There is evidence to show that subsequent generations of the parasite (after asexual
multiplication) have mechanisms to alter their antigenic configuration. The primary
antibodies, which take about 7–10 days to be produced, are then no longer effective.
Once the concentration of IFN-γincreases it may inhibit the development of the Th 2
cells needed for the antibody response.
n 10.6 ATTEMPTS TO DEVELOP ANTI-MALARIA VACCINES
The development and production of anti-malaria vaccine has been and still is the focus
of much research. The primary development has been based mainly upon the use of in
vitro and in vivo murine models. The problems associated with the development of
an anti-malaria vaccine are due to the fact that the parasite has various phases in its life-
history, such as the liver stage, the blood stage and the gametocytes. Apart from their
physiological and biochemical differences, each phase has a different antigenic profile
and the parasite appears to remain one step ahead of its host’s complex immune system.
The attempts to produce such a vaccine have followed two main strategies:
n To try and block the development of incoming parasites and prevent the development
of the hepatic (pre-erythrocytic) and the blood (erythrocytic) stages.
n To limit the development of existing parasites.
However, recently two additional types of malaria vaccine have been proposed:
n A vaccine that would either neutralise the factors responsible for the pathology, ie an
anti-disease vaccine.
n A vaccine that limits the transmission of malaria by immune interference with the par-
asite’s life-cycle, particularly the sexual development in the mosquito.n 10.6.1 VACCINATION WITH IRRADIATED SPOROZOITES
It has been proposed and attempted to protect humans by immunising them with atten-
uated sporozoites delivered by the bite of irradiated mosquitoes. A group of volunteers
were inoculated with sporozoites by multiple exposures to irradiated infected mos-
quitoes. Some individuals were apparently protected and were found to have high levels
of anti-sporozoite antibodies in their circulating serum. Their peripheral T cells were found
to respond to stimulation with a recombinant P. falciparumcircumsporozoite (CS) pro-
tein and hence they were considered to be sensitised to the infection.
The production of such a vaccine is only feasible in laboratories that have access to
mosquito-borne sporozoites. This problem can be partially solved by maintaining the sporo-
zoites in an in vitro culture. The sporozoites are then inoculated artificially into primates
and laboratory rodents, and such experiments have shown that antibodies are produced
against the infective stage — the sporozoite.
The antigenic region of the sporozoite, that is the immunogenic molecules stimulat-
ing an immune response, is known as the circumsporozoite (CS) protein (see section 10.2).
This antigenically active region (the epitope) contains proteins comprised of a series
of repeat amino-acids known as CS repeats. If a synthetic version of these molecules
could be vaccinated into the host, it could provoke an immune response that would then
attack an inoculated sporozoite and prevent the parasites from becoming established
within the host. The first attempts at preparing an anti-malaria vaccine incorporated the
synthetic CS amino-acid repeats, and the initial human vaccination trials involved two
preparations:
ASPECTS OF MALARIA