Experimental infection and protection against ... - TI Pharma

Long-term protection against malaria after experimental sporozoite inoculation 207
Discussion
Here we report for the first time the persistence of immunity in human
volunteers to re-infection with Plasmodium falciparum more than two years
after previous exposure. Using a recently developed artificial immunisation
protocol [9] we observed long lasting protection in four of six re-challenged
volunteers and markedly delayed patency in the two remaining volunteers. In
addition, we describe the maintenance of Pf-specific T cell IFNγ responses.
The notion that immunity to malaria is short-lived derives primarily from
anecdotal reports of returning semi-immune immigrants. A critical review of the
literature, however, reveals that such migrants appear to retain some
protection, albeit only from severe disease and death [19]. The induction and
persistence of clinical and parasitological immunity is more controversial, due to
the great diversity in malaria transmission intensity, age, genetic background
and study endpoints, complicating interpretation [4]. Protective immunity to
clinical malaria can be acquired relatively rapidly [4], and in settings of epidemic
malaria, some measure of clinical protection may be sustained over several
years [20]. However, meta-analyses of intermittent preventive treatment studies
in naturally exposed infants and children show renewed susceptibility following
discontinuation of the intervention [21] and a historical review of patients
treated for neurosyphilis by (repeated) artificial malaria infection revealed no
sterile protective immunity against subsequent re-challenge [22]. Moreover,
protection induced in volunteers by irradiated sporozoite inoculation lasted 42
weeks in only a few subjects [5] and the protection induced by the most
successful sub-unit vaccine to date, RTS,S, seems to wane [6]. In summary,
naturally acquired immunity is far from optimal, but protective immunity to
severe disease can be maintained [4,19,23].
The long-term protection against malaria in this study is thus surprising when
compared with naturally acquired immunity. Several factors may account for
this discrepancy. Firstly, the same Pf strain was used for both the immunisation
protocol and the experimental challenges. Well-described target antigens for
protective immunity exhibit high rates of genetic variation, circumventing crossprotective
immunity in the field [24]. Secondly, our immunisation protocol
prevents high blood-stage parasitemia, whilst repeated parasitemia in endemic
areas is thought to suppress the development of immunity [25]. Thirdly, we
immunised adult individuals, whereas natural exposure is first encountered by
the immature immune system of infants4 or even in utero [26]. Finally, the