{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T08:02:23Z","timestamp":1771660943531,"version":"3.50.1"},"reference-count":24,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82041025 and 92169112"],"award-info":[{"award-number":["82041025 and 92169112"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scientific Research Foundation of Zhejiang University City College","award":["J-202106"],"award-info":[{"award-number":["J-202106"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFC2300703"],"award-info":[{"award-number":["2021YFC2300703"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012247","name":"Program of Shanghai Academic\/Technology Research Leader","doi-asserted-by":"publisher","award":["20XD1420300"],"award-info":[{"award-number":["20XD1420300"]}],"id":[{"id":"10.13039\/501100012247","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2021M700840"],"award-info":[{"award-number":["2021M700840"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become more serious because of the continuous emergence of variants of concern (VOC), thus calling for the development of broad-spectrum vaccines with greater efficacy. Adjuvants play important roles in enhancing the immunogenicity of protein-based subunit vaccines. In this study, we compared the effect of three adjuvants, including aluminum, nanoparticle manganese and MF59, on the immunogenicity of three protein-based COVID-19 vaccine candidates, including RBD-Fc, RBD and S-trimer. We found that the nanoparticle manganese adjuvant elicited the highest titers of SARS-CoV-2 RBD-specific IgG, IgG1 and IgG2a, as well as neutralizing antibodies against infection by pseudotyped SARS-CoV-2 and its Delta variant. What is more, the nanoparticle manganese adjuvant effectively reduced the viral load of the authentic SARS-CoV-2 and Delta variant in the cell culture supernatants. These results suggest that nanoparticle manganese, known to facilitate cGAS-STING activation, is an optimal adjuvant for protein-based COVID-19 subunit vaccines.<\/jats:p>","DOI":"10.3390\/v14030501","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T20:11:57Z","timestamp":1646079117000},"page":"501","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Effect of Different Adjuvants on Immune Responses Elicited by Protein-Based Subunit Vaccines against SARS-CoV-2 and Its Delta Variant"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8906-1453","authenticated-orcid":false,"given":"Naru","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Medicine and Waikato Joint Institute, Zhejiang University City College, Hangzhou 310015, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianting","family":"Ji","sequence":"additional","affiliation":[{"name":"School of Medicine and Waikato Joint Institute, Zhejiang University City College, Hangzhou 310015, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7394-8084","authenticated-orcid":false,"given":"Zezhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaiming","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yubin","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5523-5841","authenticated-orcid":false,"given":"Kangchen","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine and Waikato Joint Institute, Zhejiang University City College, Hangzhou 310015, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sisi","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine and Waikato Joint Institute, Zhejiang University City College, Hangzhou 310015, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haotian","family":"Shang","sequence":"additional","affiliation":[{"name":"School of Medicine and Waikato Joint Institute, Zhejiang University City College, Hangzhou 310015, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zecan","family":"Shi","sequence":"additional","affiliation":[{"name":"School of Medicine and Waikato Joint Institute, Zhejiang University City College, Hangzhou 310015, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianyu","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Medicine and Waikato Joint Institute, Zhejiang University City College, Hangzhou 310015, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiawei","family":"Yao","sequence":"additional","affiliation":[{"name":"School of Medicine and Waikato Joint Institute, Zhejiang University City College, Hangzhou 310015, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2255-0391","authenticated-orcid":false,"given":"Lu","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7996-1119","authenticated-orcid":false,"given":"Shuofeng","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8283-7135","authenticated-orcid":false,"given":"Shibo","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/s41586-021-03470-x","article-title":"Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England","volume":"593","author":"Volz","year":"2021","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/s41586-021-03402-9","article-title":"Detection of a SARS-CoV-2 variant of concern in South Africa","volume":"592","author":"Tegally","year":"2021","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1126\/science.abh2644","article-title":"Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil","volume":"372","author":"Faria","year":"2021","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4220","DOI":"10.1016\/j.cell.2021.06.020","article-title":"Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum","volume":"184","author":"Liu","year":"2021","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1002\/jmv.27524","article-title":"Characterization of the novel SARS-CoV-2 Omicron (B.1.1.529) variant of concern and its global perspective","volume":"94","author":"Saxena","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_6","unstructured":"World Health Organization (2022, January 24). WHO Coronavirus (COVID-19) Dashboard. Available online: https:\/\/covid19.who.int\/."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jiph.2021.10.021","article-title":"Innovations and development of COVID-19 vaccines: A patent review","volume":"15","author":"Alshrari","year":"2022","journal-title":"J. Infect. Public Health"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1080\/22221751.2022.2030200","article-title":"Homologous or heterologous booster of inactivated vaccine reduces SARS-CoV-2 Omicron variant escape from neutralizing antibodies","volume":"11","author":"Wang","year":"2022","journal-title":"Emerg. Microbes Infect."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/s41586-021-03530-2","article-title":"Adjuvanting a subunit COVID-19 vaccine to induce protective immunity","volume":"594","author":"Arunachalam","year":"2021","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"589833","DOI":"10.3389\/fimmu.2020.589833","article-title":"Adjuvants for coronavirus vaccines","volume":"11","author":"Liang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Liu, Z., Zhou, J., Xu, W., Deng, W., Wang, Q., Wang, M., Wang, Q., Hsieh, M., Dong, J., and Wang, X. (2022). A novel STING agonist-adjuvanted Pan-sarbecovirus vaccine elicits potent and durable neutralizing antibody and T cell responses in mice, rabbits and NHPs. Cell Res., 1\u201319. Online ahead of print.","DOI":"10.1038\/s41422-022-00612-2"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1038\/s41423-021-00669-w","article-title":"Manganese salts function as potent adjuvants","volume":"18","author":"Zhang","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1007\/s12274-020-3243-5","article-title":"Manganese nanodepot augments host immune response against coronavirus","volume":"14","author":"Sun","year":"2020","journal-title":"Nano Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/cmi.2015.03","article-title":"Identification of an ideal adjuvant for receptor-binding domain-based subunit vaccines against Middle East respiratory syndrome coronavirus","volume":"13","author":"Zhang","year":"2016","journal-title":"Cell. Mol. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/s41392-020-00402-5","article-title":"RBD-Fc-based COVID-19 vaccine candidate induces highly potent SARS-CoV-2 neutralizing antibody response","volume":"5","author":"Liu","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/s41422-020-0305-x","article-title":"Inhibition of SARS-CoV-2 (previously 2019-nCoV) infection by a highly potent pan-coronavirus fusion inhibitor targeting its spike protein that harbors a high capacity to mediate membrane fusion","volume":"30","author":"Xia","year":"2020","journal-title":"Cell Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Liu, Z., Xu, W., Chen, Z., Fu, W., Zhan, W., Gao, Y., Zhou, J., Zhou, Y., Wu, J., and Wang, Q. (2021). An ultrapotent pan-\u03b2-coronavirus lineage B (\u03b2-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope. Protein Cell, 1\u201321. Online ahead of print.","DOI":"10.1007\/s13238-021-00871-6"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"108699","DOI":"10.1016\/j.celrep.2021.108699","article-title":"Enhancement versus neutralization by SARS-CoV-2 antibodies from a convalescent donor associates with distinct epitopes on the RBD","volume":"34","author":"Zhou","year":"2021","journal-title":"Cell Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1007\/s12250-020-00214-5","article-title":"Inefficiency of sera from mice treated with pseudotyped SARS-CoV to neutralize 2019-nCoV infection","volume":"35","author":"Liu","year":"2020","journal-title":"Virol. Sin."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1038\/s41564-020-00802-x","article-title":"Metallodrug ranitidine bismuth citrate suppresses SARS-CoV-2 replication and relieves virus-associated pneumonia in Syrian hamsters","volume":"5","author":"Yuan","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_21","first-page":"417","article-title":"Antibodies for COVID-19-which, when and how long?","volume":"35","author":"Theoharides","year":"2021","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_22","first-page":"423","article-title":"Monoclonal antibody therapy in COVID-19","volume":"35","author":"Conti","year":"2021","journal-title":"J Biol Regul Homeost Agents."},{"key":"ref_23","first-page":"843","article-title":"Management of patients at risk of anaphylaxis after COVID 19 vaccination","volume":"35","author":"Gangemi","year":"2021","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhang, N., Li, K., Liu, Z., Nandakumar, K.S., and Jiang, S. (2022). A Perspective on the Roles of Adjuvants in Developing Highly Potent COVID-19 Vaccines. Viruses, 14.","DOI":"10.3390\/v14020387"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/3\/501\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:29:40Z","timestamp":1760135380000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/3\/501"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,28]]},"references-count":24,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["v14030501"],"URL":"https:\/\/doi.org\/10.3390\/v14030501","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,28]]}}}