{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:15:24Z","timestamp":1787030124069,"version":"build-2736575974"},"reference-count":53,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T00:00:00Z","timestamp":1668556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The recent outbreak of Monkeypox virus requires the development of a vaccine specifically directed against this virus as quickly as possible. We propose here a new strategy based on a two-step analysis combining (i) the search for binding domains of viral proteins to gangliosides present in lipid rafts of host cells, and (ii) B epitope predictions. Based on previous studies of HIV and SARS-CoV-2 proteins, we show that the Monkeypox virus cell surface-binding protein E8L possesses a ganglioside-binding motif consisting of several subsites forming a ring structure. The binding of the E8L protein to a cluster of gangliosides GM1 mimicking a lipid raft domain is driven by both shape and electrostatic surface potential complementarities. An induced-fit mechanism unmasks selected amino acid side chains of the motif without significantly affecting the secondary structure of the protein. The ganglioside-binding motif overlaps three potential linear B epitopes that are well exposed on the unbound E8L surface that faces the host cell membrane. This situation is ideal for generating neutralizing antibodies. We thus suggest using these three sequences derived from the E8L protein as immunogens in a vaccine formulation (recombinant protein, synthetic peptides or genetically based) specific for Monkeypox virus. This lipid raft\/ganglioside-based strategy could be used for developing therapeutic and vaccine responses to future virus outbreaks, in parallel to existing solutions.<\/jats:p>","DOI":"10.3390\/v14112531","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T02:31:27Z","timestamp":1668565887000},"page":"2531","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["A Vaccine Strategy Based on the Identification of an Annular Ganglioside Binding Motif in Monkeypox Virus Protein E8L"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8653-5521","authenticated-orcid":false,"given":"Jacques","family":"Fantini","sequence":"first","affiliation":[{"name":"INSERM UMR_S-1072 and Faculty of Medicine, Aix-Marseille Universit\u00e9, Boulevard Pierre Dramard, 13015 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri","family":"Chahinian","sequence":"additional","affiliation":[{"name":"INSERM UMR_S-1072 and Faculty of Medicine, Aix-Marseille Universit\u00e9, Boulevard Pierre Dramard, 13015 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nouara","family":"Yahi","sequence":"additional","affiliation":[{"name":"INSERM UMR_S-1072 and Faculty of Medicine, Aix-Marseille Universit\u00e9, Boulevard Pierre Dramard, 13015 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2392","DOI":"10.1002\/rmv.2392","article-title":"Monkeypox: An international epidemic","volume":"32","author":"Focosi","year":"2022","journal-title":"Rev. Med. Virol."},{"key":"ref_2","unstructured":"CDC (2022, October 10). Monkeypox: Vaccine Considerations, Available online: https:\/\/www.cdc.gov\/poxvirus\/monkeypox\/clinicians\/vaccines\/vaccine-considerations.html."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"734","DOI":"10.15585\/mmwr.mm7122e1","article-title":"Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination of Persons at Risk for Occupational Exposure to Orthopoxviruses: Recommendations of the Advisory Committee on Immunization Practices\u2014United States","volume":"71","author":"Rao","year":"2022","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1517\/13543784.17.4.555","article-title":"ACAM2000: A newly licensed cell culture-based live vaccinia smallpox vaccine","volume":"17","author":"Greenberg","year":"2008","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"See, K.C. (2022). Vaccination for Monkeypox Virus Infection in Humans: A Review of Key Considerations. Vaccines, 10.","DOI":"10.3390\/vaccines10081342"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/1743-422X-6-188","article-title":"Inhibition of monkeypox virus replication by RNA interference","volume":"6","author":"Alkhalil","year":"2009","journal-title":"Virol. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8750","DOI":"10.1128\/JVI.73.10.8750-8761.1999","article-title":"Vaccinia virus envelope D8L protein binds to cell surface chondroitin sulfate and mediates the adsorption of intracellular mature virions to cells","volume":"73","author":"Hsiao","year":"1999","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.jinf.2021.06.001","article-title":"Structural dynamics of SARS-CoV-2 variants: A health monitoring strategy for anticipating COVID-19 outbreaks","volume":"83","author":"Fantini","year":"2021","journal-title":"J. Infect."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/bs.apcsb.2021.08.003","article-title":"Ganglioside binding domains in proteins: Physiological and pathological mechanisms","volume":"128","author":"Azzaz","year":"2022","journal-title":"Adv. Protein Chem. Struct. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.bbrc.2020.10.015","article-title":"Leveraging coronavirus binding to gangliosides for innovative vaccine and therapeutic strategies against COVID-19","volume":"538","author":"Fantini","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Verma, D.K., Gupta, D., and Lal, S.K. (2018). Host Lipid Rafts Play a Major Role in Binding and Endocytosis of Influenza A Virus. Viruses, 10.","DOI":"10.3390\/v10110650"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103436","DOI":"10.1016\/j.etap.2020.103436","article-title":"Dual function of sialic acid in gastrointestinal SARS-CoV-2 infection","volume":"79","author":"Engin","year":"2020","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"618296","DOI":"10.3389\/fcell.2020.618296","article-title":"Targeting Lipid Rafts as a Strategy Against Coronavirus","volume":"8","author":"Sorice","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s10719-006-5433-0","article-title":"Role of sialic acid-containing molecules in paramyxovirus entry into the host cell: A minireview","volume":"23","author":"Villar","year":"2006","journal-title":"Glycoconj. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/s41589-021-00924-1","article-title":"Sialic acid-containing glycolipids mediate binding and viral entry of SARS-CoV-2","volume":"18","author":"Nguyen","year":"2022","journal-title":"Nat. Chem. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/978-1-0716-2635-1_14","article-title":"Solid-Phase Binding Assay for Ganglioside Binding of Human Respiroviruses","volume":"2556","author":"Suzuki","year":"2022","journal-title":"Methods Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e00297","DOI":"10.1128\/mBio.00297-16","article-title":"Interaction between Simian Virus 40 Major Capsid Protein VP1 and Cell Surface Ganglioside GM1 Triggers Vacuole Formation","volume":"7","author":"Luo","year":"2016","journal-title":"mBio"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"972","DOI":"10.3390\/v2040972","article-title":"Lipid membranes in poxvirus replication","volume":"2","author":"Laliberte","year":"2010","journal-title":"Viruses"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1128\/JVI.79.3.1623-1634.2005","article-title":"Vaccinia virus penetration requires cholesterol and results in specific viral envelope proteins associated with lipid rafts","volume":"79","author":"Chung","year":"2005","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9301","DOI":"10.1128\/JVI.01545-13","article-title":"Primary human leukocyte subsets differentially express vaccinia virus receptors enriched in lipid rafts","volume":"87","author":"Byrd","year":"2013","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"658029","DOI":"10.3389\/fmolb.2021.658029","article-title":"Structural Basis of Glycan Recognition of Rotavirus","volume":"8","author":"Sun","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"15663","DOI":"10.1021\/bi961205g","article-title":"SPC3, a V3 loop-derived synthetic peptide inhibitor of HIV-1 infection, binds to cell surface glycosphingolipids","volume":"35","author":"Hammache","year":"1996","journal-title":"Biochemistry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1006\/bbrc.1998.8531","article-title":"Sequential interaction of CD4 and HIV-1 gp120 with a reconstituted membrane patch of ganglioside GM3: Implications for the role of glycolipids as potential HIV-1 fusion cofactors","volume":"246","author":"Hammache","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Jaafar, R., Boschi, C., Aherfi, S., Bancod, A., Le Bideau, M., Edouard, S., Colson, P., Chahinian, H., Raoult, D., and Yahi, N. (2021). High Individual Heterogeneity of Neutralizing Activities against the Original Strain and Nine Different Variants of SARS-CoV-2. Viruses, 13.","DOI":"10.3390\/v13112177"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s00705-021-05331-4","article-title":"Limited spread of a rare spike E484K-harboring SARS-CoV-2 in Marseille. France","volume":"167","author":"Colson","year":"2022","journal-title":"Arch. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"105960","DOI":"10.1016\/j.ijantimicag.2020.105960","article-title":"Structural and molecular modelling studies reveal a new mechanism of action of chloroquine and hydroxychloroquine against SARS-CoV-2 infection","volume":"55","author":"Fantini","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"106020","DOI":"10.1016\/j.ijantimicag.2020.106020","article-title":"Synergistic antiviral effect of hydroxychloroquine and azithromycin in combination against SARS-CoV-2: What molecular dynamics studies of virus-host interactions reveal","volume":"56","author":"Fantini","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1515\/bmc-2022-0006","article-title":"The epigenetic dimension of protein structure","volume":"13","author":"Azzaz","year":"2022","journal-title":"Biomol. Concepts"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Azzaz, F., Yahi, N., Chahinian, H., and Fantini, J. (2022). The Epigenetic Dimension of Protein Structure Is an Intrinsic Weakness of the AlphaFold Program. Biomolecules, 12.","DOI":"10.3390\/biom12101527"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1002\/jmv.27577","article-title":"The puzzling mutational landscape of the SARS-2-variant Omicron","volume":"94","author":"Fantini","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.jinf.2021.08.010","article-title":"Infection-enhancing anti-SARS-CoV-2 antibodies recognize both the original Wuhan\/D614G strain and Delta variants. A potential risk for mass vaccination?","volume":"83","author":"Yahi","year":"2021","journal-title":"J. Infect."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.1002\/jmv.27695","article-title":"First cases of infection with the 21L\/BA.2 Omicron variant in Marseille. France","volume":"94","author":"Colson","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3739","DOI":"10.1002\/jmv.27789","article-title":"Culture and identification of a \"Deltamicron\" SARS-CoV-2 in a three cases cluster in southern France","volume":"94","author":"Colson","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gu\u00e9rin, P., Yahi, N., Azzaz, F., Chahinian, H., Sabatier, J.M., and Fantini, J. (2022). Structural Dynamics of the SARS-CoV-2 Spike Protein: A 2-Year Retrospective Analysis of SARS-CoV-2 Variants (from Alpha to Omicron) Reveals an Early Divergence between Conserved and Variable Epitopes. Molecules, 27.","DOI":"10.3390\/molecules27123851"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1093\/glycob\/cwab032","article-title":"The role of cell surface sialic acids for SARS-CoV-2 infection","volume":"31","author":"Sun","year":"2021","journal-title":"Glycobiology"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kuchipudi, S.V., Nelli, R.K., Gontu, A., Satyakumar, R., Surendran Nair, M., and Subbiah, M. (2021). Sialic Acid Receptors: The Key to Solving the Enigma of Zoonotic Virus Spillover. Viruses, 13.","DOI":"10.3390\/v13020262"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.1021\/jm051197e","article-title":"MolDock: A new technique for high-accuracy molecular docking","volume":"49","author":"Thomsen","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5425","DOI":"10.1021\/bi00367a013","article-title":"New hydrophilicity scale derived from high-performance liquid chromatography peptide retention data: Correlation of predicted surface residues with antigenicity and X-ray-derived accessible sites","volume":"25","author":"Parker","year":"1986","journal-title":"Biochemistry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/BF01195768","article-title":"Prediction of chain flexibility in proteins","volume":"72","author":"Karplus","year":"1985","journal-title":"Naturwissenschaften"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1128\/jvi.55.3.836-839.1985","article-title":"Induction of hepatitis A virus-neutralizing antibody by a virus-specific synthetic peptide","volume":"55","author":"Emini","year":"1985","journal-title":"J. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/0165-2478(93)90072-A","article-title":"Correlation between the location of antigenic sites and the prediction of turns in proteins","volume":"36","author":"Pellequer","year":"1993","journal-title":"Immunol. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/0022-2836(78)90408-4","article-title":"Conformation of amino acid side-chains in proteins","volume":"125","author":"Janin","year":"1978","journal-title":"J. Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/0005-2795(80)90258-5","article-title":"Hydrophobic packing and spatial arrangement of amino acid residues in globular proteins","volume":"623","author":"Ponnuswamy","year":"1980","journal-title":"Biochim. Et Biophys. Acta (BBA)-Protein Struct."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/0014-5793(90)80535-Q","article-title":"A semi-empirical method for prediction of antigenic determinants on protein antigens","volume":"276","author":"Kolaskar","year":"1990","journal-title":"FEBS Lett."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Clifford, J., Hoeie, M.H., Nielsen, M., Deleuran, S., Peters, B., and Marcatili, P. (2022). BepiPred-3.0: Improved B-cell epitope prediction using protein language models. bioRxiv.","DOI":"10.1101\/2022.07.11.499418"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Saha, S., and Raghava, G.P.S. (2004). BcePred: Prediction of continuous B-cell epitopes in antigenic sequences using physico-chemical properties. International Conference on Artificial Immune Systems, Springer.","DOI":"10.1007\/978-3-540-30220-9_16"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"15983","DOI":"10.1038\/s41598-022-20397-z","article-title":"Novel multi epitope-based vaccine against monkeypox virus: Vaccinomic approach","volume":"12","author":"Shantier","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"El-Battari, A., Rodriguez, L., Chahinian, H., Del\u00e9zay, O., Fantini, J., Yahi, N., and Di Scala, C. (2021). Gene Therapy Strategy for Alzheimer\u2019s and Parkinson\u2019s Diseases Aimed at Preventing the Formation of Neurotoxic Oligomers in SH-SY5Y Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111550"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/978-1-59745-450-6_24","article-title":"Prediction of linear B-cell epitopes","volume":"524","author":"Reimer","year":"2009","journal-title":"Methods Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Galanis, K.A., Nastou, K.C., Papandreou, N.C., Petichakis, G.N., Pigis, D.G., and Iconomidou, V.A. (2021). Linear B-Cell Epitope Prediction for In Silico Vaccine Design: A Performance Review of Methods Available via Command-Line Interface. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063210"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s12272-022-01381-7","article-title":"mRNA vaccines: The most recent clinical applications of synthetic mRNA","volume":"45","author":"Kwon","year":"2022","journal-title":"Arch. Pharmacal Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3980","DOI":"10.1016\/j.cell.2022.09.022","article-title":"Primate hemorrhagic fever-causing arteriviruses are poised for spillover to humans","volume":"185","author":"Warren","year":"2022","journal-title":"Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.virol.2015.06.005","article-title":"Lipid rafts both in cellular membrane and viral envelope are critical for PRRSV efficient infection","volume":"484","author":"Yang","year":"2015","journal-title":"Virology"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/11\/2531\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:19:07Z","timestamp":1760145547000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/11\/2531"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,16]]},"references-count":53,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["v14112531"],"URL":"https:\/\/doi.org\/10.3390\/v14112531","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,16]]}}}