It is now established that antigenic variation occurs in Plasmodiuminfections but,
unlike the African trypanosomes (T. brucei), the active region of the antigen is stable and
could possibly be blocked by vaccines. The antigen and the receptors on the immune cells
are closely linked. Phagocytic cells that take up the parasite antigens migrate to the
lymph nodes and become antigen-presenting cells.
The molecular structure of the antigens of the different phases of Plasmodiumhave
been analysed in detail. One of the characteristics of the antigens that has been deter-
mined is the fact that the major antigens are composed of repetitive sequences of amino-
acids. Some of the features with regard to malaria immunity that have been established
are:n The repetitive sequences that dominate the structure of the antigens are presented to
cells along T cell independent pathways.
n The parasite toxins which probably induce a cytokine response are thought to stimu-
late an innate non-specific (immune) mechanism which protects a non-immune per-
son during the first few weeks of an infection.
n Tumour necrosis factor (TNF), a pyrogenic substance induced by the malaria toxins,
appears to protect an individual against invasion by the parasites and at the same time
induces a ‘fever’ which may itself be protective.n 10.2 EFFECTOR MECHANISMS AGAINST THE
SPOROZOITE INVASION
The first infective stage of the parasite, the sporozoite, is inoculated into the blood-
stream by a mosquito feeding on the host’s blood. The sporozoite exits from the circu-
lating blood within 30 min and invades the liver parenchyma cells — the intrahepatocyte
stage.
Any form of protection must be able to react rapidly to prevent invasion of the liver
tissue. The antibodies and the activated immune cells (T cytotoxic cells) and the
cytokines have to be present in sufficient concentrations for a complete and effective
response.
The development of an anti-malaria vaccine must, like all vaccine production, centre
around obtaining and analysing the immunogenic antigens. Antigen extracted from the
sporozoite is known as the circumsporozoite antigen. The circumsporozoite protein
isolated from in vitro cultures has the following amino-acid sequence: asparagine —
alanine — asparagine — proline. These repeats are known as the (NANP)nsequence.
The synthetic production of the CS protein was the first attempt at producing a manu-
factured anti-malaria vaccine and has been extensively tested in laboratory infections
using rodents, primates and human volunteers. Some of the findings of those experiments
have shown that:n Some groups of inbred strains of mice produce antibodies.
n In Gambian volunteers an increase in T cells in response to circumsporozoite protein
was detected.In attempts to produce a protective antigen, some of the peptides that comprise the
circumsporozoite antigen have been synthesised to mimic the immunogenic molecules
of the antigen (the epitope). These synthetic compounds were then injected into mice
in order to develop a protective response. However, stimulation of the immune system
using the synthetic ‘antigens’ did not always occur. This was probably due to the fact thatPARASITOLOGY