Antiviral Immunity and New Vaccines For Early Intervention and Prevention of Lung Disease In CF

Bakgrund:

Respiratory virus infections increase the sensitivity of the Cystic Fibrosis (CF) lung to bacterial colonization and is the major cause of pulmonary exacerbations in CF. Exacerbations cause a gradual loss of lung function leading to terminal lung disease. Therefore, prevention of common viral infections is likely to provide significant benefits in lung function for individuals with CF.

Enteroviruses, including the rhinoviruses, echo- and Coxsackie B viruses (CVB) are frequently detected in CF, especially after experiencing pulmonary exacerbations. We have recently presented high safety and immunogenicity of new mono- and multivalent CVB vaccines in pre-clinical studies. This type of vaccine is now under development for testing in clinical trials. If it proves to be effective in pre-clinical models of CF, it may also be considered for individuals with the disease.

CF is associated with many changes in immune functions which could potentially affect the ability to respond to vaccination. Målsättning:

Here, we hypothesize that CVB infections are common in CF and can be prevented by prophylactic vaccination. The first aim is to document how common CVB infections are in CF. In the second aim we test the hypothesis that the CVB vaccines are immunogenic in an experimental model of CF and that vaccination provide strong protection from virus infection.

In the third aim we will perform studies estimating how well individuals would respond to a CVB vaccine. We hypothesize that this can be achieved by examining the immunity to poliovirus in the CF population. All individuals living in Sweden are vaccinated with the inactivated poliovirus vaccine, which is produced in a similar manner as the new CVB vaccines.

Arbetsplan:

The prevalence of CVB infections in CF and healthy controls will be assessed by serological studies. If the new CVB vaccines are immunogenic and can prevent infections in CF will be addressed using an experimental model for CF carrying the most common mutation in CFTR (delF508). Neutralizing antibodies to polio 1 and 3 will be measured in serum samples from individuals with CF and healthy controls and provide a robust estimate of how well individuals with CF would respond to a CVB vaccine.

Betydelse:

Collectively, the results to be gained from these studies may support the potential of a vaccination strategy employing a CVB vaccine as a complementary treatment for the prevention of virus induced pulmonary exacerbations in CF.