Experimental infection and protection against ... - TI Pharma

General Discussion 225
and between regions [82]. Genetic diversity of the parasite strains is a major
challenge for vaccines that target strain-specific antigens, of which the vaccine
candidate AMA1 is one example, and puts limitations on the direct translation of
results from experimental infections into the field situation. The availability of a
small portfolio of genetically well-characterized Pf strains for controlled malaria
infections would be a major asset. We have taken the first step towards a field
strain infection model by showing that NF135, a field strain from Cambodia is
infectious to humans (Chapter 7). Future studies will need to establish whether
the infectivity of NF135 is comparable to NF54 and the dose that should be
administered to achieve 100% infection rates. Once several field strains are
available, the controlled infection of different groups of volunteers with
heterologous strain parasites would be highly instrumental to investigate the
promiscuity of responses induced particularly with diversity covering vaccines or
whole-parasite vaccine strategies.
A final potential limitation of controlled malaria infection models relates to the
uncontrolled number of sporozoites inoculated by biting mosquitoes. This
number is generally thought to vary between 100-300 sporozoites per bite up to
a maximum of several thousand sporozoites [83-86]. Use of a well-defined
number of inoculated sporozoites will strengthen the power of the model
(Chapter 6). In principle, the most accurate way of dosing sporozoites is to inject
them directly by needle and syringe, as the number of sporozoites counted in
mosquito salivary glands or the number of mosquito bites is a poor predictor of
the number of sporozoites injected [84]
Whole-sporozoite inoculation
The concept of inoculation of whole sporozoites into humans is not novel. The
first reports can be found in 1926, when five patients were injected with P. vivax
in order to test antimalarial drugs [87]. More frequent records are found
between 1937 and 1963 when malariatherapy was given to neurosyphilis
patients, mostly by bites of infected mosquitoes but also by sporozoite injection
[88, 89]. Infection of patients with P. falciparum or P. vivax sporozoites was
primarily by intravenous route of freshly extracted sporozoites, since the
viability was known to heavily depend on storage time, condition and handling
[88]. Intradermal injection of sporozoites to investigate its relationship with
prepatent period or clinical outcome were variably successful, mostly because of
the unstable infection rates [90, 91]. Techniques to freeze and thaw sporozoites