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Towards a blood stage malaria vaccine, dealing with allelic polymorphism in the vaccine candidate apical membrane antihen 1

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Towards a blood stage malaria vaccine, dealing with allelic

polymorphism in the vaccine candidate apical membrane antihen 1

Kusi, K.A.

Citation

Kusi, K. A. (2012, January 18). Towards a blood stage malaria vaccine, dealing with allelic polymorphism in the vaccine candidate apical membrane antihen 1. Retrieved from

https://hdl.handle.net/1887/18387

Version: Corrected Publisher’s Version

License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden

Downloaded from: https://hdl.handle.net/1887/18387

Note: To cite this publication please use the final published version (if applicable).

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Towards a blood stage malaria vaccine; dealing with allelic polymorphism in the vaccine

candidate apical membrane antigen 1

Proefschrift

ter verkrijging van de graad van

Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof.mr. P.F. van der Heijden, volgens besluit van het College voor Promoties te

verdedigen op woensdag 18 januari 2012 klokke 15:00 uur

door

Kwadwo Asamoah Kusi

geboren te Accra, Ghana in 1977

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Promotie commissie

Promotor Prof.dr. A.M. Deelder

Co-promotor Dr. C.H.M. Kocken, BPRC, Rijswijk

Co-promotor Dr. E.J. Remarque, BPRC, Rijswijk

Overige leden Prof. dr. R.W. Sauerwein, UMC St. Radboud, Nijmegen Dr. D. Dodoo, NMIMR, Ghana.

Prof.dr. R.R.P. de Vries Prof.dr. T.H.M. Ottenhoff Prof.dr. M. Yazdanbakhsh

The studies described in this thesis were performed at the Biomedical Primate Research Centre (BPRC) in Rijswijk, the Netherlands, with funds from EMVI, EMVDA and EUROMALVAC. The author was also supported financially by a GETFund scholarship (Ghana).

Printing of this thesis was with financial support from the GETFund, BPRC and BioGenes GmbH, Berlin.

Cover design: Henk van Westbroek

Printing: Off Page

ISBN: 978-94-6182-050-1

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To Stella, the love of my life

and to Cheryl, the shining star in my life

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Table of contents

Chapter 1 General introduction 1

Chapter 2 Humoral immune response to mixed PfAMA1 alleles; 27 multivalent PfAMA1 vaccines induce broad specificity.

Chapter 3 Generation of humoral immune responses to multi-allele 53 PfAMA1 vaccines; effect of adjuvant and number of

component alleles on the breadth of response.

Chapter 4 Immunisation with different PfAMA1 alleles in 77

sequence induces clonal imprint humoral responses that are similar to responses induced by the same alleles as a vaccine cocktail in rabbits. Chapter 5 Safety and immunogenicity of multi-antigen AMA1- 95

based vaccines formulated with CoVaccine HT™ and Montanide ISA 51 in rhesus macaques. Chapter 6 Measurement of the plasma levels of antibodies 115

against the polymorphic vaccine candidate apical membrane antigen 1 in a malaria-exposed population. Chapter 7 General discussion 131

Summary/Nederlandse samenvatting 143

List of publications 151

Acknowledgements 153

Curriculum vitae 155

Supplementary figures 157

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