{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T22:25:22Z","timestamp":1775687122727,"version":"3.50.1"},"reference-count":28,"publisher":"Central Research Institute for Epidemiology","issue":"3","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["virusjour.crie.ru"],"crossmark-restriction":false},"short-container-title":["Problems of Virology"],"abstract":"<jats:p>Introduction. Norovirus (NoV) is one of the main causes of acute gastroenteritis. Currently, there is no vaccine to prevent norovirus infection. Vaccines under development are based on the capsid protein VP1, which is capable of forming virus-like particles.\r\nThe aim of the work was to analyze the immunogenic properties of the recombinant VP1 protein of NoV GII.4.\r\nMaterials and methods. In the blood serum of animals immunized with the recombinant VP1 protein obtained by the authors, titers and avidity of total antibodies and IgM antibodies against NoV VP1 were determined using enzyme immunoassay. The ability of the obtained antibodies to interact with NoV of different genotypes was assessed using immunoelectron microscopy.\r\nResults. The recombinant VP1 protein induced high titer antibody production in animals. Total antibodies against VP1 had a high avidity, reaching 100%, which suggests that they have viral neutralizing activity. IgM antibodies had low avidity. Immunoelectron microscopy showed that IgG antibodies against VP1 protein of genotype GII.4 interact with wild-type NoV of genotype GII.7 and GII.17.\r\nConclusion. The obtained recombinant protein induces a sufficiently strong immune response with the formation of high avidity polyclonal cross-reacting antibodies, which allows us to consider it as an antigen component of a NoV vaccine candidate.<\/jats:p>","DOI":"10.36233\/0507-4088-316","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T13:27:14Z","timestamp":1753104434000},"page":"282-290","update-policy":"https:\/\/doi.org\/10.36233\/0372-9311-crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Recombinant VP1 protein of norovirus GII.4 (Caliciviridae: &lt;i&gt;Norovirus&lt;\/i&gt;) is capable to induse the production of cross-reacting antibodies"],"prefix":"10.36233","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5905-5722","authenticated-orcid":false,"given":"Vladislav A.","family":"Lapin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7049-6935","authenticated-orcid":false,"given":"Dmitry V.","family":"Novikov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1033-7347","authenticated-orcid":false,"given":"Alexander Yu.","family":"Kashnikov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7679-8029","authenticated-orcid":false,"given":"Natalia V.","family":"Epifanova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3710-6648","authenticated-orcid":false,"given":"Nadezhda A.","family":"Novikova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9742-7646","authenticated-orcid":false,"given":"Ekaterina V.","family":"Mokhonova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2441-6874","authenticated-orcid":false,"given":"Dmitry A.","family":"Melentev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2811-6844","authenticated-orcid":false,"given":"Maria I.","family":"Tsyganova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7663-6924","authenticated-orcid":false,"given":"Dmitry E.","family":"Zaitsev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2449-7213","authenticated-orcid":false,"given":"Viktor V.","family":"Novikov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"22004","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Sergevnin V.I. Modern trends in long-term dynamics of the acute intestinal infections incidence of bacterial and viral etiology. Epidemiologiya i vaktsinoprofilaktika. 2020; 19(4): 14\u20139. https:\/\/doi.org\/10.31631\/2073-3046-2020-19-4-14-19 https:\/\/elibrary.ru\/zejihk (in Russian)","DOI":"10.31631\/2073-3046-2020-19-4-14-19"},{"key":"ref2","unstructured":"Hall A.J., Wikswo M.E., Pringle K. Vital signs: foodborne norovirus outbreaks \u2013 United States, 2009\u20132012. MMWR Morb. Mortal Wkly Rep. 2014; 63(22): 491\u20135."},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Netzler N.E., Enosi Tuipulotu D., White P.A. Norovirus antivirals: Where are we now? Med. Res. Rev. 2019; 39(3): 860\u201386. https:\/\/doi.org\/10.1002\/med.21545","DOI":"10.1002\/med.21545"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Hasso-Agopsowicz M., Hwang A., Hollm-Delgado M.G., Umbelino-Walker I., Karron R.A., Rao R., et al. Identifying WHO global priority endemic pathogens for vaccine research and development using multi-criteria decision analysis. EBioMedicine. 2024; 110: 105424. https:\/\/doi.org\/10.1016\/j.ebiom.2024.105424","DOI":"10.1016\/j.ebiom.2024.105424"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Prasad B.V., Hardy M.E., Dokland T., Bella J., Rossmann M.G., Estes M.K. X-ray crystallographic structure of the Norwalk virus capsid. Science. 1999; 286(5438): 287\u201390. https:\/\/doi.org\/10.1126\/science.286.5438.287","DOI":"10.1126\/science.286.5438.287"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Chhabra P., de Graaf M., Parra G.I., Chan M.C., Green K., Martella V., et al. Updated classification of norovirus genogroups and genotypes. J. Gen. Virol. 2019; 100(10): 1393\u2013406. https:\/\/doi.org\/10.1099\/jgv.0.001318","DOI":"10.1099\/jgv.0.001318"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Tan M., Jiang X. The p domain of norovirus capsid protein forms a subviral particle that binds to histo-blood group antigen receptors. J Virol. 2005; 79(22): 14017\u201330. https:\/\/doi.org\/10.1128\/JVI.79.22.14017-14030.2005","DOI":"10.1128\/JVI.79.22.14017-14030.2005"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Bertolotti-Ciarlet A., White L.J., Chen R., Prasad B.V., Estes M.K. Structural requirements for the assembly of Norwalk virus-like particles. J. Virol. 2002; 76(8): 4044\u201355. https:\/\/doi.org\/10.1128\/JVI.76.8.4044-4055.2002","DOI":"10.1128\/JVI.76.8.4044-4055.2002"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Fang H., Tan M., Xia M., Wang L., Jiang X. Norovirus P particle efficiently elicits innate, humoral and cellular immunity. PLoS One. 2013; 8(5): e63269. https:\/\/doi.org\/10.1371\/journal.pone.0063269","DOI":"10.1371\/journal.pone.0063269"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Mohsen M.O., Gomes A.C., Vogel M., Bachmann M.F. Interaction of viral capsid-derived virus-like particles with the innate immune system. Vaccines (Basel). 2018; 6(3): 37. https:\/\/doi.org\/10.3390\/vaccines6030037","DOI":"10.3390\/vaccines6030037"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Cates J.E., Vinj\u00e9 J., Parashar U., Hall A.J. Recent advances in human norovirus research and implications for candidate vaccines. Expert. Rev. Vaccines. 2020; 19(6): 539\u201348. https:\/\/doi.org\/10.1080\/14760584.2020.1777860","DOI":"10.1080\/14760584.2020.1777860"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Lapin V.A., Novikov D.V., Mokhonova E.V., Melentyev D.A., Tsyganova M.I., Zaitsev D.E., et al. Production of recombinant norovirus VP1 protein and its antigenic and immunogenic properties. Zhurnal mikrobiologii, epidemiologii i immunobiologii. 2024; 101(5): 661\u20137. 2024; 101(5): 661\u20137. https:\/\/doi.org\/10.36233\/0372-9311-552 https:\/\/elibrary.ru\/ubmktf (in Russian)","DOI":"10.36233\/0372-9311-552"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Parra G.I., Azure J., Fischer R., Bok K., Sandoval-Jaime C., Sosnovtsev S.V., et al. Identification of a broadly cross-reactive epitope in the inner shell of the norovirus capsid. PLoS One. 2013; 8(6): e67592. https:\/\/doi.org\/10.1371\/journal.pone.0067592","DOI":"10.1371\/journal.pone.0067592"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Li X., Zhou R., Tian X., Li H., Zhou Z. Characterization of a cross-reactive monoclonal antibody against Norovirus genogroups I, II, III and V. Virus Res. 2010; 151(2): 142\u20137. https:\/\/doi.org\/10.1016\/j.virusres.2010.04.005","DOI":"10.1016\/j.virusres.2010.04.005"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Parra G.I., Abente E.J., Sandoval-Jaime C., Sosnovtsev S.V., Bok K., Green K.Y. Multiple antigenic sites are involved in blocking the interaction of GII.4 Norovirus capsid with ABH histo-blood group antigens. J. Virol. 2012; 86(13): 7414\u201326. https:\/\/doi.org\/10.1128\/JVI.06729-11","DOI":"10.1128\/JVI.06729-11"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Parker T.D., Kitamoto N., Tanaka T., Hutson A.M., Estes M.K. Identification of Genogroup I and Genogroup II broadly reactive epitopes on the norovirus capsid. J. Virol. 2005; 79(11): 7402\u20139. https:\/\/doi.org\/10.1128\/JVI.79.11.7402-7409.2005","DOI":"10.1128\/JVI.79.12.7402-7409.2005"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Shiota T., Okame M., Takanashi S., Khamrin P., Takagi M., Satou K., et al. Characterization of a broadly reactive monoclonal antibody against norovirus genogroups I and II: recognition of a novel conformational epitope. J. Virol. 2007; 81(21): 12298\u2013306. https:\/\/doi.org\/10.1128\/JVI.01196-07","DOI":"10.1128\/JVI.00891-07"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Li X., Zhou R., Wang Y., Sheng H., Tian X., Li H., et al. Identification and characterization of a native epitope common to norovirus strains GII\/4, GII\/7 and GII\/8. Virus Res. 2009; 140(1-2): 188\u201393. https:\/\/doi.org\/10.1016\/j.virusres.2009.01.015","DOI":"10.1016\/j.virusres.2008.12.004"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Yoda T., Terano Y., Suzuki Y., Yamazaki K., Oishi I., Utagawa E., et al. Characterization of monoclonal antibodies generated against Norwalk virus GII capsid protein expressed in Escherichia coli. Microbiol. Immunol. 2000; 44(11): 905\u201314. https:\/\/doi.org\/10.1111\/j.1348-0421.2000.tb02579.x","DOI":"10.1111\/j.1348-0421.2000.tb02582.x"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Almanza H., Cubillos C., Angulo I., Mateos F., Cast\u00f3n J.R., van der Poel W.H., et al. Self-assembly of the recombinant capsid protein of a swine norovirus into virus-like particles and evaluation of monoclonal antibodies cross-reactive with a human strain from genogroup II. J. Clin. Microbiol. 2008; 46(12): 3971\u20139. https:\/\/doi.org\/10.1128\/jcm.01204-08","DOI":"10.1128\/JCM.01204-08"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Lindesmith L.C., McDaniel J.R., Changela A., Verardi R., Kerr S.A., Costantini V., et al. Sera antibody repertoire analyses reveal mechanisms of broad and pandemic strain neutralizing responses after human norovirus vaccination. Immunity. 2019; 50(6): 1530\u201341. https:\/\/doi.org\/10.1016\/j.immuni.2019.05.007","DOI":"10.1016\/j.immuni.2019.05.007"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Hansman G.S., Taylor D.W., McLellan J.S., Smith T.J., Georgiev I., Tame J.R., et al. Structural basis for broad detection of genogroup II noroviruses by a monoclonal antibody that binds to a site occluded in the viral particle. J. Virol. 2012; 86(7): 3635\u201346. https:\/\/doi.org\/10.1128\/JVI.06868-11","DOI":"10.1128\/JVI.06868-11"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Ford-Siltz L.A., Tohma K., Parra G.I. Understanding the relationship between norovirus diversity and immunity. Gut Microbes. 2021; 13(1): 1\u201313. https:\/\/doi.org\/10.1080\/19490976.2021.1900994","DOI":"10.1080\/19490976.2021.1900994"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Winder N., Gohar S., Muthana M. Norovirus: An overview of virology and preventative measures. Viruses. 2022; 14(12): 2811. https:\/\/doi.org\/10.3390\/v14122811","DOI":"10.3390\/v14122811"},{"key":"ref25","unstructured":"Zharova A.M.D., Talayev V.Yu., Perenkov A.D., Zaichenko I.Ye., Svetlova M.V., Babaykina O.N., et al. In silico analysis of the antigenic properties of norovirus GII.4 Sydney [P16] VP1 protein. Opera Med. Physiol. 2023; 10(3): 140\u201351. https:\/\/doi.org\/10.24412\/2500-2295-2023-3-140-151"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Alvarado G., Salmen W., Ettayebi K., Hu L., Sankaran B., Estes M.K., et al. Broadly cross-reactive human antibodies that inhibit genogroup I and II noroviruses. Nat. Commun. 2021; 12(1): 4320. https:\/\/doi.org\/10.1038\/s41467-021-24649-w","DOI":"10.1038\/s41467-021-24649-w"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Park J., Lindesmith L.C., Olia A.S., Costantini V.P., Brewer-Jensen P.D., Mallory M.L., et al. Broadly neutralizing antibodies targeting pandemic GII.4 variants or seven GII genotypes of human norovirus. Sci. Transl. Med. 2025; 17(788): eads8214. https:\/\/doi.org\/10.1126\/scitranslmed.ads8214","DOI":"10.1126\/scitranslmed.ads8214"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Lindesmith L.C., McDaniel J.R., Changela A., Verardi R., Kerr S.A., Costantini V., et al. Sera antibody repertoire analyses reveal mechanisms of broad and pandemic strain neutralizing responses after human norovirus vaccination. Immunity. 2019; 50(6): 1530\u201341.e8. https:\/\/doi.org\/10.1016\/j.immuni.2019.05.007","DOI":"10.1016\/j.immuni.2019.05.007"}],"container-title":["Problems of Virology"],"original-title":[],"link":[{"URL":"https:\/\/virusjour.crie.ru\/jour\/article\/viewFile\/16753\/1000","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/virusjour.crie.ru\/jour\/article\/viewFile\/16753\/1000","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T13:29:15Z","timestamp":1753104555000},"score":1,"resource":{"primary":{"URL":"https:\/\/virusjour.crie.ru\/jour\/article\/view\/16753"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,21]]},"references-count":28,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,7,21]]}},"URL":"https:\/\/doi.org\/10.36233\/0507-4088-316","relation":{},"ISSN":["2411-2097","0507-4088"],"issn-type":[{"value":"2411-2097","type":"electronic"},{"value":"0507-4088","type":"print"}],"subject":[],"published":{"date-parts":[[2025,7,21]]}}}