Experimental infection and protection against ... - TI Pharma

NF135.C10: a new Plasmodium falciparum clone for controlled human malaria
infections
Introduction
Malaria caused an estimated 216 million cases and around one million deaths in
2010 [1, 2], mainly in sub-Saharan Africa where most cases are caused by
Plasmodium falciparum (Pf). Development of vaccines and new drugs, and
better understanding of immunological processes are essential in order to tackle
this immense problem. Controlled Human Malaria Infection (CHMI), in which
healthy volunteers are exposed to bites of Pf-infected mosquitoes, is a powerful
tool to address questions regarding Pf drug and vaccine efficacy, clinical
properties, parasite kinetics and human immunology. Since the first CHMI by
mosquitoes fed on cultures of Pf [3], more than 1300 healthy volunteers have
been exposed to CHMI [4] with mainly either the Nijmegen Falciparum strain
NF54 [5] or its clone 3D7 [6]. Strain NF54 stably produces sexual stages required
for production of infectious mosquitoes. Parasites have been adapted to
laboratory conditions by continuous in vitro culture for more than three
decades. In the field, Pf isolates display a wide genetic diversity, which is
currently not represented by the available laboratory strains for CHMI. Other
strains, such as the South American 7G8 Pf clone [7, 8] of the Brazilian isolate
IMTM22 [9] have been sporadically used in limited number of volunteers [10-
12]. We therefore aimed to identify and test an additional Pf strain that can be
used in CHMIs, and developed several qualification criteria: i) The strain must
consistently produce gametocytes and sporozoites. ii) The strain should be
cloned to create a single genetically homogenous parasite population and
should be genetically characterized. iii) The clone should be sensitive to
commonly administered antimalarials. iv) It should be of non-African origin in
order to be geographically and genetically distinct from the NF54 strain, an
airport strain that probably originates from Africa [13, 14]. Here we report the
generation, characterization and first CHMI with NF135.C10, a new Cambodian
clone, including drug sensitivity, microsatellite profile, kinetics of parasitemia,
clinical features and immunological properties in a direct comparison with NF54.
Methods
Culturing of NF135.C10 and NF54 parasites
Parasites were cultured as described previously [15]. Briefly, NF135.C10 and
NF54 Pf asexual blood-stage parasites, regularly screened for mycoplasma
contamination, were grown in RPMI-1640 medium containing 10% human A +
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