AS, Hasan SS, Kow CS, Merchant HA (2021) Lactoferrin reduces the risk of respiratory tract infections: a meta-analysis of randomized controlled trials. Clin Nutr ESPEN 45:26–32

    Article  PubMed  Google Scholar 

  3. Bao L, Zhang C, Dong J, Zhao L, Li Y, Sun J (2020) Oral microbiome and SARS-CoV-2: beware of lung co-infection. Front Microbiol 11:1840

    Article  PubMed  PubMed Central  Google Scholar 

  4. Brandtzaeg P (2013) Secretory immunity with special reference to the oral cavity. J Oral Microbiol 5(1):20401

    Article  CAS  Google Scholar 

  5. Brandtzaeg PER (2007) Do salivary antibodies reliably reflect both mucosal and systemic immunity? Ann N Y Acad Sci 1098(1):288–311

    Article  CAS  PubMed  Google Scholar 

  6. Brice DC, Diamond G (2020) Antiviral activities of human host defense peptides. Curr Med Chem 27(9):1420–1443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Cerutti A, Rescigno M (2008) The biology of intestinal immunoglobulin A responses. Immunity 28(6):740–750. https://doi.org/10.1016/j.immuni.2008.05.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Cervia C, Nilsson J, Zurbuchen Y, Valaperti A, Schreiner J, Wolfensberger A, Raeber ME, Adamo S, Weigang S, Emmenegger M, Hasler S, Bosshard PP, De Cecco E, Bächli E, Rudiger A, Stüssi-Helbling M, Huber LC, Zinkernagel AS, Schaer DJ et al (2021) Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19. J Allergy Clin Immunol 147(2):545-557.e9. https://doi.org/10.1016/j.jaci.2020.10.040

    Article  CAS  PubMed  Google Scholar 

  9. Chai D, Yue Y, Xu W, Dong C, Xiong S (2014) Mucosal co-immunization with AIM2 enhances protective SIgA response and increases prophylactic efficacy of chitosan-DNA vaccine against coxsackievirus B3-induced myocarditis. Hum Vaccine Immunother 10(5):1284–1294. https://doi.org/10.4161/hv.28333

    Article  CAS  Google Scholar 

  10. Chao YX, Rötzschke O, Tan E-K (2020) The role of IgA in COVID-19. Brain Behav Immun 87:182–183. https://doi.org/10.1016/j.bbi.2020.05.057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chen L, Wei B, Di DL (2022) A narrative review of tissue-resident memory T cells and their role in immune surveillance and COVID-19. Eur Rev Med Pharmacol Sci 26(12):4486–4496

    CAS  PubMed  Google Scholar 

  12. Costantini VP, Nguyen K, Lyski Z, Novosad S, Bardossy AC, Lyons AK, Gable P, Kutty PK, Lutgring JD, Brunton A (2022) Development and validation of an enzyme immunoassay for detection and quantification of SARS-CoV-2 salivary IgA and IgG. J Immunol 208(6):1500–1508

    Article  CAS  PubMed  Google Scholar 

  13. Fröberg J, Gillard J, Philipsen R, Lanke K, Rust J, van Tuijl D, Teelen K, Bousema T, Simonetti E, van der Gaast-de Jongh CE (2021) SARS-CoV-2 mucosal antibody development and persistence and their relation to viral load and COVID-19 symptoms. Nat Commun 12(1):5621

    Article  PubMed  PubMed Central  Google Scholar 

  14. Gao Y, Yue Y, Xiong S (2021) An albumin-binding domain peptide confers enhanced immunoprotection against viral myocarditis by CVB3 VP1 vaccine. Front Immunol 12:666594. https://doi.org/10.3389/fimmu.2021.666594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. García-Montoya IA, Cendón TS, Arévalo-Gallegos S, Rascón-Cruz Q (2012) Lactoferrin a multiple bioactive protein: an overview. Biochim Biophys Acta (BBA) Gen Subjects 1820(3):226–236

    Article  Google Scholar 

  16. Hayashi T, To M, Saruta J, Sato C, Yamamoto Y, Kondo Y, Shimizu T, Kamata Y, Tsukinoki K (2017) Salivary lactoferrin is transferred into the brain via the sublingual route. Biosci Biotechnol Biochem 81(7):1300–1304

    Article  CAS  PubMed  Google Scholar 

  17. Hosomi K, Kunisawa J (2020) Impact of the intestinal environment on the immune responses to vaccination. Vaccine 38(44):6959–6965

    Article  CAS  PubMed  Google Scholar 

  18. Huan Y, Kong Q, Mou H, Yi H (2020) Antimicrobial peptides: Classification, design, application and research progress in multiple fields. Front Microbiol 11:2559

    Article  Google Scholar 

  19. Isho B, Abe KT, Zuo M, Jamal AJ, Rathod B, Wang JH, Li Z, Chao G, Rojas OL, Bang YM (2020) Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients. Sci Immunol 5(52):eabe5511

    Article  PubMed  PubMed Central  Google Scholar 

  20. Isho B, Abe KT, Zuo M, Jamal AJ, Rathod B, Wang JH, Li Z, Chao G, Rojas OL, Bang YM, Pu A, Christie-Holmes N, Gervais C, Ceccarelli D, Samavarchi-Tehrani P, Guvenc F, Budylowski P, Li A, Paterson A et al (2020) Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients. Sci Immunol 5(52):eabe5511. https://doi.org/10.1126/sciimmunol.abe5511

    Article  PubMed  PubMed Central  Google Scholar 

  21. Iwasaki A (2016) Exploiting mucosal immunity for antiviral vaccines. Annu Rev Immunol 34:575–608

    Article  CAS  PubMed  Google Scholar 

  22. Jafarzadeh A, Sadeghi M, Karam GA, Vazirinejad R (2010) Salivary IgA and IgE levels in healthy subjects: relation to age and gender. Braz Oral Res 24(1):21–27. https://doi.org/10.1590/S1806-83242010000100004

    Article  PubMed  Google Scholar 

  23. Li H, Limenitakis JP, Greiff V, Yilmaz B, Schären O, Urbaniak C, Zünd M, Lawson MAE, Young ID, Rupp S (2020) Mucosal or systemic microbiota exposures shape the B cell repertoire. Nature 584(7820):274–278

    Article  CAS  PubMed  Google Scholar 

  24. Liao H-Y, Wang S-C, Ko Y-A, Lin K-I, Ma C, Cheng T-JR, Wong C-H (2020) Chimeric hemagglutinin vaccine elicits broadly protective CD4 and CD8 T cell responses against multiple influenza strains and subtypes. Proc Natl Acad Sci 117(30):17757–17763. https://doi.org/10.1073/pnas.2004783117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Mao J, Eom G-D, Yoon K-W, Kang H-J, Chu K-B, Quan F-S (2022) Sublingual vaccination with live influenza virus induces better protection than oral immunization in mice. Life 12(7):975. https://doi.org/10.3390/life12070975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ali D, Taha G (2023) Effect of Covid-19 vaccine on some immunological salivary biomarkers (sIgA and Interleukine-17). J Fac Med Baghd 65(2):86–92

    Google Scholar 

  27. Mohn KG-I, Brokstad KA, Pathirana RD, Bredholt G, Jul-Larsen Å, Trieu MC, Lartey SL, Montemoli E, Tøndel C, Aarstad HJ, Cox RJ (2016) Live attenuated influenza vaccine in children induces B-cell responses in tonsils. J Infect Dis 214(5):722–731. https://doi.org/10.1093/infdis/jiw230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Patel J, Sampson V (2020) The role of oral bacteria in COVID-19. Lancet Microbe 1(3):e105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Pisanic N, Randad PR, Kruczynski K, Manabe YC, Thomas DL, Pekosz A, Klein SL, Betenbaugh MJ, Clarke WA, Laeyendecker O, Caturegli PP, Larman HB, Detrick B, Fairley JK, Sherman AC, Rouphael N, Edupuganti S, Granger DA, Granger SW et al (2020) COVID-19 serology at population scale: SARS-CoV-2-specific antibody responses in saliva. J Clin Microbiol 59(1):e02204-20. https://doi.org/10.1128/JCM.02204-20

    Article  PubMed  PubMed Central  Google Scholar 

  30. Presti S, Manti S, Parisi GF, Papale M, Barbagallo IA, Li Volti G, Leonardi S (2021) Lactoferrin: cytokine modulation and application in clinical practice. J Clin Med 10(23):5482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Pursel VG (2021) Modification of production traits. Animal breeding. Routledge, London, pp 183–200

    Chapter  Google Scholar 

  32. Ragland SA, Criss AK (2017) From bacterial killing to immune modulation: recent insights into the functions of lysozyme. PLoS Pathog 13(9):e1006512

    Article  PubMed  PubMed Central  Google Scholar 

  33. Rangel-Ramírez VV, Macías-Piña KA, Servin-Garrido RR, de Alba-Aguayo DR, Moreno-Fierros L, Rubio-Infante N (2022) A systematic review and meta-analysis of the IgA seroprevalence in COVID-19 patients: Is there a role for IgA in COVID-19 diagnosis or severity? Microbiol Res 263:127105. https://doi.org/10.1016/j.micres.2022.127105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ruan X, Luo J, Zhang P, Howell K (2022) The salivary microbiome shows a high prevalence of core bacterial members yet variability across human populations. Npj Biofilms Microbiomes 8(1):85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Sanchez L, Calvo M, Brock JH (1992) Biological role of lactoferrin. Arch Dis Child 67(5):657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Shafqat F, Rehman SU, Niaz K (2022) Lactoferrin can attenuate SARS-CoV-2: An analysis of evidential relations. Biomed Res Ther 9(2):4901–4919

    Article  Google Scholar 

  37. Shi Y, Wang G, Cai X, Deng J, Zheng L, Zhu H, Zheng M, Yang B, Chen Z (2020) An overview of COVID-19. J Zhejiang Univ Sci B 21(5):343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Sri Santosh T, Parmar R, Anand H, Srikanth K, Saritha M (2020) A review of salivary diagnostics and its potential implication in detection of Covid-19. Cureus. https://doi.org/10.7759/cureus.7708

    Article  PubMed  PubMed Central  Google Scholar 

  39. Uehara O, Abiko Y, Nagasawa T, Morikawa T, Hiraki D, Harada F, Kawano Y, Toraya S, Matsuoka H, Paudel D, Shimizu S, Yoshida K, Asaka M, Furuichi Y, Miura H (2022) Alterations in the oral microbiome of individuals with a healthy oral environment following COVID-19 vaccination. BMC Oral Health 22(1):1–9. https://doi.org/10.1186/s12903-022-02093-6

    Article  CAS  Google Scholar 

  40. Wang Z, Lorenzi JCC, Muecksch F, Finkin S, Viant C, Gaebler C, Cipolla M, Hoffmann H-H, Oliveira TY, Oren DA (2021) Enhanced SARS-CoV-2 neutralization by dimeric IgA. Sci Transl Med 13(577):eabf1555

    Article  CAS  PubMed  Google Scholar 

  41. Wang Z, Schmidt F, Weisblum Y, Muecksch F, Barnes CO, Finkin S, Schaefer-Babajew D, Cipolla M, Gaebler C, Lieberman JA (2021) mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants (preprint)

  42. Woods CM, Hooper DN, Ooi EH, Tan L-W, Carney AS (2011) Human lysozyme has fungicidal activity against nasal fungi. Am J Rhinol Allergy 25(4):236–240

    Article  PubMed  Google Scholar 

  43. Wyllie AL, Fournier J, Casanovas-Massana A, Campbell M, Tokuyama M, Vijayakumar P, Warren JL, Geng B, Muenker MC, Moore AJ (2020) Saliva or nasopharyngeal swab specimens for detection of SARS-CoV-2. N Engl J Med 383(13):1283–1286

    Article  PubMed  Google Scholar 

  44. Xiang Z, Koo H, Chen Q, Zhou X, Liu Y, Simon-Soro A (2021) Potential implications of SARS-CoV-2 oral infection in the host microbiota. J Oral Microbiol 13(1):1853451

    Article  Google Scholar 

  45. Yamamoto K (2022) Adverse effects of COVID-19 vaccines and measures to prevent them. Virol J 19(1):1–3

    Article  Google Scholar 

  46. Yamamoto Y, To M, Hayashi T, Shimizu T, Kamata Y, Saruta J, Takahashi T, Tsukinoki K (2015) Intake of indigestible carbohydrates influences IgA response and polymeric Ig receptor expression in the rat submandibular gland. Br J Nutr 113(12):1895–1902

    Article  CAS  PubMed  Google Scholar 

  47. Zhang Y, Lu C, Zhang J (2021) Lactoferrin and its detection methods: a review. Nutrients 13(8):2492. https://doi.org/10.3390/nu13082492

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Zhang Z, Zhang G, Guo M, Tao W, Liu X, Wei H, Jin T, Zhang Y, Zhu S (2021) The potential role of an aberrant mucosal immune response to SARS-CoV-2 in the pathogenesis of IgA nephropathy. Pathogens 10(7):881. https://doi.org/10.3390/pathogens10070881

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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University of Basrah, 2023.

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Correspondence to Marwan Y. Al-Maqtoofi.

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Abdul-Kareem, H.H., Al-Maqtoofi, M.Y. & Burghal, A.A. Impact of COVID-19 vaccination on saliva immune barriers: IgA, lysozyme, and lactoferrin. Arch Virol 168, 293 (2023). https://doi.org/10.1007/s00705-023-05914-3

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