A mosaic-type trimeric RBD-based COVID-19 vaccine candidate induces potent neutralization against Omicron and other SARS-CoV-2 variants

• DOI: 10.7554/elife.78633
• Publication Date: 2022-08-25T10:00:24Z
• Authors: Jing Zhang; Zi Bo Han; Yu Liang; Xue Feng Zhang; Yu Qin Jin; Li Fang Du; Shuai Shao; Hui Wang; Jun Wei Hou; Ke Xu; Wenwen Lei; Ze Hua Lei; Zhao Ming Liu; Jin Zhang; Ya Nan Hou; Ning Liu; Fu Jie Shen; Jin Juan Wu; Xiang Zheng; Xin Yu Li; Xin Li; Wei Jin Huang; Gui Zhen Wu; Ji Guo Su; Qi Ming Li
• Keywords: Infectious disease (medical specialty); FOS: Health sciences; Antibodies, Viral; Prediction of Peptide-MHC Binding Affinity; Coronavirus Disease 2019; immunology; Immunology and Inflammation; vaccine; Pathology; omicron variant; broad-spectrum; Disease; Viral; Biology (General); Neutralizing; Vaccines; Q; Vaccination; R; Life Sciences; Spike Glycoprotein; Virus; 3. Good health; Infectious Diseases; Spike Glycoprotein, Coronavirus; Medicine; Titer; COVID-19 Vaccines; QH301-705.5; infectious disease; Science; Immunology; Coronavirus Disease 2019 Research; Antibodies; Neutralization; Biochemistry, Genetics and Molecular Biology; Virology; Health Sciences; Animals; Humans; viruses; Molecular Biology; Biology; Antibody; Pandemic; SARS-CoV-2; FOS: Clinical medicine; microbiology; COVID-19; Neutralizing antibody; Antibodies, Neutralizing; Rats; Coronavirus; Coronavirus disease 2019 (COVID-19); inflammation; Broadly Neutralizing Antibodies

Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody ID50 titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the BIBP inactivated COVID-19 vaccine (BBIBP-CorV). Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.