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Experimental infection and protection against ... - TI Pharma

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130 Chapter 7<br />

Abstract<br />

The portfolio of Plasmodium falciparum (Pf) strains for controlled human<br />

malaria <strong>infection</strong>s (CHMI) primarily consists of NF54 <strong>and</strong> its clone 3D7.<br />

Availability of additional strains will allow better evaluation of efficacy of<br />

experimental vaccines <strong>and</strong> drugs, <strong>and</strong> underst<strong>and</strong>ing of immunological<br />

<strong>protection</strong> mechanisms.<br />

NF135 was isolated from a Dutch patients who acquired malaria whilst travelling<br />

in Cambodia. Parasites were adapted to continuous culture <strong>and</strong> cloned. Clone<br />

NF135.C10 consistently produced gametocytes <strong>and</strong> generated substantial<br />

numbers of sporozoites in Anopheles mosquitoes. NF135.C10 was tested in a<br />

CHMI trial in comparison with NF54 for parasitological, immunological <strong>and</strong><br />

clinical parameters. Two groups of five malaria-naive volunteers were exposed<br />

to bites of five NF54 or NF135.C10 infected mosquitoes.<br />

NF135.C10 parasites diverged from NF54 parasites by drug sensitivity <strong>and</strong><br />

genetic marker profiles. Both NF135.C10 <strong>and</strong> NF54 were infectious to humans.<br />

Three out of five volunteers challenged with NF135.C10 <strong>and</strong> four out of five<br />

challenged with NF54 developed parasitemia after seven to eleven days as<br />

detected by microscopy. The two strains showed great similarity in prepatent<br />

period, kinetics of parasitemia, clinical features <strong>and</strong> cellular immunological<br />

responses.<br />

In conclusion, we successfully established a new field strain of Pf that can be<br />

used in CHMI <strong>and</strong> vaccine studies.

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