{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:44:30Z","timestamp":1790117070073,"version":"4.0.1"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), a highly pathogenic coronavirus (CoV) belonging to Coronavirus B, has triggered outbreaks or pandemics. Currently, many variants of SARS-CoV-2 have evolved, which exhibit severe immune evasion and imprinting resistance to existing vaccines and cause infected individuals to develop Post-Acute Sequelae of SARS-CoV-2 (also termed Long-COVID). This underscores the public health importance of developing effective vaccines with broad-spectrum efficacy against the SARS-CoV-2 variant and other CoVs with pandemic potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this study, we expressed three tandem-repeat dimeric recombinant RBD proteins using an insect-baculovirus expression system integrated with the high-frequency SARS-CoV-2 RBD mutation sites. We performed immunogenicity assessment and attack protection tests. The date showed that these innovative SARS-CoV-2 RBD recombinant protein vaccines could show varying degrees of cross-immunity response and potent protection against SARS-CoV-2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, our results indicated that these recombinant RBD subunit vaccines could serves a promising platform for a universal vaccine against SARS-CoV-2 and its variants, and provide a new perspective for the design of other future pandemic vaccines.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1806270","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T05:43:17Z","timestamp":1780983797000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Recombinant RBD-based subunit vaccines incorporating high-frequency mutation sites elicit cross-immunity and robust protection against SARS-CoV-2"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhiguang","family":"Ren","sequence":"first","affiliation":[{"name":"Henan Intelligent Diagnosis and Treatment Engineering Technology Research Center, The First Affiliated Hospital, Henan University","place":["Kaifeng, China"]},{"name":"Key Laboratory of Jilin Province for Zoonoses Prevention and Control, National Key Laboratory of Pathogen Microorganisms Biosafety, Academy of Military Medical Sciences","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiawei","family":"Liu","sequence":"additional","affiliation":[{"name":"Henan Intelligent Diagnosis and Treatment Engineering Technology Research Center, The First Affiliated Hospital, Henan University","place":["Kaifeng, China"]},{"name":"State Key Laboratory of Antiviral Drugs, School of Pharmacy, School of Basic Medicine Sciences, Henan University","place":["Kaifeng, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyang","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Antiviral Drugs, School of Pharmacy, School of Basic Medicine Sciences, Henan University","place":["Kaifeng, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Henan Intelligent Diagnosis and Treatment Engineering Technology Research Center, The First Affiliated Hospital, Henan University","place":["Kaifeng, China"]},{"name":"Key Laboratory of Jilin Province for Zoonoses Prevention and Control, National Key Laboratory of Pathogen Microorganisms Biosafety, Academy of Military Medical Sciences","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Li","sequence":"additional","affiliation":[{"name":"Henan Intelligent Diagnosis and Treatment Engineering Technology Research Center, The First Affiliated Hospital, Henan University","place":["Kaifeng, China"]},{"name":"Key Laboratory of Jilin Province for Zoonoses Prevention and Control, National Key Laboratory of Pathogen Microorganisms Biosafety, Academy of Military Medical Sciences","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Jilin Province for Zoonoses Prevention and Control, National Key Laboratory of Pathogen Microorganisms Biosafety, Academy of Military Medical Sciences","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyu","family":"Hu","sequence":"additional","affiliation":[{"name":"Henan Intelligent Diagnosis and Treatment Engineering Technology Research Center, The First Affiliated Hospital, Henan University","place":["Kaifeng, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Henan Intelligent Diagnosis and Treatment Engineering Technology Research Center, The First Affiliated Hospital, Henan University","place":["Kaifeng, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongkun","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Antiviral Drugs, School of Pharmacy, School of Basic Medicine Sciences, Henan University","place":["Kaifeng, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanguo","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Antiviral Drugs, School of Pharmacy, School of Basic Medicine Sciences, Henan University","place":["Kaifeng, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianzhu","family":"Xia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Antiviral Drugs, School of Pharmacy, School of Basic Medicine Sciences, Henan University","place":["Kaifeng, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyan","family":"Yang","sequence":"additional","affiliation":[{"name":"Henan Intelligent Diagnosis and Treatment Engineering Technology Research Center, The First Affiliated Hospital, Henan University","place":["Kaifeng, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"Henan Intelligent Diagnosis and Treatment Engineering Technology Research Center, The First Affiliated Hospital, Henan University","place":["Kaifeng, China"]},{"name":"Key Laboratory of Jilin Province for Zoonoses Prevention and Control, National Key Laboratory of Pathogen Microorganisms Biosafety, Academy of Military Medical Sciences","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrui","family":"Lv","sequence":"additional","affiliation":[{"name":"Henan Intelligent Diagnosis and Treatment Engineering Technology Research Center, The First Affiliated Hospital, Henan University","place":["Kaifeng, China"]},{"name":"Kaifeng Key Laboratory for Infectious Diseases and Biosafety, The First Affiliated Hospital of Henan University","place":["Kaifeng, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiecheng","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Antiviral Drugs, School of Pharmacy, School of Basic Medicine Sciences, Henan University","place":["Kaifeng, China"]},{"name":"Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University","place":["Yangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daxiang","family":"Cui","sequence":"additional","affiliation":[{"name":"Henan Intelligent Diagnosis and Treatment Engineering Technology Research Center, The First Affiliated Hospital, Henan University","place":["Kaifeng, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2351664","DOI":"10.1080\/21645515.2024.2351664","article-title":"Characterization and immunogenicity assessment of Mers-Cov pre-fusion spike trimeric oligomers as vaccine immunogen","volume":"20","author":"Ahuja","year":"2024","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"119881","DOI":"10.1016\/j.cca.2024.119881","article-title":"Blood proteomics of Covid-19 infection: An update","volume":"562","author":"Alexovi\u010d","year":"2024","journal-title":"Clin. Chim. Acta"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1038\/s41392-024-02007-8","article-title":"A protein vaccine of RBD integrated with immune evasion mutation shows broad protection against Sars-Cov-2","volume":"9","author":"An","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e0365523","DOI":"10.1128\/spectrum.03655-23","article-title":"Characterization of a neutralizing antibody that recognizes a loop region adjacent to the receptor-binding interface of the Sars-Cov-2 spike receptor-binding domain","volume":"12","author":"Anzai","year":"2024","journal-title":"Microbiol. Spectrum"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e70658","DOI":"10.7554\/eLife.70658","article-title":"Effects of common mutations in the Sars-Cov-2 spike Rbd and its ligand, the human Ace2 receptor on binding affinity and kinetics","volume":"10","author":"Barton","year":"2021","journal-title":"eLife"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e2350873","DOI":"10.1002\/eji.202350873","article-title":"Intestinal tissue-resident memory T cells maintain distinct identity from circulating memory T cells after in vitro restimulation","volume":"54","author":"Beumer-Chuwonpad","year":"2024","journal-title":"Eur. J. Immunol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"111353","DOI":"10.1016\/j.jtbi.2022.111353","article-title":"Exploring the role of superspreading events in Sars-Cov-2 outbreaks","volume":"558","author":"Bramble","year":"2023","journal-title":"J. Theor. Biol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1038\/s41467-023-36745-0","article-title":"Structural dynamics in the evolution of Sars-Cov-2 spike glycoprotein","volume":"14","author":"Calvaresi","year":"2023","journal-title":"Nat. Commun."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"108974","DOI":"10.1016\/j.celrep.2021.108974","article-title":"High-dimensional profiling clusters asthma severity by lymphoid and non-lymphoid status","volume":"35","author":"Camiolo","year":"2021","journal-title":"Cell Rep."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"115036","DOI":"10.1016\/j.celrep.2024.115036","article-title":"Protein nanoparticle vaccines induce potent neutralizing antibody responses against Mers-Cov","volume":"43","author":"Chao","year":"2024","journal-title":"Cell Rep."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1038\/nm.2628","article-title":"An essential role for Th2-type responses in limiting acute tissue damage during experimental helminth infection","volume":"18","author":"Chen","year":"2012","journal-title":"Nat. Med."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/s41577-020-00480-0","article-title":"Viral targets for vaccines against Covid-19","volume":"21","author":"Dai","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"2097","DOI":"10.1056\/NEJMoa2202261","article-title":"Efficacy and safety of the Rbd-dimer-based Covid-19 vaccine Zf2001 in adults","volume":"386","author":"Dai","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1038\/s41586-022-04690-5","article-title":"Defining the risk of Sars-Cov-2 variants on immune protection","volume":"605","author":"DeGrace","year":"2022","journal-title":"Nature"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"112266","DOI":"10.1016\/j.celrep.2023.112266","article-title":"Design of a stabilized Rbd enables potently neutralizing Sars-Cov-2 single-component nanoparticle vaccines","volume":"42","author":"Dickey","year":"2023","journal-title":"Cell Rep."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1084\/jem.20091627","article-title":"Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8\u03b1+ conventional dendritic cells","volume":"207","author":"Edelson","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"e0186522","DOI":"10.1128\/jvi.01865-22","article-title":"All domains of Sars-Cov-2 Nsp1 determine translational shutoff and cytotoxicity of the protein","volume":"97","author":"Frolov","year":"2023","journal-title":"J. Virol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/s2352-4642(22)00376-5","article-title":"Safety and immunogenicity of a protein subunit Covid-19 vaccine (Zf2001) in healthy children and adolescents aged 3-17 years in China: a randomised, double-blind, placebo-controlled, phase 1 trial and an open-label, non-randomised, non-inferiority, phase 2 trial","volume":"7","author":"Gao","year":"2023","journal-title":"Lancet Child Adolesc. Health"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1016\/j.cell.2022.01.001","article-title":"Receptor binding and complex structures of human Ace2 to spike Rbd from omicron and Delta Sars-Cov-2","volume":"185","author":"Han","year":"2022","journal-title":"Cell"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3310\/yapl9347","article-title":"Ceftazidime with avibactam for treating severe aerobic gram-negative bacterial infections: technology evaluation to inform a novel subscription-style payment model","volume":"28","author":"Harnan","year":"2024","journal-title":"Health Technol. Assess."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"3276","DOI":"10.1080\/21645515.2021.1945901","article-title":"Landscape and Progress of global Covid-19 vaccine development","volume":"17","author":"Huang","year":"2021","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"fuae023","DOI":"10.1093\/femsre\/fuae023","article-title":"The emerging role of Sars-Cov-2 nonstructural protein 1 (Nsp1) in epigenetic regulation of host gene expression","volume":"48","author":"Ivanov","year":"2024","journal-title":"FEMS Microbiol. Rev."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"974016","DOI":"10.3389\/fimmu.2022.974016","article-title":"RIG-I and TLR-7\/8 agonists as combination adjuvant shapes unique antibody and cellular vaccine responses to seasonal influenza vaccine","volume":"13","author":"Jangra","year":"2022","journal-title":"Front. Immunol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"2738","DOI":"10.1021\/acsnano.0c08379","article-title":"Rapid development of Sars-Cov-2 spike protein receptor-binding domain self-assembled nanoparticle vaccine candidates","volume":"15","author":"Kang","year":"2021","journal-title":"ACS Nano"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1016\/j.bbi.2024.10.032","article-title":"Sars-Cov-2 variants mediated tissue-specific metabolic reprogramming determines the disease pathophysiology in a Hamster model","volume":"123","author":"Kaur Sardarni","year":"2025","journal-title":"Brain Behav. Immun."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"151558","DOI":"10.1016\/j.bbrc.2025.151558","article-title":"Structure and dynamics of alpha B.1.1.7 Sars-Cov-2 S-protein in complex with fab of neutralizing antibody Regn10987","volume":"755","author":"Kocharovskaya","year":"2025","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1080\/14760584.2022.2081156","article-title":"The chimera of S1 and N proteins of Sars-Cov-2: can it be a potential vaccine candidate for Covid-19?","volume":"21","author":"Kumar","year":"2022","journal-title":"Expert Rev. Vaccines"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1016\/j.str.2024.06.012","article-title":"Spike structures, receptor binding, and immune escape of recently circulating Sars-Cov-2 omicron Ba.2.86, Jn.1, Eg.5, Eg.5.1, and Hv.1 sub-variants","volume":"32","author":"Li","year":"2024","journal-title":"Structure"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e2107461","DOI":"10.1002\/smll.202107461","article-title":"Antigen capture and immune modulation by bacterial outer membrane vesicles as in situ vaccine for Cancer immunotherapy Post-Photothermal therapy","volume":"18","author":"Li","year":"2022","journal-title":"Small"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1475431","DOI":"10.3389\/fvets.2024.1475431","article-title":"Rabies virus as vector for development of vaccine: pros and cons","volume":"11","author":"Li","year":"2024","journal-title":"Front. Vet. Sci."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/s41541-025-01066-4","article-title":"Mrna vaccines with RBD mutations have broad-spectrum activity against Sars-Cov-2 variants in mice","volume":"10","author":"Liang","year":"2025","journal-title":"NPJ Vaccines"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/s41421-022-00383-5","article-title":"Design of a mutation-integrated trimeric Rbd with broad protection against Sars-Cov-2","volume":"8","author":"Liang","year":"2022","journal-title":"Cell Discov."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1016\/j.chom.2023.06.002","article-title":"The Nsp4 T492i mutation increases Sars-Cov-2 infectivity by altering non-structural protein cleavage","volume":"31","author":"Lin","year":"2023","journal-title":"Cell Host Microbe"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"136403","DOI":"10.1016\/j.ijbiomac.2024.136403","article-title":"Identification of a potent Sars-Cov-2 neutralizing nanobody targeting the receptor-binding domain of the spike protein","volume":"281","author":"Liu","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref35","doi-asserted-by":"publisher","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":"ref36","doi-asserted-by":"publisher","first-page":"110495","DOI":"10.1016\/j.cellsig.2022.110495","article-title":"Covid-19 signalome: pathways for Sars-Cov-2 infection and impact on Covid-19 associated comorbidity","volume":"101","author":"Lundstrom","year":"2023","journal-title":"Cell. Signal."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.4049\/jimmunol.2200731","article-title":"Recombinant Bacillus Calmette-Gu\u00e9rin expressing Sars-Cov-2 chimeric protein protects K18-Hace2 mice against viral challenge","volume":"210","author":"Mambelli","year":"2023","journal-title":"J. Immunol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"e0115723","DOI":"10.1128\/jvi.01157-23","article-title":"Structural basis and analysis of hamster Ace2 binding to different Sars-Cov-2 spike Rbds","volume":"98","author":"Niu","year":"2024","journal-title":"J. Virol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1111\/cmi.12658","article-title":"Bacterial membrane vesicles: biogenesis, immune regulation and pathogenesis","volume":"18","author":"Pathirana","year":"2016","journal-title":"Cell. Microbiol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"2539","DOI":"10.1038\/s41467-022-30195-w","article-title":"Sars-Cov-2 infection induces inflammatory bone loss in golden Syrian hamsters","volume":"13","author":"Qiao","year":"2022","journal-title":"Nat. Commun."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"e0012252","DOI":"10.1371\/journal.pntd.0012252","article-title":"Review of genotyping methods for Yersinia pestis in Madagascar","volume":"18","author":"Randriantseheno","year":"2024","journal-title":"PLoS Negl. Trop. Dis."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.12998\/wjcc.v10.i1.1","article-title":"Omicron variant (B.1.1.529) of Sars-Cov-2: mutation, infectivity, transmission, and vaccine resistance","volume":"10","author":"Ren","year":"2022","journal-title":"World J. Clin. Cases"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1038\/s41586-021-04266-9","article-title":"Enhanced fusogenicity and pathogenicity of Sars-Cov-2 Delta P681r mutation","volume":"602","author":"Saito","year":"2022","journal-title":"Nature"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/s42003-021-02265-0","article-title":"I(Nsp1)ecting Sars-Cov-2-ribosome interactions","volume":"4","author":"Simeoni","year":"2021","journal-title":"Commun. Biol."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/334255a0","article-title":"Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells","volume":"334","author":"Stevens","year":"1988","journal-title":"Nature"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1126\/science.abc8665","article-title":"Structural basis for translational shutdown and immune evasion by the Nsp1 protein of Sars-Cov-2","volume":"369","author":"Thoms","year":"2020","journal-title":"Science"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"eadl5762","DOI":"10.1126\/sciadv.adl5762","article-title":"Longitudinal plasma proteomic analysis of 1117 hospitalized patients with Covid-19 identifies features associated with severity and outcomes","volume":"10","author":"Viode","year":"2024","journal-title":"Sci. Adv."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1910","DOI":"10.1080\/22221751.2022.2088406","article-title":"Efficacy of heterologous boosting against Sars-Cov-2 using a recombinant interferon-armed fusion protein vaccine (V-01): a randomized, double-blind and placebo-controlled phase iii trial","volume":"11","author":"Wang","year":"2022","journal-title":"Emerg. Microbes Infect."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1038\/s41421-023-00575-7","article-title":"Impact of Sars-Cov-2 envelope protein mutations on the pathogenicity of omicron Xbb","volume":"9","author":"Wang","year":"2023","journal-title":"Cell Discov."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"e0037624","DOI":"10.1128\/jvi.00376-24","article-title":"Pan-beta-coronavirus subunit vaccine prevents Sars-Cov-2 omicron, Sars-Cov, and Mers-Cov challenge","volume":"98","author":"Wang","year":"2024","journal-title":"J. Virol."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1016\/j.cell.2020.03.045","article-title":"Structural and functional basis of Sars-Cov-2 entry by using human Ace2","volume":"181","author":"Wang","year":"2020","journal-title":"Cell"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1126\/science.abb2507","article-title":"Cryo-Em structure of the 2019-Ncov spike in the Prefusion conformation","volume":"367","author":"Wrapp","year":"2020","journal-title":"Science"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"3021","DOI":"10.1038\/s41401-021-00851-w","article-title":"Structure genomics of Sars-Cov-2 and its omicron variant: drug design templates for Covid-19","volume":"43","author":"Wu","year":"2022","journal-title":"Acta Pharmacol. Sin."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"100251","DOI":"10.1016\/j.xinn.2022.100251","article-title":"Why is the Sars-Cov-2 omicron variant milder?","volume":"3","author":"Xia","year":"2022","journal-title":"Int. J. Hydrogen Energ."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.1016\/j.cell.2022.04.029","article-title":"Protective prototype-beta and delta-omicron chimeric Rbd-dimer vaccines against Sars-Cov-2","volume":"185","author":"Xu","year":"2022","journal-title":"Cell"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"eabe5575","DOI":"10.1126\/sciadv.abe5575","article-title":"Conformational dynamics of Sars-Cov-2 trimeric spike glycoprotein in complex with receptor Ace2 revealed by Cryo-Em","volume":"7","author":"Xu","year":"2021","journal-title":"Sci. Adv."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1093\/procel\/pwae007","article-title":"Mutations in the Sars-Cov-2 spike receptor binding domain and their delicate balance between Ace2 affinity and antibody evasion","volume":"15","author":"Xue","year":"2024","journal-title":"Protein Cell"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"2191577","DOI":"10.1080\/21645515.2023.2191577","article-title":"Tracking the Covid-19 vaccines: the global landscape","volume":"19","author":"Yadav","year":"2023","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1016\/s1473-3099(21)00127-4","article-title":"Safety and immunogenicity of a recombinant tandem-repeat dimeric Rbd-based protein subunit vaccine (Zf2001) against Covid-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials","volume":"21","author":"Yang","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"E23","DOI":"10.1038\/s41586-020-03108-4","article-title":"Publisher correction: a vaccine targeting the Rbd of the S protein of Sars-Cov-2 induces protective immunity","volume":"590","author":"Yang","year":"2021","journal-title":"Nature"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1038\/s41586-020-2599-8","article-title":"A vaccine targeting the Rbd of the S protein of Sars-Cov-2 induces protective immunity","volume":"586","author":"Yang","year":"2020","journal-title":"Nature"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1016\/j.molcel.2020.10.034","article-title":"Nonstructural protein 1 of Sars-Cov-2 is a potent pathogenicity factor redirecting host protein synthesis machinery toward viral Rna","volume":"80","author":"Yuan","year":"2020","journal-title":"Mol. Cell"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"e78633","DOI":"10.7554\/eLife.78633","article-title":"A mosaic-type trimeric Rbd-based Covid-19 vaccine candidate induces potent neutralization against omicron and other Sars-Cov-2 variants","volume":"11","author":"Zhang","year":"2022","journal-title":"eLife"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.virs.2022.12.006","article-title":"An inactivated recombinant rabies virus chimerically expressed RBD induces humoral and cellular immunity against Sars-Cov-2 and Rabv","volume":"38","author":"Zhang","year":"2023","journal-title":"Virol. Sin."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"e1011659","DOI":"10.1371\/journal.ppat.1011659","article-title":"Broad protective Rbd heterotrimer vaccines neutralize Sars-Cov-2 including omicron sub-variants Xbb\/Bq.1.1\/bf.7","volume":"19","author":"Zhang","year":"2023","journal-title":"PLoS Pathog."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"109925","DOI":"10.1016\/j.virol.2023.109925","article-title":"A potent neutralizing nanobody targeting a unique epitope on the receptor-binding domain of Sars-Cov-2 spike protein","volume":"589","author":"Zhang","year":"2024","journal-title":"Virology"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"1407826","DOI":"10.3389\/fimmu.2024.1407826","article-title":"Efficacy, safety, and immunogenicity of Sars-Cov-2 Mrna vaccine (omicron Ba.5) Lvrna012: a randomized, double-blind, placebo-controlled phase 3 trial","volume":"15","author":"Zhou","year":"2024","journal-title":"Front. Immunol."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s12931-025-03143-7","article-title":"Acute lung injury induced by recombinant Sars-Cov-2 spike protein subunit S1 in mice","volume":"26","author":"Zhu","year":"2025","journal-title":"Respir. Res."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A novel coronavirus from patients with pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N. Engl. J. Med."}],"updated-by":[{"DOI":"10.3389\/fmicb.2026.1925275","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000}}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1806270\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T20:44:37Z","timestamp":1784753077000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1806270\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,9]]},"references-count":69,"alternative-id":["10.3389\/fmicb.2026.1806270"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1806270","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,9]]},"article-number":"1806270"}}