https://www.medrxiv.org/content/10.1101/2021.03.31.21254660v1 Skip to main content medRxiv * Home * About * Submit * ALERTS / RSS Search for this keyword [ ] [Search] Advanced Search Qualitatively distinct modes of Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike variants View ORCID ProfileSatoshi Ikegame, View ORCID ProfileMohammed N. A. Siddiquey, View ORCID ProfileChuan-Tien Hung, View ORCID Profile Griffin Haas, View ORCID ProfileLuca Brambilla, View ORCID Profile Kasopefoluwa Y. Oguntuyo, View ORCID ProfileShreyas Kowdle, Ariel Esteban Vilardo, View ORCID ProfileAlexis Edelstein, View ORCID ProfileClaudia Perandones, View ORCID ProfileJeremy P. Kamil, View ORCID ProfileBenhur Lee doi: https://doi.org/10.1101/2021.03.31.21254660 Satoshi Ikegame 1Department of Microbiology at the Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * ORCID record for Satoshi Ikegame Mohammed N. A. Siddiquey 2Department of Microbiology and Immunology, Louisiana State University Health Shreveport, Shreveport, LA 71103, USA * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * ORCID record for Mohammed N. A. Siddiquey Chuan-Tien Hung 1Department of Microbiology at the Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * ORCID record for Chuan-Tien Hung Griffin Haas 1Department of Microbiology at the Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * ORCID record for Griffin Haas Luca Brambilla 1Department of Microbiology at the Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * ORCID record for Luca Brambilla Kasopefoluwa Y. Oguntuyo 1Department of Microbiology at the Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * ORCID record for Kasopefoluwa Y. Oguntuyo Shreyas Kowdle 1Department of Microbiology at the Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * ORCID record for Shreyas Kowdle Ariel Esteban Vilardo 3National Administration of Laboratories and Health Institutes of Argentina (ANLIS) Dr. Carlos G. Malbran, Buenos Aires, Argentina * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Alexis Edelstein 3National Administration of Laboratories and Health Institutes of Argentina (ANLIS) Dr. Carlos G. Malbran, Buenos Aires, Argentina * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * ORCID record for Alexis Edelstein Claudia Perandones 3National Administration of Laboratories and Health Institutes of Argentina (ANLIS) Dr. Carlos G. Malbran, Buenos Aires, Argentina * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * ORCID record for Claudia Perandones Jeremy P. Kamil 2Department of Microbiology and Immunology, Louisiana State University Health Shreveport, Shreveport, LA 71103, USA * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * ORCID record for Jeremy P. Kamil Benhur Lee 1Department of Microbiology at the Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * ORCID record for Benhur Lee * For correspondence: benhur.lee@mssm.edu * Abstract * Full Text * Info/History * Metrics * Supplementary material * Data/Code * Preview PDF Loading ABSTRACT The novel pandemic betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected at least 120 million people since its identification as the cause of a December 2019 viral pneumonia outbreak in Wuhan, China. Despite the unprecedented pace of vaccine development, with six vaccines already in use worldwide, the emergence of SARS-CoV-2 'variants of concern' (VOC) across diverse geographic locales suggests herd immunity may fail to eliminate the virus. All three officially designated VOC carry Spike (S) polymorphisms thought to enable escape from neutralizing antibodies elicited during initial waves of the pandemic. Here, we characterize the biological consequences of the ensemble of S mutations present in VOC lineages B.1.1.7 (501Y.V1) and B.1.351 (501Y.V2). Using a replication-competent EGFP-reporter vesicular stomatitis virus (VSV) system, rcVSV-CoV2-S, which encodes S from SARS coronavirus 2 in place of VSV-G, and coupled with a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection, we determined that 8 out of 12 (75%) of serum samples from 12 recipients of the Russian Sputnik V Ad26 / Ad5 vaccine showed dose response curve slopes indicative of failure to neutralize rcVSV-CoV2-S: B.1.351. The same set of sera efficiently neutralized S from B.1.1.7 and showed only moderately reduced activity against S carrying the E484K substitution alone. Taken together, our data suggest that control of emergent SARS-CoV-2 variants may benefit from updated vaccines. Competing Interest Statement B.L. and K.Y.O. are named inventors on a patent filed by the Icahn School of Medicine for some of the materials used in this work. J.P.K. is a consultant for BioNTech (advisory panel on coronavirus variants). Funding Statement We acknowledge the following finding. K.Y.O. was supported by Viral-Host Pathogenesis Training Grant T32 AI07647 and additionally by a NRSA F31 AI154739. S.I. and C.-T.H. were supported by postdoctoral fellowships from CHOT-SG (Fukuoka University, Japan) and the Ministry of Science and Technology (MOST, Taiwan), respectively. B.L. acknowledges flexible funding support from NIH grants AI123449 and AI138921; a grant from the Department of Microbiology, Icahn School of Medicine at Mount Sinai; and the Ward-Coleman estate, which endowed the Ward-Coleman Chairs at the ISMMS. J.P.K. was supported by a COVID-19 Fast Grants award from Emergent Ventures, an initiative of the Mercatus Center at George Mason University, and by an intramural grant and other funding from the Office of the Vice Chancellor for Research at LSU Health Sciences Center Shreveport (J.P.K., M.N.A.S.). Processing costs recovered from multiple users of our standardized SARS-CoV-2 VSV pseudotyped particles provided additional support (BL). Work at ANLIS-MALBRAN (A.E.V., A.E., C.P.) was supported by the Ministry of Health (Ministerio de Salud), Argentina. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Human subjects research was conducted following the Declaration of Helsinki and related institutional and local regulations. Studies and serum collection relating to the Sputnik vaccine at ANLIS Dr. Carlos G. Malbran (NatIonal Administration Laboratories and Health Institutes - Carlos G. Malbran, Argentina) were approved by the Research Ethics Committee of its Unidad Operatlva Centro de Contencion Biologica (UOCCB) on February 9, 2021. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data Availability The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request, except for GISAID sequences, which are available from GISAID.org under the GISAID Data Use Agreement. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. View the discussion thread. Back to top PreviousNext Posted April 02, 2021. Download PDF Supplementary Material Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. 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