Leiden University Scholarly Publications

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Duszenko, N. (2024)

A supramolecular chemistry approach for potentiating live attenuated whole-organism vaccines

Doctoral Thesis
Malaria continues to wreak havoc in tropical regions, due largely to the lack of an effective vaccine. Vaccine candidates based on whole parasites have shown promising results in malaria-naïve individuals, but their potency in malaria-exposed individuals is considerably lower. This dissertation described the development of a chemical strategy for boosting such parasites’ potency in pursuit of more efficacious malaria vaccines for use in endemic areas.
Chapter 2 outlined the adaptation of a method for chemically modifying microbial cell surfaces.
Chapter 3 showed the chemistry underlying this modification system to be stably compatible with in vivo usage.
Chapter 4 demonstrated that when the chemical modification system was used to introduce immune-potentiating agents onto bacteria, better immune responses ensued.
Chapter 5 tied it all together by using the chemical modification system to potentiate malaria parasites, and showed that doing so markedly improved immune...Show moreMalaria continues to wreak havoc in tropical regions, due largely to the lack of an effective vaccine. Vaccine candidates based on whole parasites have shown promising results in malaria-naïve individuals, but their potency in malaria-exposed individuals is considerably lower. This dissertation described the development of a chemical strategy for boosting such parasites’ potency in pursuit of more efficacious malaria vaccines for use in endemic areas.
Chapter 2 outlined the adaptation of a method for chemically modifying microbial cell surfaces.
Chapter 3 showed the chemistry underlying this modification system to be stably compatible with in vivo usage.
Chapter 4 demonstrated that when the chemical modification system was used to introduce immune-potentiating agents onto bacteria, better immune responses ensued.
Chapter 5 tied it all together by using the chemical modification system to potentiate malaria parasites, and showed that doing so markedly improved immune responses in an in vivo immunization model.
Chapter 6 summarized these findings in the context of malaria vaccine development and posited next steps forward.
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Malaria
Infectious disease
Vaccine
Supramolecular chemistry
Adjuvant
All authors
Duszenko, N.
Supervisor
Roestenberg, M.; Leeuwen, F.W.B. van
Committee
Visser, L.G.; Buckle, T.; Velders, A.H.; McCalll, M.M.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2024-05-16