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Virology Journal
Published in: Virology Journal 1/2023

Open Access 01-12-2023 | Vaccination | Research

Antibody induction and immune response in nasal cavity by third dose of SARS-CoV-2 mRNA vaccination

Authors: Aya Ishizaka, Michiko Koga, Taketoshi Mizutani, Ryuta Uraki, Seiya Yamayoshi, Kiyoko Iwatsuki-Horimoto, Shinya Yamamoto, Masaki Imai, Takeya Tsutsumi, Yutaka Suzuki, Yoshihiro Kawaoka, Hiroshi Yotsuyanagi

Published in: Virology Journal | Issue 1/2023

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Abstract

Background

The mucosa serves as the first defence against pathogens and facilitates the surveillance and elimination of symbiotic bacteria by mucosal immunity. Recently, the mRNA vaccine against SARS-CoV-2 has been demonstrated to induce secretory antibodies in the oral and nasal cavities in addition to a systemic immune response. However, the mechanism of induced immune stimulation effect on mucosal immunity and commensal bacteria profile remains unclear.

Methods

Here, we longitudinally analysed the changing nasal microbiota and both systemic and nasal immune response upon SARS-CoV-2 mRNA vaccination, and evaluated how mRNA vaccination influenced nasal microbiota in 18 healthy participants who had received the third BNT162b.

Results

The nasal S-RBD IgG level correlated significantly with plasma IgG levels until 1 month and the levels were sustained for 3 months post-vaccination. In contrast, nasal S-RBD IgA induction peaked at 1 month, albeit slightly, and correlated only with plasma IgA, but the induction level decreased markedly at 3 months post-vaccination. 16 S rRNA sequencing of the nasal microbiota post-vaccination revealed not an overall change, but a decrease in certain opportunistic bacteria, mainly Fusobacterium. The decrease in these bacteria was more pronounced in those who exhibited nasal S-RBD IgA induction, and those with higher S-RBD IgA induction had lower relative amounts of potentially pathogenic bacteria such as Pseudomonas pre-vaccination. In addition, plasma and mucosal S-RBD IgG levels correlated with decreased commensal pathogens such as Finegoldia.

Conclusions

These findings suggest that the third dose of SARS-CoV-2 mRNA vaccination induced S-RBD antibodies in the nasal mucosa and may have stimulated mucosal immunity against opportunistic bacterial pathogens. This effect, albeit probably secondary, may be considered one of the benefits of mRNA vaccination. Furthermore, our data suggest that a cooperative function of mucosal and systemic immunity in the reduction of bacteria and provides a better understanding of the symbiotic relationship between the host and bacteria in the nasal mucosa.
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Literature
1.
Guo L, Ren L, Yang S, Xiao M, Chang D, Yang F, Dela Cruz CS, Wang Y, Wu C, Xiao Y, et al. Profiling early humoral response to diagnose Novel Coronavirus Disease (COVID-19). Clin Infect Dis. 2020;71:778–85.PubMed
2.
Long QX, Liu BZ, Deng HJ, Wu GC, Deng K, Chen YK, Liao P, Qiu JF, Lin Y, Cai XF, et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. 2020;26:845–8.PubMed
3.
Okba NMA, Muller MA, Li W, Wang C, GeurtsvanKessel CH, Corman VM, Lamers MM, Sikkema RS, de Bruin E, Chandler FD, et al. Severe Acute Respiratory Syndrome Coronavirus 2-Specific antibody responses in Coronavirus Disease Patients. Emerg Infect Dis. 2020;26:1478–88.PubMedPubMedCentral
4.
Ceron JJ, Lamy E, Martinez-Subiela S, Lopez-Jornet P, Capela ESF, Eckersall PD, Tvarijonaviciute A. Use of Saliva for diagnosis and monitoring the SARS-CoV-2: a General Perspective. J Clin Med 2020, 9.
5.
Isho B, Abe KT, Zuo M, Jamal AJ, Rathod B, Wang JH, Li Z, Chao G, Rojas OL, Bang YM et al. Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in COVID-19 patients. Sci Immunol 2020, 5.
6.
Chavda VP, Soni S, Vora LK, Soni S, Khadela A, Ajabiya J. mRNA-Based vaccines and therapeutics for COVID-19 and future pandemics. Vaccines (Basel) 2022, 10.
7.
Azzi L, Dalla Gasperina D, Veronesi G, Shallak M, Ietto G, Iovino D, Baj A, Gianfagna F, Maurino V, Focosi D, et al. Mucosal immune response in BNT162b2 COVID-19 vaccine recipients. EBioMedicine. 2022;75:103788.PubMed
8.
Cagigi A, Yu M, Osterberg B, Svensson J, Falck-Jones S, Vangeti S, Ahlberg E, Azizmohammadi L, Warnqvist A, Falck-Jones R et al. Airway antibodies emerge according to COVID-19 severity and wane rapidly but reappear after SARS-CoV-2 vaccination. JCI Insight 2021, 6.
9.
Ketas TJ, Chaturbhuj D, Portillo VMC, Francomano E, Golden E, Chandrasekhar S, Debnath G, Diaz-Tapia R, Yasmeen A, Kramer KD, et al. Antibody responses to SARS-CoV-2 mRNA vaccines are detectable in Saliva. Pathog Immun. 2021;6:116–34.PubMedPubMedCentral
10.
Mades A, Chellamathu P, Kojima N, Lopez L, MacMullan MA, Denny N, Angel AN, Santacruz M, Casian JG, Brobeck M, et al. Detection of persistent SARS-CoV-2 IgG antibodies in oral mucosal fluid and upper respiratory tract specimens following COVID-19 mRNA vaccination. Sci Rep. 2021;11:24448.PubMedPubMedCentral
11.
Planas D, Bruel T, Grzelak L, Guivel-Benhassine F, Staropoli I, Porrot F, Planchais C, Buchrieser J, Rajah MM, Bishop E, et al. Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies. Nat Med. 2021;27:917–24.PubMed
12.
Sano K, Bhavsar D, Singh G, Floda D, Srivastava K, Gleason C, Group PS, Carreno JM, Simon V, Krammer F. SARS-CoV-2 vaccination induces mucosal antibody responses in previously infected individuals. Nat Commun. 2022;13:5135.PubMedPubMedCentral
13.
Sheikh-Mohamed S, Isho B, Chao GYC, Zuo M, Cohen C, Lustig Y, Nahass GR, Salomon-Shulman RE, Blacker G, Fazel-Zarandi M, et al. Systemic and mucosal IgA responses are variably induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection against subsequent infection. Mucosal Immunol. 2022;15:799–808.PubMedPubMedCentral
14.
Tang J, Zeng C, Cox TM, Li C, Son YM, Cheon IS, Wu Y, Behl S, Taylor JJ, Chakaraborty R, et al. Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination. Sci Immunol. 2022;7:eadd4853.PubMed
15.
Sheikh-Mohamed S, Sanders EC, Gommerman JL, Tal MC. Guardians of the oral and nasopharyngeal galaxy: IgA and protection against SARS-CoV-2 infection. Immunol Rev. 2022;309:75–85.PubMedPubMedCentral
16.
17.
Smith N, Goncalves P, Charbit B, Grzelak L, Beretta M, Planchais C, Bruel T, Rouilly V, Bondet V, Hadjadj J, et al. Distinct systemic and mucosal immune responses during acute SARS-CoV-2 infection. Nat Immunol. 2021;22:1428–39.PubMedPubMedCentral
18.
Liu J, Liu S, Zhang Z, Lee X, Wu W, Huang Z, Lei Z, Xu W, Chen D, Wu X, et al. Association between the nasopharyngeal microbiome and metabolome in patients with COVID-19. Synth Syst Biotechnol. 2021;6:135–43.PubMedPubMedCentral
19.
Giugliano R, Sellitto A, Ferravante C, Rocco T, D’Agostino Y, Alexandrova E, Lamberti J, Palumbo D, Galdiero M, Vaccaro E, et al. NGS analysis of nasopharyngeal microbiota in SARS-CoV-2 positive patients during the first year of the pandemic in the Campania Region of Italy. Microb Pathog. 2022;165:105506.PubMedPubMedCentral
20.
Yeoh YK, Zuo T, Lui GC, Zhang F, Liu Q, Li AY, Chung AC, Cheung CP, Tso EY, Fung KS, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021;70:698–706.PubMed
21.
Mizutani T, Ishizaka A, Koga M, Ikeuchi K, Saito M, Adachi E, Yamayoshi S, Iwatsuki-Horimoto K, Yasuhara A, Kiyono H, et al. Correlation analysis between gut microbiota alterations and the Cytokine response in patients with Coronavirus Disease during hospitalization. Microbiol Spectr. 2022;10:e0168921.PubMed
22.
Grasselli G, Scaravilli V, Mangioni D, Scudeller L, Alagna L, Bartoletti M, Bellani G, Biagioni E, Bonfanti P, Bottino N, et al. Hospital-Acquired Infections in critically ill patients with COVID-19. Chest. 2021;160:454–65.PubMed
23.
Bernard-Raichon L, Venzon M, Klein J, Axelrad JE, Zhang C, Sullivan AP, Hussey GA, Casanovas-Massana A, Noval MG, Valero-Jimenez AM, et al. Gut microbiome dysbiosis in antibiotic-treated COVID-19 patients is associated with microbial translocation and bacteremia. Nat Commun. 2022;13:5926.PubMedPubMedCentral
24.
Lunken GR, Golding L, Schick A, Majdoubi A, Lavoie PM, Vallance BA. Gut microbiome and dietary fibre intake strongly associate with IgG function and maturation following SARS-CoV-2 mRNA vaccination. Gut 2022.
25.
Ng SC, Peng Y, Zhang L, Mok CK, Zhao S, Li A, Ching JY, Liu Y, Yan S, Chan DLS, et al. Gut microbiota composition is associated with SARS-CoV-2 vaccine immunogenicity and adverse events. Gut. 2022;71:1106–16.PubMed
26.
Seong H, Choi BK, Han YH, Kim JH, Gim JA, Lim S, Noh JY, Cheong HJ, Kim WJ, Song JY. Gut microbiota as a potential key to modulating humoral immunogenicity of new platform COVID-19 vaccines. Signal Transduct Target Ther. 2023;8:178.PubMedPubMedCentral
27.
Chen K, Magri G, Grasset EK, Cerutti A. Rethinking mucosal antibody responses: IgM, IgG and IgD join IgA. Nat Rev Immunol. 2020;20:427–41.PubMedPubMedCentral
28.
Oh JZ, Ravindran R, Chassaing B, Carvalho FA, Maddur MS, Bower M, Hakimpour P, Gill KP, Nakaya HI, Yarovinsky F, et al. TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination. Immunity. 2014;41:478–92.PubMedPubMedCentral
29.
Klindworth A, Pruesse E, Schweer T, Peplies J, Quast C, Horn M, Glockner FO. Evaluation of general 16S ribosomal RNA gene PCR primers for classical and next-generation sequencing-based diversity studies. Nucleic Acids Res. 2013;41:e1.PubMed
30.
Bolyen E, Rideout JR, Dillon MR, Bokulich NA, Abnet CC, Al-Ghalith GA, Alexander H, Alm EJ, Arumugam M, Asnicar F, et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol. 2019;37:852–7.PubMedPubMedCentral
31.
Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJ, Holmes SP. DADA2: high-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13:581–3.PubMedPubMedCentral
32.
Quast C, Pruesse E, Yilmaz P, Gerken J, Schweer T, Yarza P, Peplies J, Glockner FO. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res. 2013;41:D590–596.PubMed
33.
Fabian Pedregosa GV, Alexandre Gramfort V, Michel B, Thirion O, Grisel M, Blondel A, Müller J, Nothman G, Louppe P, Prettenhofer R, Weiss. Vincent Dubourg, Jake Vanderplas, Alexandre Passos, David Cournapeau, Matthieu Brucher, Matthieu Perrot, Édouard Duchesnay: Scikit-learn: machine learning in Python. J Mach Learn Res. 2011;12:2825–30.
34.
Kaul A, Mandal S, Davidov O, Peddada SD. Analysis of Microbiome Data in the Presence of excess Zeros. Front Microbiol. 2017;8:2114.PubMedPubMedCentral
35.
Escapa IF, Chen T, Huang Y, Gajare P, Dewhirst FE, Lemon KP. New Insights into Human Nostril Microbiome from the Expanded Human Oral Microbiome Database (eHOMD): a Resource for the Microbiome of the Human Aerodigestive Tract. mSystems 2018, 3.
36.
Guerrieri M, Francavilla B, Fiorelli D, Nuccetelli M, Passali FM, Coppeta L, Somma G, Bernardini S, Magrini A, Di Girolamo S. Nasal and salivary mucosal humoral Immune Response elicited by mRNA BNT162b2 COVID-19 vaccine compared to SARS-CoV-2 Natural infection. Vaccines (Basel) 2021, 9.
37.
Kau AL, Planer JD, Liu J, Rao S, Yatsunenko T, Trehan I, Manary MJ, Liu TC, Stappenbeck TS, Maleta KM, et al. Functional characterization of IgA-targeted bacterial taxa from undernourished malawian children that produce diet-dependent enteropathy. Sci Transl Med. 2015;7:276ra224.
38.
Ost KS, O’Meara TR, Stephens WZ, Chiaro T, Zhou H, Penman J, Bell R, Catanzaro JR, Song D, Singh S, et al. Adaptive immunity induces mutualism between commensal eukaryotes. Nature. 2021;596:114–8.PubMedPubMedCentral
39.
Palm NW, de Zoete MR, Cullen TW, Barry NA, Stefanowski J, Hao L, Degnan PH, Hu J, Peter I, Zhang W, et al. Immunoglobulin a coating identifies colitogenic bacteria in inflammatory bowel disease. Cell. 2014;158:1000–10.PubMedPubMedCentral
40.
Sutherland DB, Suzuki K, Fagarasan S. Fostering of advanced mutualism with gut microbiota by Immunoglobulin A. Immunol Rev. 2016;270:20–31.PubMed
41.
Koch MA, Reiner GL, Lugo KA, Kreuk LS, Stanbery AG, Ansaldo E, Seher TD, Ludington WB, Barton GM. Maternal IgG and IgA antibodies dampen mucosal T helper cell responses in early life. Cell. 2016;165:827–41.PubMedPubMedCentral
42.
Ohsaki A, Venturelli N, Buccigrosso TM, Osganian SK, Lee J, Blumberg RS, Oyoshi MK. Maternal IgG immune complexes induce food allergen-specific tolerance in offspring. J Exp Med. 2018;215:91–113.PubMedPubMedCentral
43.
Zeng MY, Cisalpino D, Varadarajan S, Hellman J, Warren HS, Cascalho M, Inohara N, Nunez G. Gut Microbiota-Induced Immunoglobulin G Controls systemic infection by symbiotic Bacteria and pathogens. Immunity. 2016;44:647–58.PubMedPubMedCentral
44.
Wang YY, Harit D, Subramani DB, Arora H, Kumar PA, Lai SK. Influenza-binding antibodies immobilise influenza viruses in fresh human airway mucus. Eur Respir J 2017, 49.
45.
Xu F, Newby JM, Schiller JL, Schroeder HA, Wessler T, Chen A, Forest MG, Lai SK. Modeling Barrier Properties of intestinal mucus Reinforced with IgG and secretory IgA against motile Bacteria. ACS Infect Dis. 2019;5:1570–80.PubMed
46.
Fadlallah J, Sterlin D, Fieschi C, Parizot C, Dorgham K, El Kafsi H, Autaa G, Ghillani-Dalbin P, Juste C, Lepage P, et al. Synergistic convergence of microbiota-specific systemic IgG and secretory IgA. J Allergy Clin Immunol. 2019;143:1575–1585e1574.PubMed
47.
Lucijanic M, Cikara T, Bistrovic P, Papic I, Ortner Hadziabdic M, Busic N, Lackovic M, Cesar N, Koscak V, Mitrovic J, et al. Remdesivir use in COVID-19 patients might predispose bacteremia, matched case-control analysis. J Infect. 2022;85:174–211.PubMedPubMedCentral
48.
Rhoades NS, Pinski AN, Monsibais AN, Jankeel A, Doratt BM, Cinco IR, Ibraim I, Messaoudi I. Acute SARS-CoV-2 infection is associated with an increased abundance of bacterial pathogens, including Pseudomonas aeruginosa in the nose. Cell Rep. 2021;36:109637.PubMedPubMedCentral
49.
Rosas-Salazar C, Kimura KS, Shilts MH, Strickland BA, Freeman MH, Wessinger BC, Gupta V, Brown HM, Rajagopala SV, Turner JH, Das SR. SARS-CoV-2 infection and viral load are associated with the upper respiratory tract microbiome. J Allergy Clin Immunol. 2021;147:1226–1233e1222.PubMedPubMedCentral
50.
Lehtinen MJ, Hibberd AA, Mannikko S, Yeung N, Kauko T, Forssten S, Lehtoranta L, Lahtinen SJ, Stahl B, Lyra A, Turner RB. Nasal microbiota clusters associate with inflammatory response, viral load, and symptom severity in experimental rhinovirus challenge. Sci Rep. 2018;8:11411.PubMedPubMedCentral
51.
Han Y, Wang B, Gao H, He C, Hua R, Liang C, Xin S, Wang Y, Xu J. Insight into the Relationship between Oral Microbiota and the Inflammatory Bowel Disease. Microorganisms 2022, 10.
52.
Takahashi Y, Watanabe N, Kamio N, Yokoe S, Suzuki R, Sato S, Iinuma T, Imai K. Expression of the SARS-CoV-2 receptor ACE2 and Proinflammatory Cytokines Induced by the Periodontopathic Bacterium Fusobacterium nucleatum in Human respiratory epithelial cells. Int J Mol Sci 2021, 22.
53.
Peace O, Rachakonda K, Kress M, Villalta F, Rachakonda G. Respiratory and neurological disease across different ethnic groups is influenced by the Microbiome. Microorganisms 2021, 9.
Metadata
Title
Antibody induction and immune response in nasal cavity by third dose of SARS-CoV-2 mRNA vaccination
Authors
Aya Ishizaka
Michiko Koga
Taketoshi Mizutani
Ryuta Uraki
Seiya Yamayoshi
Kiyoko Iwatsuki-Horimoto
Shinya Yamamoto
Masaki Imai
Takeya Tsutsumi
Yutaka Suzuki
Yoshihiro Kawaoka
Hiroshi Yotsuyanagi
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2023
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-023-02113-z

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