Leiden University Scholarly Publications

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Schats, R. (2019)

Safety and efficacy after immunization with Plasmodium falciparum sporozoites in the controlled human malaria infection model

Doctoral Thesis
Using a variety of anti-malaria tools has resulted in a steady decline of malaria in several endemic countries worldwide. An effective vaccine will be critical to halt malaria or even succeed to final eradication. In that perspective, we studied the potential of whole sporozoite immunization by bites of P. falciparum infected mosquitoes under chemoprophylaxis (CPS). In this thesis we further explored this CPS model and assessed different immunizing doses, type of chemoprophylaxis and immunological determinants of disease and protection. We found a clear dose dependent efficacy, independent of type of chemoprophylaxis, found CD107a and CD8 T cells producing granzyme B related to protective immunity. In the field many genetically different strains circulate and a future vaccine should be able to cover multiple strains. We re-challenged volunteers with a different strain and found modest heterologously protection.
We retrospectively assessed the parasitological dynamics and...Show more

Using a variety of anti-malaria tools has resulted in a steady decline of malaria in several endemic countries worldwide. An effective vaccine will be critical to halt malaria or even succeed to final eradication. In that perspective, we studied the potential of whole sporozoite immunization by bites of P. falciparum infected mosquitoes under chemoprophylaxis (CPS). In this thesis we further explored this CPS model and assessed different immunizing doses, type of chemoprophylaxis and immunological determinants of disease and protection. We found a clear dose dependent efficacy, independent of type of chemoprophylaxis, found CD107a and CD8 T cells producing granzyme B related to protective immunity. In the field many genetically different strains circulate and a future vaccine should be able to cover multiple strains. We re-challenged volunteers with a different strain and found modest heterologously protection.
We retrospectively assessed the parasitological dynamics and adverse events using a positive qPCR rather than thick smear and found reduced the clinical symptoms of malaria for volunteers after challenge.
Successful malaria eradication will be more likely to be achieved with a multi-disciplinary approach. Additionally, sufficient and continuous funds will proof to be of tremendous necessity.

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Malaria
Human controlled infection model
Vaccination
Plasmodium falciparum
Heterologous
Protection
Immunization
All authors
Schats, R.
Supervisor
Visser, L.G.; Sauerwein, R.W.
Committee
Yazdanbakhsh, M.; Ottenhoff, T.H.M.; Ven, A.J.A.M. van der; Genderen, P.J.J. van
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2019-11-12
ISBN (print)
9789463238854

Funding

Sponsorship
Financial support: The Netherlands Organisation for Health Research and Development, Dioraphte foundation, the European Union Seventh Framework Programme (EviMalar), Top Institute Pharma. Individual grants or fellowships were received from European Malaria Vaccine Development Association (EMVDA), the Bill and Melinda Gates Foundation and European Malaria Vaccine Development Association (EMVDA) fellowship.