{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T06:43:42Z","timestamp":1762325022379,"version":"3.37.3"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,22]],"date-time":"2021-05-22T00:00:00Z","timestamp":1621641600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,22]],"date-time":"2021-05-22T00:00:00Z","timestamp":1621641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM063075"],"award-info":[{"award-number":["R01GM063075"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["R01AT005076"],"award-info":[{"award-number":["R01AT005076"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Med"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A SARS-like coronavirus 2 (SARS-CoV-2) has caused a pandemic Coronavirus Disease 2019 (COVID-19) that killed more than 3.3 million people worldwide. Like the SARS-CoV, SARS-CoV-2 also employs a receptor-binding motif (RBM) of its spike protein to bind a host receptor, the angiotensin-converting enzyme 2 (ACE2), to gain entry. Currently, several mRNA or adenoviral vaccines encoding for the spike protein of SARS-CoV-2 are being used to boost antibodies capable of\u00a0inhibiting spike-ACE2 interaction and viral entry. However, recent evidence has also suggested an anti-inflammatory effect of spike-reactive antibodies, suggesting that some SARS-CoV-2 spike-based vaccines may elicit protective antibodies capable of inhibiting GM-CSF production and COVID-19 progression.<\/jats:p>","DOI":"10.1186\/s10020-021-00313-3","type":"journal-article","created":{"date-parts":[[2021,5,22]],"date-time":"2021-05-22T13:02:53Z","timestamp":1621688573000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Possible inhibition of GM-CSF production by SARS-CoV-2 spike-based vaccines"],"prefix":"10.1186","volume":"27","author":[{"given":"Jianhua","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin J.","family":"Tracey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0211-9000","authenticated-orcid":false,"given":"Haichao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,5,22]]},"reference":[{"issue":"4","key":"313_CR1","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.immuni.2020.03.007","volume":"52","author":"F Amanat","year":"2020","unstructured":"Amanat F, Krammer F. SARS-CoV-2 vaccines: status report. Immunity. 2020;52(4):583\u20139.","journal-title":"Immunity"},{"issue":"1","key":"313_CR2","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1186\/s12967-020-02646-9","volume":"18","author":"M Blot","year":"2020","unstructured":"Blot M, Bour JB, Quenot JP, Bourredjem A, Nguyen M, Guy J, et al. The dysregulated innate immune response in severe COVID-19 pneumonia that could drive poorer outcome. J Transl Med. 2020;18(1):457\u201302646.","journal-title":"J Transl Med"},{"issue":"8","key":"313_CR3","doi-asserted-by":"publisher","first-page":"e465","DOI":"10.1016\/S2665-9913(20)30170-3","volume":"2","author":"LG De","year":"2020","unstructured":"De LG, Cavalli G, Campochiaro C, Della-Torre E, Angelillo P, Tomelleri A, et al. GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study. Lancet Rheumatol. 2020;2(8):e465\u201373.","journal-title":"Lancet Rheumatol"},{"key":"313_CR4","doi-asserted-by":"publisher","first-page":"e13001","DOI":"10.15252\/emmm.202013001","volume":"19","author":"L Gibellini","year":"2020","unstructured":"Gibellini L, De BS, Paolini A, Borella R, Boraldi F, Mattioli M, et al. Altered bioenergetics and mitochondrial dysfunction of monocytes in patients with COVID-19 pneumonia. EMBO Mol Med. 2020;19:e13001. https:\/\/doi.org\/10.15252\/emmm.202013001.","journal-title":"EMBO Mol Med"},{"issue":"1","key":"313_CR5","doi-asserted-by":"publisher","first-page":"e20190945","DOI":"10.1084\/jem.20190945","volume":"217","author":"JA Hamilton","year":"2020","unstructured":"Hamilton JA. GM-CSF in inflammation. J Exp Med. 2020;217(1):e20190945.","journal-title":"J Exp Med"},{"issue":"1","key":"313_CR6","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/nrd.2016.231","volume":"16","author":"JA Hamilton","year":"2016","unstructured":"Hamilton JA, Cook AD, Tak PP. Anti-colony-stimulating factor therapies for inflammatory and autoimmune diseases. Nat Rev Drug Discov. 2016;16(1):53\u201370.","journal-title":"Nat Rev Drug Discov"},{"issue":"2","key":"313_CR7","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","volume":"181","author":"M Hoffmann","year":"2020","unstructured":"Hoffmann M, Kleine-Weber H, Schroeder S, Kr\u00c3ger N, Herrler T, Erichsen S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271\u201380.","journal-title":"Cell"},{"issue":"11","key":"313_CR8","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1164\/rccm.202005-1885OC","volume":"202","author":"S Hue","year":"2020","unstructured":"Hue S, Beldi-Ferchiou A, Bendib I, Surenaud M, Fourati S, Frapard T, et al. Uncontrolled innate and impaired adaptive immune responses in patients with COVID-19 ARDS. Am J Respir Crit Care Med. 2020;202(11):1509\u201319.","journal-title":"Am J Respir Crit Care Med"},{"issue":"8","key":"313_CR9","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1038\/s41577-020-0357-7","volume":"20","author":"FM Lang","year":"2020","unstructured":"Lang FM, Lee KM, Teijaro JR, Becher B, Hamilton JA. GM-CSF-based treatments in COVID-19: reconciling opposing therapeutic approaches. Nat Rev Immunol. 2020;20(8):507\u201314.","journal-title":"Nat Rev Immunol"},{"issue":"8","key":"313_CR10","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/S2213-2600(20)30267-8","volume":"8","author":"P Mehta","year":"2020","unstructured":"Mehta P, Porter JC, Manson JJ, Isaacs JD, Openshaw PJM, McInnes IB, Summers C, Chambers RC. Therapeutic blockade of granulocyte macrophage colony-stimulating factor in COVID-19-associated hyperinflammation: challenges and opportunities. Lancet Respir Med. 2020;8(8):822\u201330.","journal-title":"Lancet Respir Med"},{"issue":"7815","key":"313_CR11","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/s41586-020-2349-y","volume":"583","author":"D Pinto","year":"2020","unstructured":"Pinto D, Park YJ, Beltramello M, Walls AC, Tortorici MA, Bianchi S, et al. Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature. 2020;583(7815):290\u20135.","journal-title":"Nature"},{"key":"313_CR12","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3COVCRA0920-628RR","author":"X Qiang","year":"2021","unstructured":"Qiang X, Zhu S, Li J, Chen W, Yang H, Wang P, Tracey KJ, Wang H. Monoclonal antibodies capable of binding SARS-CoV-2 spike protein receptor-binding motif specifically prevent GM-CSF induction. J Leukoc Biol. 2021. https:\/\/doi.org\/10.1002\/JLB.3COVCRA0920-628RR.","journal-title":"J Leukoc Biol"},{"issue":"6506","key":"313_CR13","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1126\/science.abc7520","volume":"369","author":"TF Rogers","year":"2020","unstructured":"Rogers TF, Zhao F, Huang D, Beutler N, Burns A, He WT, et al. Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model. Science. 2020;369(6506):956\u201363.","journal-title":"Science"},{"issue":"11","key":"313_CR14","doi-asserted-by":"publisher","first-page":"2382","DOI":"10.1016\/j.mayocp.2020.08.038","volume":"95","author":"Z Temesgen","year":"2020","unstructured":"Temesgen Z, Assi M, Shweta FNU, Vergidis P, Rizza SA, Bauer PR, et al. GM-CSF neutralization with lenzilumab in severe COVID-19 pneumonia: a case-cohort study. Mayo Clin Proc. 2020;95(11):2382\u201394.","journal-title":"Mayo Clin Proc"},{"issue":"57","key":"313_CR15","doi-asserted-by":"publisher","first-page":"eabg9873","DOI":"10.1126\/sciimmunol.abg9873","volume":"6","author":"RS Thwaites","year":"2021","unstructured":"Thwaites RS, Sanchez Sevilla UA, Siggins MK, Liew F, Russell CD, Moore SC, et al. Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19. Sci Immunol. 2021;6(57):eabg9873.","journal-title":"Sci Immunol"},{"issue":"6483","key":"313_CR16","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1126\/science.abb2507","volume":"367","author":"D Wrapp","year":"2020","unstructured":"Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, Graham BS, McLellan JS. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260\u20133.","journal-title":"Science"},{"issue":"109","key":"313_CR17","first-page":"13","volume":"2021","author":"D Zhang","year":"2020","unstructured":"Zhang D, Guo R, Lei L, Liu H, Wang Y, Wang Y, et al. COVID-19 infection induces readily detectable morphologic and inflammation-related phenotypic changes in peripheral blood monocytes. J Leukoc Biol. 2020;2021(109):13\u201322.","journal-title":"J Leukoc Biol"},{"issue":"56","key":"313_CR18","doi-asserted-by":"publisher","first-page":"eabf6692","DOI":"10.1126\/sciimmunol.abf6692","volume":"6","author":"Y Zhao","year":"2021","unstructured":"Zhao Y, Kilian C, Turner JE, Bosurgi L, Roedl K, Bartsch P, et al. Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in the lungs of severe COVID-19 patients. Sci Immunol. 2021;6(56):eabf6692.","journal-title":"Sci Immunol"},{"issue":"7821","key":"313_CR19","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1038\/s41586-020-2548-6","volume":"584","author":"SJ Zost","year":"2020","unstructured":"Zost SJ, Gilchuk P, Case JB, Binshtein E, Chen RE, Nkolola JP, et al. Potently neutralizing and protective human antibodies against SARS-CoV-2. Nature. 2020;584(7821):443\u20139.","journal-title":"Nature"}],"container-title":["Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10020-021-00313-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s10020-021-00313-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10020-021-00313-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,22]],"date-time":"2021-05-22T13:11:43Z","timestamp":1621689103000},"score":1,"resource":{"primary":{"URL":"https:\/\/molmed.biomedcentral.com\/articles\/10.1186\/s10020-021-00313-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,22]]},"references-count":19,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["313"],"URL":"https:\/\/doi.org\/10.1186\/s10020-021-00313-3","relation":{},"ISSN":["1076-1551","1528-3658"],"issn-type":[{"type":"print","value":"1076-1551"},{"type":"electronic","value":"1528-3658"}],"subject":[],"published":{"date-parts":[[2021,5,22]]},"assertion":[{"value":"31 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"H.W., J.L., and K.J.T. are co-inventors of a patent application (\u201c<i>Tetranectin-targeting monoclonal antibodies to fight against lethal sepsis and other pathologies<\/i>\u201d) and a provisional patent application <i>(\u201cUse of SARS-CoV-2 receptor binding motif (RBM)-reactive monoclonal antibodies to treat COVID-19\u201d<\/i>). All other authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"49"}}