Leiden University Scholarly Publications

Persistent URL of this record https://hdl.handle.net/1887/4284805

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Prins, M.L.M. (2025)

Diagnosis, prevention and treatment of acute respiratory infections

Doctoral Thesis
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...Show moreThe 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.
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Influenza vaccine effectiveness
Solid organ transplant patients
Intradermal vaccination
Nanoporous ceramic skin patch
mRNA-1273 vaccine
Ensovibep
SARS-CoV-2
Influenza
All authors
Prins, M.L.M.
Supervisor
Visser, L.G.
Co-supervisor
Groeneveld, G.H.; Roukens, A.H.E.
Committee
Cannegieter, S.C.; Vossen, A.C.T.M.; Bemelman, F.; Bruijning, P.C.J.; Sanders, R.W.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2025-12-11
ISBN (print)
9789465109190
DOI
doi:10.60602/1887/4284805

Funding

Sponsorship
Chipsoft, ABN Amro; Research Manager; Congress Care; Wetenschapsfonds Hagaziekenhuis; Generations Sound/Light/Video.