Experimental infection and protection against ... - TI Pharma

196 Chapter 10
Pre-erythrocytic stage
Sporozoites
Liver
Blood stage
Chloroquine
mediated
killing
Merosome
Merozoites
individuals [5]. Recently we described a novel methodology for induction of
immunity to Pf in humans, based on an immunisation procedure involving the
repeated exposure to infectious mosquito bites under chloroquine prophylaxis
[9]. Using this method, clinical disease was prevented by the drug that kills
asexual blood-stage parasites, but allows complete liver-stage parasite
development (Figure 1). Volunteers were protected from an experimental
challenge with the homologous parasite strain two months later. Protected
volunteers developed only low-level parasite-specific antibody activity, but
strong parasite-specific effector memory T cell responses, characterized by the
production of IFNγ and IL-2 after stimulation in vitro.
The objective of the current follow-up study was to assess the persistence of
protection against Pf infection after experimental immunisation. We rechallenged
volunteers by the bites of sporozoite-infected mosquitoes after a
period of 2.5 years.
Skin
Erythrocytes
Lymph node
Figure 1. Course of Plasmodium falciparum parasite development under
chloroquine prophylaxis. Sporozoites are injected into the skin by an infected
female Anopheles sp. mosquito. A proportion migrates through the bloodstream
to the liver. Parasites develop and multiply in hepatocytes over a period of 6-7
days. Subsequently, merosomes bud from infected hepatocytes into the sinusoid
and the released merozoites invade red blood cells for further asexual
multiplication. Chloroquine prophylaxis only targets and prevents replication of
parasites in red blood cells, thereby allowing the induction of immune responses
against preceding stages.