Experimental infection and protection against ... - TI Pharma

164 Chapter 8
was safe and well tolerated, but immunogenicity and protective efficacy were
not nearly to the levels found after mosquito bite immunization [28]. The data
reported herein on PfSPZ Challenge administered ID demonstrated that the
manufacturing process produces viable and potent SPZ. These data, along with
non-human primate immunization studies with PfSPZ Vaccine, informed the
design of the next clinical trial of the PfSPZ Vaccine, which is being administered
by intravenous injection [28].
Another approach to whole SPZ vaccination was recently established [21-22].
Healthy malaria-naïve volunteers were protected for 28 months against CHMI
after being immunized by exposure to bites of PfSPZ-infected mosquitoes while
taking the antimalarial drug chloroquine. This protection was induced using >
20-fold fewer PfSPZ-infected mosquitoes [36 to 45] than needed for protection
with radiation attenuated PfSPZ (> 1000) [21-22]. PfSPZ Challenge can replace
mosquito bites, allowing for rapid translation of this experimental research
finding into a potential vaccine. We are planning the first clinical trials of PfSPZ
Challenge administered to volunteers taking chloroquine for 2012.
In summary, we have established that aseptic, purified, vialed, cryopreserved
PfSPZ (PfSPZ Challenge) are infectious to humans for at least 2.5 years after
cryopreservation. These data provide the rationale and foundation for a clinical
trials program aimed at significantly increasing the scale of CHMI in clinical trials
of malaria vaccines and new drugs, and producing, testing, and licensing a highly
effective, long-acting PfSPZ malaria vaccine.
Acknowledgements
We thank the trial volunteers, the staff from the Clinical Research Centre
Nijmegen and the staff from the RUNMC Pharmacy who made this study
possible; Wendy Arts, Nanny Huiberts, Chantal Siebes, Marlou Kooreman, Paul
Daemen and Ella Driessen for reading many thick smears; and Dr. Gheorghe Pop
for his cardiac monitoring of the trial volunteers. We thank Bas van Haren for his
support with the ADAMTS13 measurements and Jody van den Ouweland for the
performance of the Troponin T measurements. We thank the members of the
Safety Monitoring Committee, Dr. Barney Graham, Dr. David Diemert and Dr.
Alexander Rennings for their participation and for their guidance and safety
recommendations throughout the trial. We thank the entire Sanaria
Manufacturing Team including Gametocyte Production: Yonas Abebe, Asha Patil,
Yeab Getachew, Mark Loyvesky, Bingbing Deng; Mosquito Production: Steve