Experimental infection and protection against ... - TI Pharma

NF135.C10: a new Plasmodium falciparum clone for controlled human malaria
infections
Pf135.C10 re-stimulation. Notably, responses to heterologous re-stimulation
were very similar to homologous responses, both in kinetics and magnitude.
Considerable genetic diversity has been found in a number of important malaria
antigens and vaccine candidates, especially in blood stages [38], but also in preerythrocytic
stages [39]. Specific (conserved) antigens may be responsible for
induction and maintenance of heterologous memory responses against Pf [40,
41]; conserved epitopes have indeed been found in many immunogenic proteins
[42-44], although some being cryptic and therefore not available for the immune
system [45]. Albeit tested in only a small number of volunteers, (partial)
protection has previously been reported after heterologous challenge infection
following immunisation with radiation-attenuated sporozoites [10, 46, 47] or a
previous experimental infection [48]. Whether the heterologous T-lymphocyte
responses observed in our volunteers also translate into or represent crossstrain
protective immunity in vivo remains to be investigated.
The availability of NF135.C10 increases the portfolio of Pf parasites that can be
used in CHMI. Obtaining additional multiple genetically distinct, fully
characterized and sequenced Pf clones will be important in the evaluation
process of diversity covering sub-unit vaccines or whole-parasite based vaccine
approaches [4], intended to protect against all Pf parasite strains in nature [49].
Additionally, if immunization with whole sporozoite vaccines based on one
single Pf strain does not fully protect against CHMI with heterologous Pf
parasites, it will be necessary to determine whether immunization with
sporozoites from a combination of clones are required to achieve such
protection. Finally, to take advantage of our recent demonstration that CHMIs
can also be successfully conducted by needle and syringe inoculation of aseptic,
purified, cryopreserved Pf sporozoites called PfSPZ Challenge (Roestenberg et
al., submitted), we have established the master and working cell banks, and
manufacturing process required to produce PfSPZ Challenge using NF135.C10
parasites (Sim et al., unpublished).
In conclusion, increasing the portfolio of new Pf parasite strains, as achieved
here for NF135.C10, will accelerate the evaluation of malaria vaccines
candidates by facilitating the downstream selection process for further clinical
vaccine development. Although more trials will be necessary to fine-tune the
heterologous CHMI model with strain NF135.C10, the current results will boost
the continued application of CHMIs as a crucial tool for malaria vaccine
development.
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