Broadly Protective Antibody‐Like Vaccines Against Highly Pathogenic Coronaviruses
Assala Helal, Najwa D. Aljehani, Aishah Ghazwani, Reem M. Alsulaiman, Faris Alyami, Wesam H. Abdulaal, Asem Alsharef, Maimonah Alghanmi, Ayat Zawawi, Ala A. Azhari, Afnan Almehmadi, Jood Balula, Tarfa Altorki, Rowa Y. Alhabbab, Muhammad Yasir Khan, Khalid Alluhaybi, Aisha Alnami, Thikryat Neamatallah, Turki S. Abujamel, Mohamed A. Alfaleh, Anwar M. HashemABSTRACT
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 Fc‐Native vaccine comprises omicron's‐RBD SARS‐CoV‐2 fused to the native Fc C‐terminus and RBD MERS‐CoV to the N‐terminus. The BiVax Fc‐Reverse vaccine has a native Fc, yet RBD MERS‐CoV was fused to the C‐terminus, and the omicron's‐RBD SARS‐CoV‐2 to the N‐terminus. The third was BiVax Fc‐FcRn , which is similar to BiVax Fc‐Native , 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 Fc‐FcRn showed significantly higher immunogenicity than the other two forms. It induced robust IgG and nAb responses against RBD MERS‐CoV after two doses and moderate responses omicron's‐RBD SARS‐CoV‐2 after the third dose. Remarkably, it also generated strong cross‐reactive antibodies against SARS‐CoV‐1. These findings suggest that RBD MERS‐CoV is more immunogenic than omicron's‐RBD SARS‐CoV‐2, and that BiVax Fc‐FcRn 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.