[{"intvolume":"         7","article_number":"145","article_type":"original","abstract":[{"text":"Replication-incompetent adenoviral vectors have been extensively used as a platform for vaccine design, with at least four anti-COVID-19 vaccines authorized to date. These vaccines elicit neutralizing antibody responses directed against SARS-CoV-2 Spike protein and confer significant level of protection against SARS-CoV-2 infection. Immunization with adenovirus-vectored vaccines is known to be accompanied by the production of anti-vector antibodies, which may translate into reduced efficacy of booster or repeated rounds of revaccination. Here, we used blood samples from patients who received an adenovirus-based Gam-COVID-Vac vaccine to address the question of whether anti-vector antibodies may influence the magnitude of SARS-CoV-2-specific humoral response after booster vaccination. We observed that rAd26-based prime vaccination with Gam-COVID-Vac induced the development of Ad26-neutralizing antibodies, which persisted in circulation for at least 9 months. Our analysis further indicates that high pre-boost Ad26 neutralizing antibody titers do not appear to affect the humoral immunogenicity of the Gam-COVID-Vac boost. The titers of anti-SARS-CoV-2 RBD IgGs and antibodies, which neutralized both the wild type and the circulating variants of concern of SARS-CoV-2 such as Delta and Omicron, were independent of the pre-boost levels of Ad26-neutralizing antibodies. Thus, our results support the development of repeated immunization schedule with adenovirus-based COVID-19 vaccines.","lang":"eng"}],"tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"volume":7,"title":"Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination","scopus_import":"1","department":[{"_id":"FyKo"}],"language":[{"iso":"eng"}],"date_created":"2023-01-12T12:02:54Z","citation":{"apa":"Byazrova, M. G., Astakhova, E. A., Minnegalieva, A., Sukhova, M. M., Mikhailov, A. A., Prilipov, A. G., … Filatov, A. V. (2022). Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination. <i>Npj Vaccines</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41541-022-00566-x\">https://doi.org/10.1038/s41541-022-00566-x</a>","ista":"Byazrova MG, Astakhova EA, Minnegalieva A, Sukhova MM, Mikhailov AA, Prilipov AG, Gorchakov AA, Filatov AV. 2022. Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination. npj Vaccines. 7, 145.","chicago":"Byazrova, Maria G., Ekaterina A. Astakhova, Aygul Minnegalieva, Maria M. Sukhova, Artem A. Mikhailov, Alexey G. Prilipov, Andrey A. Gorchakov, and Alexander V. Filatov. “Anti-Ad26 Humoral Immunity Does Not Compromise SARS-COV-2 Neutralizing Antibody Responses Following Gam-COVID-Vac Booster Vaccination.” <i>Npj Vaccines</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41541-022-00566-x\">https://doi.org/10.1038/s41541-022-00566-x</a>.","ieee":"M. G. Byazrova <i>et al.</i>, “Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination,” <i>npj Vaccines</i>, vol. 7. Springer Nature, 2022.","short":"M.G. Byazrova, E.A. Astakhova, A. Minnegalieva, M.M. Sukhova, A.A. Mikhailov, A.G. Prilipov, A.A. Gorchakov, A.V. Filatov, Npj Vaccines 7 (2022).","ama":"Byazrova MG, Astakhova EA, Minnegalieva A, et al. Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination. <i>npj Vaccines</i>. 2022;7. doi:<a href=\"https://doi.org/10.1038/s41541-022-00566-x\">10.1038/s41541-022-00566-x</a>","mla":"Byazrova, Maria G., et al. “Anti-Ad26 Humoral Immunity Does Not Compromise SARS-COV-2 Neutralizing Antibody Responses Following Gam-COVID-Vac Booster Vaccination.” <i>Npj Vaccines</i>, vol. 7, 145, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41541-022-00566-x\">10.1038/s41541-022-00566-x</a>."},"type":"journal_article","day":"15","doi":"10.1038/s41541-022-00566-x","quality_controlled":"1","oa_version":"Published Version","acknowledgement":"We thank Sergey Kulemzin, Grigory Efimov, Yuri Lebedin, Alexander Taranin and Rudolf Valenta for providing reagents. Figures were created with the help of BioRender.com. This work was supported by the Russian Science Foundation (Project 21-15-00286). Byazrova M.G. was supported by the RUDN University Strategic Academic Leadership Program.","author":[{"first_name":"Maria G.","full_name":"Byazrova, Maria G.","last_name":"Byazrova"},{"last_name":"Astakhova","full_name":"Astakhova, Ekaterina A.","first_name":"Ekaterina A."},{"first_name":"Aygul","full_name":"Minnegalieva, Aygul","last_name":"Minnegalieva","id":"87DF77F0-1D9A-11EA-B6AE-CE443DDC885E"},{"last_name":"Sukhova","first_name":"Maria M.","full_name":"Sukhova, Maria M."},{"last_name":"Mikhailov","first_name":"Artem A.","full_name":"Mikhailov, Artem A."},{"last_name":"Prilipov","first_name":"Alexey G.","full_name":"Prilipov, Alexey G."},{"full_name":"Gorchakov, Andrey A.","first_name":"Andrey A.","last_name":"Gorchakov"},{"last_name":"Filatov","first_name":"Alexander V.","full_name":"Filatov, Alexander V."}],"isi":1,"external_id":{"pmid":["36379998"],"isi":["000884278600004"]},"oa":1,"keyword":["Pharmacology (medical)","Infectious Diseases","Pharmacology","Immunology","SARS-COV-2","COVID"],"article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","date_published":"2022-11-15T00:00:00Z","ddc":["570"],"publication_identifier":{"issn":["2059-0105"]},"year":"2022","date_updated":"2023-08-04T08:52:40Z","publication_status":"published","_id":"12131","has_accepted_license":"1","publisher":"Springer Nature","file_date_updated":"2023-01-23T11:22:09Z","publication":"npj Vaccines","pmid":1,"month":"11","file":[{"checksum":"ddaac096381565b2b4b7dcc34cdbc4ee","file_size":1856046,"success":1,"relation":"main_file","content_type":"application/pdf","creator":"dernst","date_updated":"2023-01-23T11:22:09Z","access_level":"open_access","file_id":"12347","file_name":"2022_njpVaccines_Byazrova.pdf","date_created":"2023-01-23T11:22:09Z"}]},{"file_date_updated":"2023-01-30T09:22:26Z","publisher":"Frontiers Media","has_accepted_license":"1","file":[{"file_id":"12443","date_updated":"2023-01-30T09:22:26Z","creator":"dernst","access_level":"open_access","file_name":"2022_FrontiersImmunology_Dormeshkin.pdf","date_created":"2023-01-30T09:22:26Z","checksum":"f8f5d8110710033d0532e7e08bf9dad4","file_size":5695892,"success":1,"relation":"main_file","content_type":"application/pdf"}],"month":"09","publication":"Frontiers in Immunology","ddc":["570"],"status":"public","date_published":"2022-09-16T00:00:00Z","publication_identifier":{"issn":["1664-3224"]},"year":"2022","article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa":1,"keyword":["Immunology","Immunology and Allergy","COVID-19","SARS-CoV-2","synthetic library","RBD","neutralization nanobody","VHH"],"author":[{"last_name":"Dormeshkin","first_name":"Dmitri","full_name":"Dormeshkin, Dmitri"},{"last_name":"Shapira","full_name":"Shapira, Michail","first_name":"Michail"},{"full_name":"Dubovik, Simon","first_name":"Simon","last_name":"Dubovik"},{"id":"4968f7ad-eb97-11eb-a6c2-8ed382e8912c","last_name":"Kavaleuski","orcid":"0000-0003-2091-526X","full_name":"Kavaleuski, Anton","first_name":"Anton"},{"last_name":"Katsin","full_name":"Katsin, Mikalai","first_name":"Mikalai"},{"last_name":"Migas","first_name":"Alexandr","full_name":"Migas, Alexandr"},{"last_name":"Meleshko","full_name":"Meleshko, Alexander","first_name":"Alexander"},{"last_name":"Semyonov","first_name":"Sergei","full_name":"Semyonov, Sergei"}],"external_id":{"isi":["000862479100001"]},"isi":1,"acknowledgement":"The authors declare that this study received funding from Immunofusion. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.","_id":"12252","publication_status":"published","date_updated":"2023-08-04T09:49:24Z","type":"journal_article","day":"16","citation":{"apa":"Dormeshkin, D., Shapira, M., Dubovik, S., Kavaleuski, A., Katsin, M., Migas, A., … Semyonov, S. (2022). Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library. <i>Frontiers in Immunology</i>. Frontiers Media. <a href=\"https://doi.org/10.3389/fimmu.2022.965446\">https://doi.org/10.3389/fimmu.2022.965446</a>","ista":"Dormeshkin D, Shapira M, Dubovik S, Kavaleuski A, Katsin M, Migas A, Meleshko A, Semyonov S. 2022. Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library. Frontiers in Immunology. 13, 965446.","chicago":"Dormeshkin, Dmitri, Michail Shapira, Simon Dubovik, Anton Kavaleuski, Mikalai Katsin, Alexandr Migas, Alexander Meleshko, and Sergei Semyonov. “Isolation of an Escape-Resistant SARS-CoV-2 Neutralizing Nanobody from a Novel Synthetic Nanobody Library.” <i>Frontiers in Immunology</i>. Frontiers Media, 2022. <a href=\"https://doi.org/10.3389/fimmu.2022.965446\">https://doi.org/10.3389/fimmu.2022.965446</a>.","ieee":"D. Dormeshkin <i>et al.</i>, “Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library,” <i>Frontiers in Immunology</i>, vol. 13. Frontiers Media, 2022.","ama":"Dormeshkin D, Shapira M, Dubovik S, et al. Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library. <i>Frontiers in Immunology</i>. 2022;13. doi:<a href=\"https://doi.org/10.3389/fimmu.2022.965446\">10.3389/fimmu.2022.965446</a>","short":"D. Dormeshkin, M. Shapira, S. Dubovik, A. Kavaleuski, M. Katsin, A. Migas, A. Meleshko, S. Semyonov, Frontiers in Immunology 13 (2022).","mla":"Dormeshkin, Dmitri, et al. “Isolation of an Escape-Resistant SARS-CoV-2 Neutralizing Nanobody from a Novel Synthetic Nanobody Library.” <i>Frontiers in Immunology</i>, vol. 13, 965446, Frontiers Media, 2022, doi:<a href=\"https://doi.org/10.3389/fimmu.2022.965446\">10.3389/fimmu.2022.965446</a>."},"oa_version":"Published Version","doi":"10.3389/fimmu.2022.965446","quality_controlled":"1","abstract":[{"lang":"eng","text":"The COVID−19 pandemic not only resulted in a global crisis, but also accelerated vaccine development and antibody discovery. Herein we report a synthetic humanized VHH library development pipeline for nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD) isolation. Trinucleotide-based randomization of CDRs by Kunkel mutagenesis with the subsequent rolling-cycle amplification resulted in more than 10<jats:sup>11</jats:sup> diverse phage display library in a manageable for a single person number of electroporation reactions. We identified a number of nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD) by screening a novel synthetic humanized antibody library. In order to explore the most robust and fast method for affinity improvement, we performed affinity maturation by CDR1 and CDR2 shuffling and avidity engineering by multivalent trimeric VHH fusion protein construction. As a result, H7-Fc and G12x3-Fc binders were developed with the affinities in nM and pM range respectively. Importantly, these affinities are weakly influenced by most of SARS-CoV-2 VoC mutations and they retain moderate binding to BA.4\\5. The plaque reduction neutralization test (PRNT) resulted in IC50 = 100 ng\\ml and 9.6 ng\\ml for H7-Fc and G12x3-Fc antibodies, respectively, for the emerging Omicron BA.1 variant. Therefore, these VHH could expand the present landscape of SARS-CoV-2 neutralization binders with the therapeutic potential for present and future SARS-CoV-2 variants."}],"tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"volume":13,"intvolume":"        13","article_type":"original","article_number":"965446","language":[{"iso":"eng"}],"date_created":"2023-01-16T09:56:57Z","department":[{"_id":"LeSa"}],"title":"Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library","scopus_import":"1"}]