Diagnosis, prevention and treatment of acute respiratory infections

Abstract

The dissertation focuses mainly on the prevention and treatment of the respiratory viruses SARS-CoV-2 and influenza, which cause a significant global disease burden. Patients who have undergone organ transplantation are at increased risk for severe infections and hospitalization, with COVID-19 being more severe than influenza. Prevention through vaccination is therefore crucial. However, our retrospective study shows that the flu vaccine has had low and variable effectiveness in this group over the past few years, highlighting the need for further prospective research and possibly adjusted vaccination strategies.

In a randomized study, we investigated whether intradermal vaccination with a lower dose of the mRNA-1273 vaccine (1/5 of the standard dose) provides sufficient protection. While the antibody response did not meet the pre-defined non-inferiority criteria, the response was substantial, with fewer systemic side effects. This dose-saving strategy could be valuable during pandemics, especially given the good booster response in individuals previously vaccinated with the lower dose, as shown in our follow-up study.

Another strategy, vaccination with microneedle patches, was safe but did not yield an effective immune response after a booster vaccination with the mRNA-1273 vaccine, likely because the nanoparticles were too large for skin diffusion.

Finally, we investigated ensovibep, a DARPin (designed ankyrin repeat protein) molecule that binds to the spike protein of SARS-CoV-2, preventing the virus from entering human cells. This treatment was shown to be safe for use in the early stages of COVID-19 in non-hospitalized patients.