Capsid-like particles decorated with the SARS-CoV-2 receptor-binding domain elicit strong virus neutralization activity

The rapid development of a SARS-CoV-2 vaccine is a global priority. Here, we develop two capsid-like particle (CLP)-based vaccines displaying the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. RBD antigens are displayed on AP205 CLPs through a split-protein Tag/Catcher, ensuring unidirectional and high-density display of RBD. Both soluble recombinant RBD and RBD displayed on CLPs bind the ACE2 receptor with nanomolar affinity. Mice are vaccinated with soluble RBD or CLP-displayed RBD, formulated in Squalene-Water-Emulsion. The RBD-CLP vaccines induce higher levels of serum anti-spike antibodies than the soluble RBD vaccines. Remarkably, one injection with our lead RBD-CLP vaccine in mice elicits virus neutralization antibody titers comparable to those found in patients that had recovered from COVID-19. Following booster vaccinations, the virus neutralization titers exceed those measured after natural infection, at serum dilutions above 1:10,000. Thus, the RBD-CLP vaccine is a highly promising candidate for preventing COVID-19.Molecular basis of virus replication, viral pathogenesis and antiviral strategie

Lack of immunological DNA sensing in hepatocytes facilitates hepatitis B virus infection.

Hepatitis B virus (HBV) is a major human pathogen and about one third of the global population will be exposed to the virus in their life time. HBV infects hepatocytes where it replicates its DNA and infection can lead to acute and chronic hepatitis with high risk of liver cirrhosis and hepatocellular carcinoma. Despite this, there is limited understanding of how HBV establishes chronic infections. In recent years it has emerged that foreign DNA potently stimulates the innate immune response, particularly type I IFN production, and this occurs through a pathway dependent on the DNA sensor cGAS and the downstream adaptor protein STING. In this work we describe that human and murine hepatocytes do not express STING. Consequently, hepatocytes do not produce type I IFN in response to foreign DNA or HBV infection and mice lacking STING or cGAS exhibit unaltered ability to control infection in an adenovirus-HBV model. Stimulation of IFN production in the murine liver by administration of synthetic RNA decreases virus infection, thus demonstrating that IFN possess anti-HBV activity in the liver. Importantly, introduction of STING expression specifically in hepatocytes reconstitutes the DNA sensing pathway, which leads to improved control of HBV in vivo. In conclusion, the lack of a functional innate DNA sensing pathway in hepatocytes hampers efficient innate control of HBV infection. This may explain why HBV has adapted to specifically replicate in hepatocytes, and could contribute to the weak capacity of this cell type to clear HBV infection