ASPECTS OF MALARIAn 10.6.4 MEROZOITE STAGE VACCINES
The ‘signet ring’ trophozoite stage develops within the erythrocytes into schizonts and,
after they undergo the process of schizogony, they release blood stage merozoites cap-
able of invading new red blood cells. Newly formed P. falciparummerozoites have been
isolated and from these merozoites surface polypeptide antigens have been extracted, known
as the merozoite surface antigen-1 (MSA-1) and merozoite surface antigen-2 (MSA-2).
Both MSA-1 and MSA-2, like the circumsporozoite proteins, have also been tested as a
potential anti-malaria vaccine. Aotusmonkeys (howler monkeys) vaccinated with purified
P. falciparumMSA-1 like material induced protection against being infected under labo-
ratory conditions with infected P. falciparumerythrocytes. Using the same type of tech-
nology, a similar vaccine from the merozoites of P. vivaxhas been prepared for testing.
This merozoite surface antigen MSA-2 varies in size (45 and 55 kDa) and contains a
highly diverse central region of approximately 160 amino-acids. In order to use it as a
vaccine it has to be conjugated to a Diphtheriatoxoid. T helper cell responses in mice were
induced by the MSA-2 proteins.
n 10.7 A SYNTHETIC VACCINE
In order to overcome the problems of having to isolate antigens from the various stages,
a synthetic polymeric blood stage vaccine was produced, called SPF 66. It contains three
short peptides representing sequences from three P. falciparumblood stage antigens
and was prepared and tested in Colombia on volunteers. The vaccine was composed of
peptides SPF 35.1 and SPF 55.1, based on partial sequences obtained from two as yet
unidentified P. falciparummolecules. The first test results showed the SPF 66 vaccine to
be immunogenic and safe to use in humans. A further set of trials was carried out on another
352 volunteers. The immunisation schedule was 2 mg doses of SPF 66 in alum at days
0, 30, 180. Unfortunately the results of the trials did not establish SPF 66 as a potential
vaccine. The effects of SPF 66 vaccine on P. falciparuminfections were that two of the
peptides (in the vaccine) bound to erythrocytes and inhibited invasion of a number of
erythrocytes.
Although there have been great advances in the understanding of the immune response
to the malaria parasite, a vaccine to protect against being infected is still not available.
n SUMMARY
There are four species of Plasmodiumthat are the cause of human malaria, which is one
of the main causes of child deaths in large areas of the world. The intracellular habitat of
Plasmodiumhelps to protect it from destruction by the host’s immune response. Each phase
of the parasite, ie the sporozoite, the merozoite and the gamont have a different antigenicity,
with each inducing a host response. The effector mechanisms against all of the different
stages have been studied in detail, mainly by the examination of serum from infected patients.
There is an ongoing programme to try and produce a vaccine against Plasmodium, using
all of the antigenic stages of the parasite.End of chapter questions
Question 10.1 What parasites are responsible for the disease malaria?
Question 10.2 What are possible causes of the symptoms associated with malaria?