Login Register Cart 0
Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Perspective

Human Defensins from Antivirals to Vaccine Adjuvants: Rediscovery of the Innate Immunity Arsenal

Author(s): Luisa Zupin* and Sergio Crovella

Volume 29, Issue 2, 2022

Published on: 20 January, 2022

Page: [121 - 124] Pages: 4

DOI: 10.2174/0929866528666211125110058

conference banner
Abstract

Human defensins are a class of antimicrobial peptides, belonging to the innate immunity system. These peptides are expressed at the level of respiratory tract (both upper and lower) where they represent the first line of defense against pathogens; they are also known for their activity against different viruses, acting through diverse mechanisms, including direct binding to the virus, inhibition of viral replication, and aggregation of virions. It has been recently reported they are also effective against SARS-CoV-2. Moreover, they influence the immune response stimulating it in the challenge against microorganisms. An intriguingly potential application of defensin is related to their use as vaccine adjuvants; indeed, some in silico studies suggested their efficacy in boosting the immune response. Since the long-term persistence of acquired immunity against SARS-CoV-2 triggered by the currently employed vaccines is not known, natural agents with enhancing effects, such as defensins, administered with the vaccine, can be an interesting and attractive alternative.

Keywords: Antimicrobial peptides, human defensins, antivirals, vaccine, SARS-CoV-2, immune response.

Next »
Graphical Abstract

[1]
WHO. WHO Coronavirus Disease (COVID-19) Dashboard. Available from: https://covid19.who.int/?gclid=CjwKCAjw26H3BRB2EiwAy32zhYs48QTg_ZzRH8PtKirDGTLO9OXgPmZIcii3enDZbaDtgJ0mDNhGMhoChH8QAvD_BwE (Accessed on: Oct 13, 2021).
[2]
WHO. Coronavirus. 2019, Available from: https://www.who.int/ westernpacific/health-topics/coronavirus (Accessed on: Oct 13, 2021).
[3]
Radia, T.; Williams, N.; Agrawal, P.; Harman, K.; Weale, J.; Cook, J.; Gupta, A. Multi-system inflammatory syndrome in children & adolescents (MIS-C): A systematic review of clinical features and presentation. Paediatr. Respir. Rev., 2021, 38, 51-57.
[PMID: 32891582]
[4]
WHO. COVID-19 vaccines. 2019, Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/covid-19-vaccines (Accessed on: Oct 13, 2021).
[5]
CDC. COVID-19 Vaccines for Children and Teens. 2019, Available from: https://www.cdc.gov/coronavirus/2019-ncov/ vaccines/ recommendations/adolescents.html (Accessed on: Oct 13, 2021).
[6]
EMA. First COVID-19 vaccine approved for children aged 12 to 15 in EU. 2019, Available from: https://www.ema.europa.eu/ en/news/ first-covid-19-vaccine-approved-children-aged-12-15-eu (Accessed on: Oct 13, 2021).
[7]
Rahmani, A.; Baee, M.; Saleki, K.; Moradi, S.; Nouri, H.R. Applying high throughput and comprehensive immunoinformatics approaches to design a trivalent subunit vaccine for induction of immune response against emerging human coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2. J. Biomol. Struct. Dyn., 2021, 29, 1-17.
[PMID: 33509045]
[8]
Safavi, A.; Kefayat, A.; Mahdevar, E.; Abiri, A.; Ghahremani, F. Exploring the out of sight antigens of SARS-CoV-2 to design a candidate multi-epitope vaccine by utilizing immunoinformatics approaches. Vaccine, 2020, 38(48), 7612-7628.
[http://dx.doi.org/10.1016/j.vaccine.2020.10.016] [PMID: 33082015]
[9]
Jyotisha; Singh, S.; Qureshi, I. A. Multi-epitope vaccine against SARS-CoV-2 applying Immunoinformatics and molecular dynamics aimulation approaches. J. Biomol. Struct. Dyn., 2020. [Epub ahead of print].
[10]
Dong, R.; Chu, Z.; Yu, F.; Zha, Y. Contriving multi-epitope subunit of vaccine for COVID-19: Immunoinformatics approaches. Front. Immunol., 2020, 11, 1784.
[http://dx.doi.org/10.3389/fimmu.2020.01784] [PMID: 32849643]
[11]
Yazdani, Z.; Rafiei, A.; Yazdani, M.; Valadan, R. Design an efficient multi-epitope peptide vaccine candidate against SARS-CoV-2: An in silico analysis. Infect. Drug Resist., 2020, 13, 3007-3022.
[http://dx.doi.org/10.2147/IDR.S264573] [PMID: 32943888]
[12]
Ojha, R.; Gupta, N.; Naik, B.; Singh, S.; Verma, V.K.; Prusty, D.; Prajapati, V.K. High throughput and comprehensive approach to develop multiepitope vaccine against minacious COVID-19. Eur. J. Pharm. Sci., 2020, 151, 105375.
[http://dx.doi.org/10.1016/j.ejps.2020.105375] [PMID: 32417398]
[13]
Bowdish, D.M.E.; Davidson, D.J.; Hancock, R.E.W. Immunomodulatory Properties of Defensins and Cathelicidins. In: Antimicrobial Peptides and Human Disease, Series Eds.; Current Topics in Microbiology and Immunology; Shafer, W. M. Ed.; Compans, R. W.; Cooper, M. D.; Honjo, T.; Koprowski, H.; Melchers, F.; Oldstone, M. B. A.; Olsnes, S.; Vogt, P. K.; Wagner, H., Eds.; Springer: Berlin, Heidelberg, 2006; Vol. 306, pp. 27-66.
[http://dx.doi.org/10.1007/3-540-29916-5_2]
[14]
Huan, Y.; Kong, Q.; Mou, H.; Yi, H. Antimicrobial Peptides: Classification, design, application and research progress in multiple fields. Front. Microbiol., 2020, 11, 582779.
[http://dx.doi.org/10.3389/fmicb.2020.582779] [PMID: 33178164]
[15]
Ahmed, A.; Siman-Tov, G.; Hall, G.; Bhalla, N.; Narayanan, A. Human antimicrobial peptides as therapeutics for viral infections. Viruses, 2019, 11(8), 704.
[http://dx.doi.org/10.3390/v11080704] [PMID: 31374901]
[16]
Xu, C.; Wang, A.; Marin, M.; Honnen, W.; Ramasamy, S.; Porter, E.; Subbian, S.; Pinter, A.; Melikyan, G.B.; Lu, W.; Chang, T.L. Human defensins inhibit SARS-CoV-2 infection by blocking viral entry. Viruses, 2021, 13(7), 1246.
[http://dx.doi.org/10.3390/v13071246] [PMID: 34206990]
[17]
Wang, C.; Wang, S.; Li, D.; Wei, D-Q.; Zhao, J.; Wang, J. Human intestinal Defensin 5 inhibits SARS-CoV-2 invasion by cloaking ACE2. Gastroenterology, 2020, 159(3), 1145-1147.e4.
[http://dx.doi.org/10.1053/j.gastro.2020.05.015] [PMID: 32437749]
[18]
Niv, Y. Defensin 5 for prevention of SARS-CoV-2 invasion and Covid-19 disease. Med. Hypotheses, 2020, 143, 110244.
[http://dx.doi.org/10.1016/j.mehy.2020.110244] [PMID: 33017910]
[19]
Zhao, H.; To, K.K.W.; Sze, K-H.; Yung, T.T-M.; Bian, M.; Lam, H.; Yeung, M.L.; Li, C.; Chu, H.; Yuen, K-Y. A broad-spectrum virus- and host-targeting peptide against respiratory viruses including influenza virus and SARS-CoV-2. Nat. Commun., 2020, 11(1), 4252.
[http://dx.doi.org/10.1038/s41467-020-17986-9] [PMID: 32843628]
[20]
Kerget, B.; Kerget, F.; Aksakal, A.; Aşkın, S.; Sağlam, L.; Akgün, M. Evaluation of alpha defensin, IL-1 receptor antagonist, and IL-18 levels in COVID-19 patients with macrophage activation syndrome and acute respiratory distress syndrome. J. Med. Virol., 2021, 93(4), 2090-2098.
[http://dx.doi.org/10.1002/jmv.26589] [PMID: 33038012]
[21]
Abdeen, S.; Bdeir, K.; Abu-Fanne, R.; Maraga, E.; Higazi, M.; Khurram, N.; Feldman, M.; Deshpande, C.; Litzky, L.A.; Heyman, S.N.; Montone, K.T.; Cines, D.B.; Higazi, A.A. Alpha-defensins: Risk factor for thrombosis in COVID-19 infection. Br. J. Haematol., 2021, 194(1), 44-52.
[http://dx.doi.org/10.1111/bjh.17503] [PMID: 34053084]
[22]
Biragyn, A.; Ruffini, P.A.; Leifer, C.A.; Klyushnenkova, E.; Shakhov, A.; Chertov, O.; Shirakawa, A.K.; Farber, J.M.; Segal, D.M.; Oppenheim, J.J.; Kwak, L.W. Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science, 2002, 298(5595), 1025-1029.
[http://dx.doi.org/10.1126/science.1075565] [PMID: 12411706]
[23]
Biragyn, A.; Coscia, M.; Nagashima, K.; Sanford, M.; Young, H.A.; Olkhanud, P. Murine beta-defensin 2 promotes TLR-4/MyD88-mediated and NF-kappaB-dependent atypical death of APCs via activation of TNFR2. J. Leukoc. Biol., 2008, 83(4), 998-1008.
[http://dx.doi.org/10.1189/jlb.1007700] [PMID: 18192488]
[24]
Romano Carratelli, C.; Mazzola, N.; Paolillo, R.; Sorrentino, S.; Rizzo, A. Toll-like receptor-4 (TLR4) mediates human β-defensin-2 (HBD-2) induction in response to Chlamydia pneumoniae in mononuclear cells. FEMS Immunol. Med. Microbiol., 2009, 57(2), 116-124.
[http://dx.doi.org/10.1111/j.1574-695X.2009.00586.x] [PMID: 19735472]
[25]
Kim, J.; Yang, Y.L.; Jang, S-H.; Jang, Y-S. Human β-defensin 2 plays a regulatory role in innate antiviral immunity and is capable of potentiating the induction of antigen-specific immunity. Virol. J., 2018, 15(1), 124.
[http://dx.doi.org/10.1186/s12985-018-1035-2] [PMID: 30089512]
[26]
Perrie, Y.; Mohammed, A.R.; Kirby, D.J.; McNeil, S.E.; Bramwell, V.W. Vaccine adjuvant systems: Enhancing the efficacy of sub-unit protein antigens. Int. J. Pharm., 2008, 364(2), 272-280.
[http://dx.doi.org/10.1016/j.ijpharm.2008.04.036] [PMID: 18555624]
[27]
Funderburg, N.; Lederman, M.M.; Feng, Z.; Drage, M.G.; Jadlowsky, J.; Harding, C.V.; Weinberg, A.; Sieg, S.F. Human -defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2. Proc. Natl. Acad. Sci. USA, 2007, 104(47), 18631-18635.
[http://dx.doi.org/10.1073/pnas.0702130104] [PMID: 18006661]
[28]
Judge, C.J.; Reyes-Aviles, E.; Conry, S.J.; Sieg, S.S.; Feng, Z.; Weinberg, A.; Anthony, D.D. HBD-3 induces NK cell activation, IFN-γ secretion and mDC dependent cytolytic function. Cell. Immunol., 2015, 297(2), 61-68.
[http://dx.doi.org/10.1016/j.cellimm.2015.06.004] [PMID: 26302933]
[29]
Röhrl, J.; Yang, D.; Oppenheim, J. J.; Hehlgans, T. Human β-Defensin 2 and 3 and their mouse orthologs induce chemotaxis through interaction with CCR2. J.I., 2010, 184(12), 6688-6694.
[30]
Gupta, N.; Regar, H.; Verma, V.K.; Prusty, D.; Mishra, A.; Prajapati, V.K. Receptor-ligand based molecular interaction to discover adjuvant for immune cell TLRs to develop next-generation vaccine. Int. J. Biol. Macromol., 2020, 152, 535-545.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.02.297] [PMID: 32112848]
[31]
Kagan, B.L.; Ganz, T.; Lehrer, R.I. Defensins: A family of antimicrobial and cytotoxic peptides. Toxicology, 1994, 87(1-3), 131-149.
[http://dx.doi.org/10.1016/0300-483X(94)90158-9] [PMID: 7512758]
[32]
Shapiro, R. S. COVID-19 vaccines and nanomedicine. Int. J. Dermatol., 2021, 2021, ijd.15673.
[33]
Heinrich, M.A.; Martina, B.; Prakash, J. Nanomedicine strategies to target coronavirus. Nano Today, 2020, 35, 100961.
[http://dx.doi.org/10.1016/j.nantod.2020.100961] [PMID: 32904707]

Rights & Permissions Print Cite
Article Metrics
22
1
© 2024 Bentham Science Publishers | Privacy Policy