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01-12-2023 | SARS-CoV-2 | Review

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

Authors: Hanadi H. Abdul-Kareem, Marwan Y. Al-Maqtoofi, Ahmed A. Burghal

Published in: Archives of Virology | Issue 12/2023

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.

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

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 45:26–32CrossRefPubMed

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 11:1840CrossRefPubMedPubMedCentral

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

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

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

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

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.2020.10.040CrossRefPubMed

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.28333CrossRef

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.2020.05.057CrossRefPubMedPubMedCentral

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):4486–4496PubMed

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):1500–1508CrossRefPubMed

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):5621CrossRefPubMedPubMedCentral

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.2021.666594CrossRefPubMedPubMedCentral

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):226–236CrossRef

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):1300–1304CrossRefPubMed

17.

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

18.

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

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):eabe5511CrossRefPubMedPubMedCentral

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.abe5511CrossRefPubMedPubMedCentral

21.

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

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/S1806-83242010000100004CrossRefPubMed

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):274–278CrossRefPubMed

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.2004783117CrossRefPubMedPubMedCentral

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/life12070975CrossRefPubMedPubMedCentral

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

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/jiw230CrossRefPubMedPubMedCentral

28.

Patel J, Sampson V (2020) The role of oral bacteria in COVID-19. Lancet Microbe 1(3):e105CrossRefPubMedPubMedCentral

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.02204-20CrossRefPubMedPubMedCentral

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):5482CrossRefPubMedPubMedCentral

31.

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

32.

Ragland SA, Criss AK (2017) From bacterial killing to immune modulation: recent insights into the functions of lysozyme. PLoS Pathog 13(9):e1006512CrossRefPubMedPubMedCentral

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.2022.127105CrossRefPubMedPubMedCentral

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):85CrossRefPubMedPubMedCentral

35.

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

36.

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

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):343CrossRefPubMedPubMedCentral

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.7708CrossRefPubMedPubMedCentral

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/s12903-022-02093-6CrossRef

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):eabf1555CrossRefPubMed

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):236–240CrossRefPubMed

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):1283–1286CrossRefPubMed

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):1853451CrossRef

45.

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

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):1895–1902CrossRefPubMed

47.

Zhang Y, Lu C, Zhang J (2021) Lactoferrin and its detection methods: a review. Nutrients 13(8):2492. https://doi.org/10.3390/nu13082492CrossRefPubMedPubMedCentral

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/pathogens10070881CrossRefPubMedPubMedCentral

Title: Impact of COVID-19 vaccination on saliva immune barriers: IgA, lysozyme, and lactoferrin
Authors: Hanadi H. Abdul-Kareem
Marwan Y. Al-Maqtoofi
Ahmed A. Burghal
Publication date: 01-12-2023
Publisher: Springer Vienna
Keywords: SARS-CoV-2
Vaccination
COVID-19 Vaccination
COVID-19
Published in: Archives of Virology / Issue 12/2023
Print ISSN: 0304-8608
Electronic ISSN: 1432-8798
DOI: https://doi.org/10.1007/s00705-023-05914-3

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