Experimental infection and protection against ... - TI Pharma

Long-term protection against malaria after experimental sporozoite inoculation 209
but without overt clinical thrombotic microangiopathy or bleeding
complications. In addition we report incidental decreases of von Willebrand
cleaving protease, possibly as a result of increased consumption of the protease
[30]. This is consistent with previous data concerning von Willebrand factor
activation in experimental malaria [13]. The clinical relevance of these findings
and their relation with the cardiac event is as yet unclear.
Our relatively simple immunisation protocol represents a blueprint for induction
of sustained anti-malarial immunity, providing a novel tool for exploring
mechanisms of immunity and highlighting new research priorities. Precedence
must be given to basic understanding of mechanisms of protection in this study
and those factors which inhibit protection in naturally-exposed populations.
Furthermore, strain specificity can be investigated with the use of heterologous
challenge infections and in field studies. Given the efficacy of our immunisation
protocol, however, equal emphasis on a pragmatic parallel approach to develop
an implementable whole-organism-based vaccine is justified.
In conclusion, the irrefutable evidence that long-term immunity against malaria
is possible holds a promise for an urgently needed malaria vaccine.
Acknowledgements
This trial was financed by a grant from the Dioraphte foundation. ACT is funded
by the European Malaria Vaccine Development Association, MBBM was
supported by an European Union FP6 Network of Excellence (BioMalPar)
fellowship, KNM was funded by a Mozaiek grant from the Netherlands
Organisation for Scientific Research. We thank the trial volunteers and the staff
from the Clinical Research Centre Nijmegen who made this study possible. We
thank the following individuals for their assistance during the trial: Laura Pelser,
Jolanda Klaassen, Astrid Pouwelsen, Jacqueline Kuhnen for the mosquito
infection and dissection work, Wendy Arts, Nanny Huiberts, Chantal Siebes,
Marlou Kooreman, Paul Daemen and Ella Driessen for reading many thick
smears. We would also like to acknowledge the contributions of Alexander
Rennings for his help with monitoring volunteer safety and the cardiologists
Gheorghe Pop and Marc Brouwer for their dedication to the cardiac monitoring
of the trial volunteers. We acknowledge the work of Richard Huijbens for the