Proteomic Analysis of Mucosal and Systemic Responses to SARS-CoV-2 Antigen

Overview

Journal Vaccines (Basel)

Date 2023 Feb 28

PMID 36851212

Authors

Neil Martinson

Bhavna Gordhan

Stefan Petkov

Azure-Dee Pillay

Thabiso Seiphetlo

Natasha Singh

Kennedy Otwombe

Limakatso Lebina

Claudia Fredolini

Francesca Chiodi

Julie Fox

Bavesh Kana

Carolina Herrera

Affiliations

Soon will be listed here.

Abstract

The mucosal environment of the upper respiratory tract is the first barrier of protection against SARS-CoV-2 transmission. However, the mucosal factors involved in viral transmission and potentially modulating the capacity to prevent such transmission have not fully been identified. In this pilot proteomics study, we compared mucosal and systemic compartments in a South African cohort of vaccinated and unvaccinated individuals undergoing maxillofacial surgery with previous history of COVID-19 or not. Inflammatory profiles were analyzed in plasma, nasopharyngeal swabs, and nasal and oral tissue explant cultures, using Olink and Luminex technologies. SARS-CoV-2-specific antibody levels were measured in serum and tissue explants. An increased pro-inflammatory proteomic profile was measured in the nasal compartment compared to plasma. However, IP-10 and MIG levels were higher in secretions than in nasal tissue, and the opposite was observed for TGF-β. Nasal anti-SARS-CoV-2 spike IgG correlated with mucosal MIG expression for all participants. A further positive correlation was found with IP-10 in BioNTech/Pfizer-vaccinated individuals. Systemic levels of anti-SARS-CoV-2 spike IgG elicited by this vaccine correlated with plasma IL-10, IL-6 and HBD4. Proteomic profiles measured in mucosal tissues and secretions using combined technologies could reveal correlates of protection at the mucosal portals of viral entry.

Citing Articles

The Impact of Serum/Plasma Proteomics on SARS-CoV-2 Diagnosis and Prognosis.

DAmato M, Grignano M, Iadarola P, Rampino T, Gregorini M, Viglio S Int J Mol Sci. 2024; 25(16).

PMID: 39201322 PMC: 11354567. DOI: 10.3390/ijms25168633.

Evaluation of a human mucosal tissue explant model for SARS-CoV-2 replication.

Gordhan B, Herrera C, Pillay A, Seiphetlo T, Ealand C, Machowski E PLoS One. 2023; 18(9):e0291146.

PMID: 37769001 PMC: 10538748. DOI: 10.1371/journal.pone.0291146.

Cytokine Response Following SARS-CoV-2 Antigen Stimulation in Patients with Predominantly Antibody Deficiencies.

Lucane Z, Slisere B, Gersone G, Papirte S, Gailite L, Tretjakovs P Viruses. 2023; 15(5).

PMID: 37243231 PMC: 10222647. DOI: 10.3390/v15051146.

References

. Note from the editors: World Health Organization declares novel coronavirus (2019-nCoV) sixth public health emergency of international concern. Euro Surveill. 2020; 25(5). PMC: 7014669. DOI: 10.2807/1560-7917.ES.2020.25.5.200131e. View

Assarsson E, Lundberg M, Holmquist G, Bjorkesten J, Thorsen S, Ekman D . Homogenous 96-plex PEA immunoassay exhibiting high sensitivity, specificity, and excellent scalability. PLoS One. 2014; 9(4):e95192. PMC: 3995906. DOI: 10.1371/journal.pone.0095192. View

Herrera C, McRaven M, Laing K, Dennis J, Hope T, Shattock R . Early Colorectal Responses to HIV-1 and Modulation by Antiretroviral Drugs. Vaccines (Basel). 2021; 9(3). PMC: 8000905. DOI: 10.3390/vaccines9030231. View

Ramezanpour M, Bolt H, Hon K, Bouras G, Psaltis A, Wormald P . Cytokine-Induced Modulation of SARS-CoV2 Receptor Expression in Primary Human Nasal Epithelial Cells. Pathogens. 2021; 10(7). PMC: 8308731. DOI: 10.3390/pathogens10070848. View

Wright P, Prevost-Reilly A, Natarajan H, Brickley E, Connor R, Wieland-Alter W . Longitudinal Systemic and Mucosal Immune Responses to SARS-CoV-2 Infection. J Infect Dis. 2022; 226(7):1204-1214. PMC: 8903457. DOI: 10.1093/infdis/jiac065. View

Dos Santos J, Soares C, Monteiro F, Mello R, do Amaral J, Aguiar A . In Nasal Mucosal Secretions, Distinct IFN and IgA Responses Are Found in Severe and Mild SARS-CoV-2 Infection. Front Immunol. 2021; 12:595343. PMC: 7946815. DOI: 10.3389/fimmu.2021.595343. View

Yoshinari T, Hayashi K, Hirose S, Ohya K, Ohnishi T, Watanabe M . Matrix-Assisted Laser Desorption and Ionization Time-of-Flight Mass Spectrometry Analysis for the Direct Detection of SARS-CoV-2 in Nasopharyngeal Swabs. Anal Chem. 2022; 94(10):4218-4226. PMC: 8903212. DOI: 10.1021/acs.analchem.1c04328. View

Vu D, Martinez-Murillo P, Pigny F, Vono M, Meyer B, Eberhardt C . Longitudinal Analysis of Inflammatory Response to SARS-CoV-2 in the Upper Respiratory Tract Reveals an Association with Viral Load, Independent of Symptoms. J Clin Immunol. 2021; 41(8):1723-1732. PMC: 8476983. DOI: 10.1007/s10875-021-01134-z. View

De Cunto G, Lunghi B, Bartalesi B, Cavarra E, Fineschi S, Ulivieri C . Severe Reduction in Number and Function of Peripheral T Cells Does Not Afford Protection toward Emphysema and Bronchial Remodeling Induced in Mice by Cigarette Smoke. Am J Pathol. 2016; 186(7):1814-1824. DOI: 10.1016/j.ajpath.2016.03.002. View

10.

Azzi L, Dalla Gasperina D, Veronesi G, Shallak M, Ietto G, Iovino D . Mucosal immune response in BNT162b2 COVID-19 vaccine recipients. EBioMedicine. 2021; 75:103788. PMC: 8718969. DOI: 10.1016/j.ebiom.2021.103788. View

11.

Ravichandran S, Grubbs G, Tang J, Lee Y, Huang C, Golding H . Systemic and mucosal immune profiling in asymptomatic and symptomatic SARS-CoV-2-infected individuals reveal unlinked immune signatures. Sci Adv. 2021; 7(42):eabi6533. PMC: 8514093. DOI: 10.1126/sciadv.abi6533. View

12.

Joo N, Evans I, Cho H, Park I, Engelhardt J, Wine J . Proteomic analysis of pure human airway gland mucus reveals a large component of protective proteins. PLoS One. 2015; 10(2):e0116756. PMC: 4338240. DOI: 10.1371/journal.pone.0116756. View

13.

Ferrara P, Gianfredi V, Tomaselli V, Polosa R . The Effect of Smoking on Humoral Response to COVID-19 Vaccines: A Systematic Review of Epidemiological Studies. Vaccines (Basel). 2022; 10(2). PMC: 8880575. DOI: 10.3390/vaccines10020303. View

14.

Peng P, Deng H, Li Z, Chen Y, Fang L, Hu J . Distinct immune responses in the early phase to natural SARS-CoV-2 infection or vaccination. J Med Virol. 2022; 94(12):5691-5701. PMC: 9353276. DOI: 10.1002/jmv.28034. View

15.

Mancuso R, Agostini S, Citterio L, Chiarini D, Santangelo M, Clerici M . Systemic and Mucosal Humoral Immune Response Induced by Three Doses of the BNT162b2 SARS-CoV-2 mRNA Vaccines. Vaccines (Basel). 2022; 10(10). PMC: 9610882. DOI: 10.3390/vaccines10101649. View

16.

Pinto G, Illiano A, Ferrucci V, Quarantelli F, Fontanarosa C, Siciliano R . Identification of SARS-CoV-2 Proteins from Nasopharyngeal Swabs Probed by Multiple Reaction Monitoring Tandem Mass Spectrometry. ACS Omega. 2021; 6(50):34945-34953. PMC: 8672425. DOI: 10.1021/acsomega.1c05587. View

17.

Kaur G, Lungarella G, Rahman I . SARS-CoV-2 COVID-19 susceptibility and lung inflammatory storm by smoking and vaping. J Inflamm (Lond). 2020; 17:21. PMC: 7284674. DOI: 10.1186/s12950-020-00250-8. View

18.

Gallo O, Locatello L, Mazzoni A, Novelli L, Annunziato F . The central role of the nasal microenvironment in the transmission, modulation, and clinical progression of SARS-CoV-2 infection. Mucosal Immunol. 2020; 14(2):305-316. PMC: 7690066. DOI: 10.1038/s41385-020-00359-2. View

19.

Butler S, Crowley A, Natarajan H, Xu S, Weiner J, Bobak C . Distinct Features and Functions of Systemic and Mucosal Humoral Immunity Among SARS-CoV-2 Convalescent Individuals. Front Immunol. 2021; 11:618685. PMC: 7876222. DOI: 10.3389/fimmu.2020.618685. View

20.

Gouveia D, Miotello G, Gallais F, Gaillard J, Debroas S, Bellanger L . Proteotyping SARS-CoV-2 Virus from Nasopharyngeal Swabs: A Proof-of-Concept Focused on a 3 Min Mass Spectrometry Window. J Proteome Res. 2020; 19(11):4407-4416. DOI: 10.1021/acs.jproteome.0c00535. View