{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T10:39:58Z","timestamp":1789382398483,"version":"build-2803163510"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T00:00:00Z","timestamp":1726531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T00:00:00Z","timestamp":1726531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["R01AI157975, R01AI139092, R01AI137472"],"award-info":[{"award-number":["R01AI157975, R01AI139092, R01AI137472"]}]},{"name":"HHS | National Institutes of Health","award":["R01AI157975, R01AI139092"],"award-info":[{"award-number":["R01AI157975, R01AI139092"]}]},{"name":"HHS | National Institutes of Health","award":["R01AI157975, R01AI139092, R01AI110700"],"award-info":[{"award-number":["R01AI157975, R01AI139092, R01AI110700"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2024,9,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>Three highly pathogenic coronaviruses (CoVs), SARS-CoV-2, SARS-CoV, and MERS-CoV, belonging to the genus beta-CoV, have caused outbreaks or pandemics. SARS-CoV-2 has evolved into many variants with increased resistance to the current vaccines. Spike (S) protein and its receptor-binding domain (RBD) fragment of these CoVs are important vaccine targets; however, the RBD of the SARS-CoV-2 Omicron variant is highly mutated, rending neutralizing antibodies elicited by ancestral-based vaccines targeting this region ineffective, emphasizing the need for effective vaccines with broad-spectrum efficacy against SARS-CoV-2 variants and other CoVs with pandemic potential. This study describes a pan-beta-CoV subunit vaccine, Om-S-MERS-RBD, by fusing the conserved and highly potent RBD of MERS-CoV into an RBD-truncated SARS-CoV-2 Omicron S protein, and evaluates its neutralizing immunogenicity and protective efficacy in mouse models. Om-S-MERS-RBD formed a conformational structure, maintained effective functionality and antigenicity, and bind efficiently to MERS-CoV receptor, human dipeptidyl peptidase 4, and MERS-CoV RBD or SARS-CoV-2 S-specific antibodies. Immunization of mice with Om-S-MERS-RBD and adjuvants (Alum plus monophosphoryl lipid A) induced broadly neutralizing antibodies against pseudotyped MERS-CoV, SARS-CoV, and SARS-CoV-2 original strain, as well as T-cell responses specific to RBD-truncated Omicron S protein. Moreover, the neutralizing activity against SARS-CoV-2 Omicron subvariants was effectively improved after priming with an Omicron-S-RBD protein. Adjuvanted Om-S-MERS-RBD protein protected mice against challenge with SARS-CoV-2 Omicron variant, MERS-CoV, and SARS-CoV, significantly reducing viral titers in the lungs. Overall, these findings indicated that Om-S-MERS-RBD protein could develop as an effective universal subunit vaccine to prevent infections with MERS-CoV, SARS-CoV, SARS-CoV-2, and its variants.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>Coronaviruses (CoVs), SARS-CoV-2, SARS-CoV, and MERS-CoV, the respective causative agents of coronavirus disease 2019, SARS, and MERS, continually threaten human health. The spike (S) protein and its receptor-binding domain (RBD) fragment of these CoVs are critical vaccine targets. Nevertheless, the highly mutated RBD of SARS-CoV-2 variants, especially Omicron, significantly reduces the efficacy of current vaccines against SARS-CoV-2 variants. Here a protein-based pan-beta-CoV subunit vaccine is designed by fusing the potent and conserved RBD of MERS-CoV into an RBD-truncated Omicron S protein. The resulting vaccine maintained effective functionality and antigenicity, induced broadly neutralizing antibodies against all of these highly pathogenic human CoVs, and elicited Omicron S-specific cellular immune responses, protecting immunized mice from SARS-CoV-2 Omicron, SARS-CoV, and MERS-CoV infections. Taken together, this study rationally designed a pan-beta-CoV subunit vaccine with broad-spectrum efficacy, which has the potential for development as an effective universal vaccine against SARS-CoV-2 variants and other CoVs with pandemic potential.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/jvi.00376-24","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T13:00:18Z","timestamp":1724763618000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["Pan-beta-coronavirus subunit vaccine prevents SARS-CoV-2 Omicron, SARS-CoV, and MERS-CoV challenge"],"prefix":"10.1128","volume":"98","author":[{"given":"Gang","family":"Wang","sequence":"first","affiliation":[{"name":"Institute for Biomedical Sciences, Georgia State University","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek K.","family":"Verma","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Iowa","place":["Iowa City, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Guan","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Sciences, Georgia State University","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Bu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Minnesota Medical School","place":["Minneapolis, USA"]},{"name":"Center for Coronavirus Research, University of Minnesota","place":["Minneapolis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abby E.","family":"Odle","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Iowa","place":["Iowa City, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1958-366X","authenticated-orcid":false,"given":"Fang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Minnesota Medical School","place":["Minneapolis, USA"]},{"name":"Center for Coronavirus Research, University of Minnesota","place":["Minneapolis, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6581-780X","authenticated-orcid":false,"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Hormel Institute, University of Minnesota","place":["Austin, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4213-2354","authenticated-orcid":false,"given":"Stanley","family":"Perlman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Iowa","place":["Iowa City, USA"]},{"name":"Department of Pediatrics, University of Iowa","place":["Iowa City, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5955-1294","authenticated-orcid":false,"given":"Lanying","family":"Du","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Sciences, Georgia State University","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1211721"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2090"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2012-7"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.00298"},{"key":"e_1_3_5_6_2","unstructured":"World Health Organization. 2024. 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