RBD-HBsAg conjugated virus-like particle vaccine protects rhesus macaques from SARS-CoV-2 challenge

Abstract

The emergence of SARS-CoV-2, the etiologic agent of COVID-19, has caused an unprecedented global health burden, prompting the development of safe and efficacious countermeasures including vaccines. While enormous efforts have been undertaken to combat the pandemic, improving the designs of multiple COVID-19 vaccine candidates remains a global health imperative to overcome this crisis, especially as new variants emerge in regions across the world. In this study, we assessed the immunogenicity and protective efficacy of a virus-like particle (VLP) vaccine against SARS-CoV-2 challenge in rhesus macaques. The vaccine is based on a synthetic VLP platform in which the SARS-CoV-2 spike receptor-binding domain (RBD) is covalently conjugated to hepatitis B antigen (HBsAg) using the Spytag/SpyCatcher technology. Our data show that RBD-HBsAg VLP in conjunction with Alum elicited high levels of SARS-CoV-2 binding and neutralizing antibodies in macaques, and, concomitantly, protective immunity against the virus. Following SARS-CoV-2 challenge, the vaccinated macaques showed markedly reduced viral replication in the upper (nasal swabs) and lower respiratory tracts (bronchoalveolar lavages) compared to sham controls, indicating robust protection in the nares and lungs. Titers of vaccine-induced binding and neutralizing antibodies correlated with protective efficacy, suggesting immune correlates of protection. Taken together, this study demonstrates that the modular SpyTag/SpyCatcher functionalized HBsAg VLP platform induces potent immune responses and provides effective protection in macaques challenged with SARS-CoV-2, and sheds light on the broad range of applications of VLPs in vaccine development to address emerging viruses in a short timeframe. Overall, this project provides important preclinical insights into leveraging VLPs and the SpyTag/SpyCatcher system for SARS-CoV-2 prophylaxis and COVID-19 control.