Three in one: An effective and universal vaccine expressing heterologous tandem RBD trimer by rabies virus vector protects mice against SARS-CoV-2

Jingbo Huang; Weiqi Wang; Hailun Li; Yujie Bai; Yumeng Song; Cuicui Jiao; Hongli Jin; Pei Huang; Haili Zhang; Xianzhu Xia; Feihu Yan; Yuanyuan Li; Hualei Wang

doi:10.1016/j.antiviral.2024.105905

Three in one: An effective and universal vaccine expressing heterologous tandem RBD trimer by rabies virus vector protects mice against SARS-CoV-2

Antiviral Res. 2024 May 11:227:105905. doi: 10.1016/j.antiviral.2024.105905. Online ahead of print.

Authors

Jingbo Huang¹, Weiqi Wang², Hailun Li³, Yujie Bai³, Yumeng Song³, Cuicui Jiao³, Hongli Jin⁴, Pei Huang³, Haili Zhang³, Xianzhu Xia², Feihu Yan², Yuanyuan Li³, Hualei Wang⁵

Affiliations

¹ State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China; Department of Chinese Medicine, The First Hospital of Jilin University, Changchun 130021, China.
² Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China.
³ State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China.
⁴ Changchun SR Biological Technology Co., LTD, Changchun 130012, Jilin, China.
⁵ State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun 130062, China. Electronic address: wanghualei@jlu.edu.cn.

PMID: 38740191
DOI: 10.1016/j.antiviral.2024.105905

Abstract

The rapid emergence of Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) variants, coupled with severe immune evasion and imprinting, has jeopardized the vaccine efficacy, necessitating urgent development of broad protective vaccines. Here, we propose a strategy employing recombinant rabies viruses (RABV) to create a universal SARS-CoV-2 vaccine expressing heterologous tandem receptor-binding domain (RBD) trimer from the SARS-CoV-2 Prototype, Delta, and Omicron strains (SRV-PDO). The results of mouse immunization indicated that SRV-PDO effectively induced cellular and humoral immune responses, and demonstrated higher immunogenicity and broader SARS-CoV-2 neutralization compared to the recombinant RABVs that only expressed RBD monomers. Moreover, SRV-PDO exhibited full protection against SARS-CoV-2 in the challenge assay. This study demonstrates that recombinant RABV expressing tandem RBD-heterotrimer as a multivalent immunogen could elicit a broad-spectrum immune response and potent protection against SARS-CoV-2, making it a promising candidate for future human or veterinary vaccines and offering a novel perspective in other vaccine design.

Keywords: Immunogens; RBD; Recombinant rabies virus; SARS-CoV-2; Tandem RBD-Heterotrimer; Universal vaccine.