Novel vaccines and antiviral treatments for enterovirus induced infections and disease

Abstract

Enterovirus infections are common around the world and can impact people’s lives in various ways, causing pancreatitis, myocarditis, common cold and more. This thesis is focused on testing the effectiveness of new vaccines and an antiviral agent in the context of cystic fibrosis (CF) and type 1 diabetes (T1D).

Many enteroviruses cause respiratory infections. Due to their problematic lungs, patients with CF are extra susceptible to infections including those by viruses. In Paper I, we demonstrated that enteroviruses known as coxsackieviruses (CVB) are common in people with CF. We also showed that mice carrying the CF mutation most common in humans respond to a newly developed CVB vaccine by producing neutralising antibodies leading to protection against CVB infection. Poliovirus is another enterovirus and the inactivated poliovirus vaccine used in the Swedish national vaccination programme is similar to the new CVB vaccine. To understand how the CVB vaccine might work in people with CF, we measured neutralising antibodies against poliovirus in serum samples from patients. The results suggested that most individuals were able to establish robust immunity to poliovirus, indicating that the new CVB vaccine would provide similar immunity in the CF population.

Paper II and Paper III focused on vaccine responses and virus infections associated with T1D. It has been suggested that enteroviruses are involved in T1D development. Establishing vaccination coverage and antiviral treatments might therefore be beneficial for susceptible individuals. In Paper II, we showed that a CVB vaccine is safe and does not accelerate autoimmune disease in a diabetes prone host. Moreover, we demonstrated that the CVB vaccine protected mice from infection-induced acceleration of autoimmune diabetes. This and previous studies by the group, paved the way for a clinical trial with an equivalent vaccine, PRV-101. In Paper III we investigated the antiviral properties of Vemurafenib, a cancer drug, as potential antiviral treatment against enteroviruses. We showed that this drug prevents infection of cells at the primary site of infection (epithelial cells lining the gut), as wells as insulin-producing cells, demonstrating the potential for next generation anti-enterovirus treatments.

This thesis provides insight into the development of new vaccines and antiviral agents, mainly against CVBs with the goal of improving the lives of those affected by CF and preventing the development of T1D.