PARASITOLOGY

(Tina Meador) #1

is usually part of the outer membrane (as in most protozoa) or the tegument (as in the
trematodes and cestodes) or the cuticle (as in the nematodes). Secretions from the para-
sites in the form of metabolic waste products or ‘enzymes’ are released to assist with
penetration and migration through tissues.
Once the epitope has been identified it has to be isolated, its molecular structure
ascertained and then synthesised. Recombination technology is now used to produce
synthetic antigens. After the compound proposed as a potential vaccine has been isolated,
synthesised and purified, a route of administration has to be determined. The two most
common methods are oral and/or through the skin.
The objective in producing an immunogenic antigen is to sensitise the host to a par-
ticular pathogen. The antigen stimulates the disease conditions but at much reduced or
attenuated level. The adaptive immune system is stimulated and the eventual outcome
is that the body will now have circulating primed B memory and T memory cells.


n 9.2 THE DEVELOPMENT OF A POTENTIAL VACCINE
The essential ingredient to initiate the development of an anti-parasite vaccine is a plenti-
ful supply of live parasite material in order to isolate the immunogenic antigen. If it is
possible the target infection, ie the parasite, should be established in a laboratory host.
The ideal situation would be to maintain the complete life-cycle of the parasite in a lab-
oratory host/hosts, ie an in vivoculture of the parasite. If the above is not possible there
are alternatives such as maintaining one stage of the life-cycle in vivo, using a laboratory
host, and the other stages or phases of the life-cycle maintained in an in vitro culture.
The asexual multiplicative phases of both protozoan and helminth parasites can often
be adapted to surviving in vitro. A most important aspect is to maintain the stage of the
parasite that is infective to mammalian hosts.
One of the many problems in the manufacture of a vaccine is the fact that most para-
sites have more than one antigenic identity. In addition some are capable of changing their
antigenicity in response to the host’s immune reaction.
A vaccine must be able to prevent the parasite from becoming established within the
host. In order to achieve that objective, it is imperative to try and understand the host’s
normal/natural immune response.
One the most studied helminth parasites, with particular emphasis on immunity, is the
digenean trematode Schistosoma mansoni. The complete life-cycle can maintained under
laboratory conditions. The snail intermediate host Biomphalaria glabratasurvives well in
aquaria and the adult stages live for relatively long periods in most strains of laboratory
mice. The S. mansonimodel infection has demonstrated that certain degrees of immunity
can be achieved by the presence of a living infection. The live parasite is protected
against the immune response which it has stimulated by acquiring host proteins onto its
tegument. These host proteins confuse the immune system into treating the parasite as
host material. In other words acquired molecules which disguise the parasites provide a
form of molecular disguise. This either prevents a secondary infection while keeping the
primary infection under control and/or modulates the effect of the parasite upon the host,
ie it immunomodulates the disease. The latter can have the effect of reducing the patho-
logical effect of the parasite (see section 7.5.5).
For a discussion on the development of an anti-malarial vaccine see section 10.6.


n 9.2.1 ADJUVANTS
In order to be certain of stimulating the immune response when the potential immunogenic
antigen is weak, an adjuvant is used. An adjuvant is a substance that non-specifically


VACCINES
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