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J Med Virol . Broadly Protective Antibody-Like Vaccines Against Highly Pathogenic Coronaviruses

tetano

Editor, Senior Moderator
J Med Virol


. 2026 Jun;98(6):e71008.
doi: 10.1002/jmv.71008.
Broadly Protective Antibody-Like Vaccines Against Highly Pathogenic Coronaviruses

Assala Helal[SUP] 1 2 [/SUP], Najwa D Aljehani[SUP] 1 [/SUP], Aishah Ghazwani[SUP] 1 3 [/SUP], Reem M Alsulaiman[SUP] 1 [/SUP], Faris Alyami[SUP] 1 [/SUP], Wesam H Abdulaal[SUP] 3 [/SUP], Asem Alsharef[SUP] 1 3 [/SUP], Maimonah Alghanmi[SUP] 1 4 [/SUP], Ayat Zawawi[SUP] 1 4 [/SUP], Ala A Azhari[SUP] 1 5 [/SUP], Afnan Almehmadi[SUP] 1 [/SUP], Jood Balula[SUP] 1 [/SUP], Tarfa Altorki[SUP] 1 4 [/SUP], Rowa Y Alhabbab[SUP] 1 4 [/SUP], Muhammad Yasir Khan[SUP] 1 [/SUP], Khalid Alluhaybi[SUP] 1 6 [/SUP], Aisha Alnami[SUP] 1 7 [/SUP], Thikryat Neamatallah[SUP] 2 [/SUP], Turki S Abujamel[SUP] 1 4 [/SUP], Mohamed A Alfaleh[SUP] 1 [/SUP], Anwar M Hashem[SUP] 1 5 [/SUP]


Affiliations
Abstract

SARS-CoV-2 and MERS-CoV are highly pathogenic and contagious coronaviruses. Despite intensive vaccination, SARS-CoV-2 continues to spread, and no FDA-approved vaccines exist for MERS-CoV; thus, more effective and safer vaccine options are needed. The receptor-binding domain (RBD) of coronaviruses is a primary target of neutralizing antibodies (nAbs); therefore, we generated three bivalent IgG1 Fc-fusion vaccines (BiVaxs) combining SARS-CoV-2 and MERS-CoV RBDs. The BiVax[SUB]Fc-Native[/SUB] vaccine comprises [SUP]omicron's-RBD[/SUP]SARS-CoV-2 fused to the native Fc C-terminus and [SUP]RBD[/SUP]MERS-CoV to the N-terminus. The BiVax[SUB]Fc-Reverse[/SUB] vaccine has a native Fc, yet [SUP]RBD[/SUP]MERS-CoV was fused to the C-terminus, and the [SUP]omicron's-RBD[/SUP]SARS-CoV-2 to the N-terminus. The third was BiVax[SUB]Fc-FcRn[/SUB], which is similar to BiVax[SUB]Fc-Native[/SUB], although it contains MST-HN Fc mutations (M252Y/S254T/T256E-H433K/N434F) to enhance neonatal Fc receptor (FcRn) binding on antigen-presenting cells (APCs). In mice, BiVax[SUB]Fc-FcRn[/SUB] showed significantly higher immunogenicity than the other two forms. It induced robust IgG and nAb responses against [SUP]RBD[/SUP]MERS-CoV after two doses and moderate responses [SUP]omicron's-RBD[/SUP]SARS-CoV-2 after the third dose. Remarkably, it also generated strong cross-reactive antibodies against SARS-CoV-1. These findings suggest that [SUP]RBD[/SUP]MERS-CoV is more immunogenic than [SUP]omicron's-RBD[/SUP]SARS-CoV-2, and that BiVax[SUB]Fc-FcRn[/SUB] has a high potential for further development as a broad-spectrum vaccine platform to prevent infection with the targeted coronaviruses as well as future emerging viruses.

Keywords: Fc‐fusion; MERS‐CoV; SARS‐CoV‐2; antibodies; coronaviruses; vaccines.

 
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