Application of viral innate immune antagonists to improve vaccines

Utrecht University and MSD Animal health investigate new strategies to improve vaccine efficiency.

Vaccines, such as live attenuated pathogens, inactivated pathogens and subunit vaccines, are used to protect humans and animals from infectious diseases. Recently, versatile vaccine platforms have been generated to rapidly respond to newly emerging pathogens like the SARS-CoV-2. Among these platforms, many new vector vaccine technologies became available. These are safe by design but need improvements with regards to efficacy.

Upon introduction of mRNA vaccines in the target cells, the production of antigens is initiated as well as activation of several antiviral pathways including the integrated stress response. Viruses contain proteins to counteract this response and ensure efficient replication. This project aims to increase vaccine efficacy by coexpressing a viral stress antagonist together with the antigen.

In laboratory experiments, co-expressed viral stress antagonists boosted antigen expression compared to the same viral stress antagonist containing inactivating mutations (which served as a negative control). Based on these results, the vaccines were evaluated in vaccination experiments. Unfortunately, results from these experiments showed co-expression of a viral stress antagonist resulted in a lower immunity as observed with the antigen alone. further analysis showed that this is because the expression of a viral stress antagonist has a negative effect on antigen expression. A follow up of this project needs to focus on a vaccine vector that can equally express the antigen and VSA at high efficiencies.