biostudies-literature00550Xu KSouthern University of Science and TechnologyChinese Academy of SciencesChina Postdoctoral Science FoundationNational Natural Science Foundation of ChinaInstitute of Microbiology, Chinese Academy of SciencesBill and Melinda Gates FoundationNational Key Research and Development Program of ChinaYouth Innovation Promotion Association of the Chinese Academy of Sciences2265-2278.e14https://www.ebi.ac.uk/biostudies/studies/S-EPMC9042943biostudies-literatureUnknown185(13)Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.CellProtective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2.PMC90429432020T130031ZXINV-027420201811382041048819914942020YFA09071008212203132100129Peng XQi JTang CWu CHan YLiu SGuo SHuang QWu GZhao ZWang JZhang RZhao XLiu XLiu YWang PWang SYu WAn YGao GFXu KDuan MXie YZhou YYang CZheng TGao PYang YDai LShe GLu SLei WLiu C55falseProtective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2.Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.2022-01-01T00:00:00Z2022 Jun2024-11-09T12:42:56.58Z2022-07-11T00:21:01.301ZS-EPMC90429433556803410.1016/j.cell.2022.04.029