Experimental infection and protection against ... - TI Pharma

152 Chapter 8
Abstract
Vaccines and new drugs are needed to prevent the approximately one million
deaths and hundreds of millions of cases caused by Plasmodium falciparum (Pf)
malaria annually. To test these vaccines and drugs, volunteers are infected by
the bites of Pf sporozoite (SPZ)-infected mosquitoes under controlled conditions.
Such infections are limited to the few centres with production of PfSPZ-infected
mosquitoes. We assessed the capacity to infect volunteers by intradermal (ID)
injection of aseptic, purified, vialed, cryopreserved PfSPZ (PfSPZ Challenge).
Dutch volunteers received ID injections of PfSPZ that had been cryopreserved
for 27-30 months. In a dose escalation study volunteers (N=6/group) received
2,500, 10,000, or 25,000 PfSPZ. Detection of blood-stage parasites by
microscopy was the primary outcome. Kinetics of parasitemia were
retrospectively assessed by quantitative PCR. Fifteen of eighteen volunteers
(84%) developed Pf parasitemia, 5/6 volunteers at each dose. Infection was safe.
There were no differences between groups in time until parasitemia by
microscopy and PCR, parasite kinetics, clinical symptoms and signs or laboratory
values.
Aseptic, purified, vialed, cryopreserved PfSPZ manufactured in compliance with
regulatory standards and administered ID successfully infected volunteers.
Following optimization of administration, such PfSPZ could be used to assess
efficacy of vaccines and drugs in clinical trial centres worldwide. In addition
PfSPZ Challenge can also be used for immunization strategies against malaria.
For example, 100% protection against Pf infection in volunteers immunized by
exposure to PfSPZ-infected mosquitoes while taking chloroquine was recently
demonstrated. PfSPZ Challenge could be used to translate this artificial
immunization protocol into an implementable vaccine.