{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:57:45Z","timestamp":1760147865986,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Viravaxx AG","award":["075-15-2021-632 (14.W03.31.0024)","21-15-00286"],"award-info":[{"award-number":["075-15-2021-632 (14.W03.31.0024)","21-15-00286"]}]},{"name":"Megagrant of the Government of the Russian Federation","award":["075-15-2021-632 (14.W03.31.0024)","21-15-00286"],"award-info":[{"award-number":["075-15-2021-632 (14.W03.31.0024)","21-15-00286"]}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["075-15-2021-632 (14.W03.31.0024)","21-15-00286"],"award-info":[{"award-number":["075-15-2021-632 (14.W03.31.0024)","21-15-00286"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"name":"RUDN University Strategic Academic Leadership Program","award":["075-15-2021-632 (14.W03.31.0024)","21-15-00286"],"award-info":[{"award-number":["075-15-2021-632 (14.W03.31.0024)","21-15-00286"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Millions of people have been vaccinated with Gam-COVID-Vac but fine specificities of induced antibodies have not been fully studied. Plasma from 12 na\u00efve and 10 coronavirus disease 2019 (COVID-19) convalescent subjects was obtained before and after two immunizations with Gam-COVID-Vac. Antibody reactivity in the plasma samples (n = 44) was studied on a panel of micro-arrayed recombinant folded and unfolded severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins and 46 peptides spanning the spike protein (S) and by immunoglobulin G (IgG) subclass enzyme-linked immunosorbent assay (ELISA). The ability of Gam-COVID-Vac-induced antibodies to inhibit binding of the receptor-binding domain (RBD) to its receptor angiotensin converting enzyme 2 (ACE2) was investigated in a molecular interaction assay (MIA). The virus-neutralizing capacity of antibodies was studied by the pseudo-typed virus neutralization test (pVNT) for Wuhan-Hu-1 and Omicron. We found that Gam-COVID-Vac vaccination induced significant increases of IgG1 but not of other IgG subclasses against folded S, spike protein subunit 1 (S1), spike protein subunit 2 (S2), and RBD in a comparable manner in na\u00efve and convalescent subjects. Virus neutralization was highly correlated with vaccination-induced antibodies specific for folded RBD and a novel peptide (i.e., peptide 12). Peptide 12 was located close to RBD in the N-terminal part of S1 and may potentially be involved in the transition of the pre- to post-fusion conformation of the spike protein. In summary, Gam-COVID-Vac vaccination induced S-specific IgG1 antibodies in naive and convalescent subjects in a comparable manner. Besides the antibodies specific for RBD, the antibodies induced against a peptide close to the N-terminus of RBD were also associated with virus-neutralization.<\/jats:p>","DOI":"10.3390\/ijms24065104","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T02:30:23Z","timestamp":1678242623000},"page":"5104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dissection of Antibody Responses of Gam-COVID-Vac-Vaccinated Subjects Suggests Involvement of Epitopes Outside RBD in SARS-CoV-2 Neutralization"],"prefix":"10.3390","volume":"24","author":[{"given":"Maria","family":"Byazrova","sequence":"first","affiliation":[{"name":"National Research Center\u2014Institute of Immunology FMBA of Russia, 115478 Moscow, Russia"},{"name":"Department of Immunology, Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia"},{"name":"Department of Immunology, Peoples\u2019 Friendship University of Russia (RUDN University) of Ministry of Science and Higher Education of the Russian Federation, 117198 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6724-8543","authenticated-orcid":false,"given":"Pia","family":"Gattinger","sequence":"additional","affiliation":[{"name":"Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina","family":"Astakhova","sequence":"additional","affiliation":[{"name":"National Research Center\u2014Institute of Immunology FMBA of Russia, 115478 Moscow, Russia"},{"name":"Department of Immunology, Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerhard","family":"Hofer","sequence":"additional","affiliation":[{"name":"Department of Materials and Environmental Chemistry, University of Stockholm, 106 91 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Musa","family":"Khaitov","sequence":"additional","affiliation":[{"name":"National Research Center\u2014Institute of Immunology FMBA of Russia, 115478 Moscow, Russia"},{"name":"Department of Immunology, Pirogov Russian National Research Medical University, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6460-9427","authenticated-orcid":false,"given":"Alexander","family":"Filatov","sequence":"additional","affiliation":[{"name":"National Research Center\u2014Institute of Immunology FMBA of Russia, 115478 Moscow, Russia"},{"name":"Department of Immunology, Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudolf","family":"Valenta","sequence":"additional","affiliation":[{"name":"National Research Center\u2014Institute of Immunology FMBA of Russia, 115478 Moscow, Russia"},{"name":"Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Clinical Immunology and Allergy, Sechenov First Moscow State Medical University, 119435 Moscow, Russia"},{"name":"Karl Landsteiner University of Health Sciences, 3500 Krems, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1111\/all.14714","article-title":"SARS-CoV-2 candidate vaccines\u2014Composition, mechanisms of action and stages of clinical development","volume":"76","author":"Sokolowska","year":"2021","journal-title":"Allergy"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sharma, A., Ahmad, F.I., and Lal, S.K. (2021). COVID-19: A Review on the Novel Coronavirus Disease Evolution, Transmission, Detection, Control and Prevention. Viruses, 13.","DOI":"10.3390\/v13020202"},{"key":"ref_3","first-page":"1469","article-title":"Review-Insights into Off-Label therapeutic strategies against mild and severe COVID-19 infection","volume":"34","author":"Arshad","year":"2021","journal-title":"Pak. J. Pharm. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1002\/ptr.6787","article-title":"COVID-19: Phylogenetic approaches may help in finding resources for natural cure","volume":"34","author":"Zaman","year":"2020","journal-title":"Phytother. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.3390\/covid2080080","article-title":"SARS-CoV-2 Intermittent Virulence as a Result of Natural Selection","volume":"2","author":"Redwan","year":"2022","journal-title":"COVID"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/S0140-6736(20)31866-3","article-title":"Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: Two open, non-randomised phase 1\/2 studies from Russia","volume":"396","author":"Logunov","year":"2020","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/S0140-6736(20)31604-4","article-title":"Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: A preliminary report of a phase 1\/2, single-blind, randomised controlled trial","volume":"396","author":"Folegatti","year":"2020","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S0140-6736(21)00234-8","article-title":"Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: An interim analysis of a randomised controlled phase 3 trial in Russia","volume":"397","author":"Logunov","year":"2021","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41580-021-00418-x","article-title":"Mechanisms of SARS-CoV-2 entry into cells","volume":"23","author":"Jackson","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/s41541-021-00369-6","article-title":"Distinguishing features of current COVID-19 vaccines: Knowns and unknowns of antigen presentation and modes of action","volume":"6","author":"Heinz","year":"2021","journal-title":"NPJ Vaccines"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lim, H.X., Masomian, M., Khalid, K., Kumar, A.U., MacAry, P.A., and Poh, C.L. (2022). Identification of B-Cell Epitopes for Eliciting Neutralizing Antibodies against the SARS-CoV-2 Spike Protein through Bioinformatics and Monoclonal Antibody Targeting. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084341"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"899477","DOI":"10.3389\/fddsv.2022.899477","article-title":"Peptide-Based Strategies Against SARS-CoV-2 Attack: An Updated In Silico Perspective","volume":"2","author":"Moroy","year":"2022","journal-title":"Front. Drug. Discov."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/all.15066","article-title":"Neutralization of SARS-CoV-2 requires antibodies against conformational receptor-binding domain epitopes","volume":"77","author":"Gattinger","year":"2022","journal-title":"Allergy"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"647934","DOI":"10.3389\/fimmu.2021.647934","article-title":"A Structural Landscape of Neutralizing Antibodies Against SARS-CoV-2 Receptor Binding Domain","volume":"12","author":"Niu","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"766821","DOI":"10.3389\/fimmu.2021.766821","article-title":"A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants","volume":"12","author":"Shan","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"928279","DOI":"10.3389\/fcimb.2022.928279","article-title":"Broadly Neutralizing Antibodies to SARS-CoV-2 Provide Novel Insights Into the Neutralization of Variants and Other Human Coronaviruses","volume":"12","author":"Bajpai","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"613045","DOI":"10.3389\/fimmu.2021.613045","article-title":"Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Based Novel Epitopes Induce Potent Immune Responses in vivo and Inhibit Viral Replication in vitro","volume":"12","author":"Vishwakarma","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e73490","DOI":"10.7554\/eLife.73490","article-title":"Comprehensive characterization of the antibody responses to SARS-CoV-2 Spike protein finds additional vaccine-induced epitopes beyond those for mild infection","volume":"11","author":"Garrett","year":"2022","journal-title":"eLife"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"938378","DOI":"10.3389\/fimmu.2022.938378","article-title":"Protective antigenic epitopes revealed by immunosignatures after three doses of inactivated SARS-CoV-2 vaccine","volume":"13","author":"Peng","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"833085","DOI":"10.3389\/fimmu.2022.833085","article-title":"Humoral Immune Response Diversity to Different COVID-19 Vaccines: Implications for the \u201cGreen Pass\u201d Policy","volume":"13","author":"Polvere","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"100241","DOI":"10.1016\/j.lanepe.2021.100241","article-title":"An open, non-randomised, phase 1\/2 trial on the safety, tolerability, and immunogenicity of single-dose vaccine \u201cSputnik Light\u201d for prevention of coronavirus infection in healthy adults","volume":"11","author":"Tukhvatulin","year":"2021","journal-title":"Lancet Reg. Health Eur."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"101126","DOI":"10.1016\/j.eclinm.2021.101126","article-title":"Effectiveness of the first component of Gam-COVID-Vac (Sputnik V) on reduction of SARS-CoV-2 confirmed infections, hospitalisations and mortality in patients aged 60\u201379: A retrospective cohort study in Argentina","volume":"40","author":"Gonzalez","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Gushchin, V.A., Dolzhikova, I.V., and Shchetinin, A.M. (2021). Neutralizing Activity of Sera from Sputnik V-Vaccinated People against Variants of Concern (VOC: B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3) and Moscow Endemic SARS-CoV-2 Variants. Vaccines, 9.","DOI":"10.3390\/vaccines9070779"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.cmi.2021.11.011","article-title":"Nationwide effectiveness of five SARS-CoV-2 vaccines in Hungary-the HUN-VE study","volume":"28","author":"Voko","year":"2022","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1038\/s41598-022-05788-6","article-title":"Immune responses following the first dose of the Sputnik V (Gam-COVID-Vac)","volume":"12","author":"Jeewandara","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4598","DOI":"10.1038\/s41467-021-24909-9","article-title":"Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants","volume":"12","author":"Ikegame","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"101360","DOI":"10.1016\/j.eclinm.2022.101360","article-title":"Sputnik V protection from COVID-19 in people living with HIV under antiretroviral therapy","volume":"46","author":"Gushchin","year":"2022","journal-title":"EClinicalMedicine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3627","DOI":"10.1111\/all.14908","article-title":"The role of allergen-specific IgE, IgG and IgA in allergic disease","volume":"76","author":"Shamji","year":"2021","journal-title":"Allergy"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.ebiom.2019.11.006","article-title":"Two years of treatment with the recombinant grass pollen allergy vaccine BM32 induces a continuously increasing allergen-specific IgG4 response","volume":"50","author":"Weber","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1111\/all.13138","article-title":"Biomarkers for monitoring clinical efficacy of allergen immunotherapy for allergic rhinoconjunctivitis and allergic asthma: An EAACI Position Paper","volume":"72","author":"Shamji","year":"2017","journal-title":"Allergy"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1126\/science.abe3354","article-title":"Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms","volume":"370","author":"Tortorici","year":"2020","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Cia, G., Pucci, F., and Rooman, M. (2022). Analysis of the Neutralizing Activity of Antibodies Targeting Open or Closed SARS-CoV-2 Spike Protein Conformations. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23042078"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"111220","DOI":"10.1016\/j.celrep.2022.111220","article-title":"SARS-CoV-2 spike N-terminal domain modulates TMPRSS2-dependent viral entry and fusogenicity","volume":"40","author":"Meng","year":"2022","journal-title":"Cell Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1111\/j.1365-2222.2011.03798.x","article-title":"Molecular characterization of Der p 10: A diagnostic marker for broad sensitization in house dust mite allergy","volume":"41","author":"Resch","year":"2011","journal-title":"Clin. Exp. Allergy"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e1245","DOI":"10.1002\/cti2.1245","article-title":"Pattern of circulating SARS-CoV-2-specific antibody-secreting and memory B-cell generation in patients with acute COVID-19","volume":"10","author":"Byazrova","year":"2021","journal-title":"Clin. Transl. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1111\/all.14523","article-title":"Antibodies in serum of convalescent patients following mild COVID-19 do not always prevent virus-receptor binding","volume":"76","author":"Gattinger","year":"2021","journal-title":"Allergy"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1111\/all.15264","article-title":"Omicron: A SARS-CoV-2 variant of real concern","volume":"77","author":"Gattinger","year":"2022","journal-title":"Allergy"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5352","DOI":"10.3390\/ijms24065352","article-title":"Importance, Applications and Features of Assays Measuring SARS-CoV-2 Neutralizing Antibodies","volume":"24","author":"Gattinger","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2431","DOI":"10.1111\/all.15305","article-title":"Vaccine based on folded receptor binding domain-PreS fusion protein with potential to induce sterilizing immunity to SARS-CoV-2 variants","volume":"77","author":"Gattinger","year":"2022","journal-title":"Allergy"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5104\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:50:00Z","timestamp":1760122200000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,7]]},"references-count":39,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24065104"],"URL":"https:\/\/doi.org\/10.3390\/ijms24065104","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2023,3,7]]}}}