enhances the immune response and is administered in combination with the vaccine.
Adjuvants are often used when the antigen has a low immunogenicity or the amount of
antigen available is restricted.
Adjuvants appear to act in the following ways: by prolonging the antigen within the
host; enhancing the co-stimulatory signals; and finally stimulating non-specific lympho-
cyte proliferation.
The following compounds are among the most commonly used adjuvants:
n Aluminium potassium sulphate (alum), a salt that when mixed with the antigen pre-
cipitates the antigen and results in a slower release of antigen. This effectively
increases the size of the antigen.
n Freund’s incomplete adjuvant is made up of antigen in aqueous solution, with mineral
oil and an emulsifying agent. The oil surrounding the antigen is dispersed in small
quantities (droplets) and the antigen is released slowly from the site of inoculation.
n Freund’s complete adjuvant in addition to the water-oil mixture contains a heat-killed
bacterium Mycobacteria. The mycobacterial cell wall plus the muramyl dipetide com-
ponent of the mycobacterial cell wall activates phagocytic cells and is more potent than
the incomplete Freund’s adjuvant.
n An established preparation often used an adjuvant is BCG (Bacille Calmette–Guérin),
widely used as an immunising agent against tuberculosis. BCG contains an attenuated
strain of Mycobacterium bovisand is also used an immunopotentiator with Mycobacterium
lepraeas an anti-leprosy vaccine.
In the process of developing specific acquired immunity to mycobacterial antigens, BCG
vaccination induces an altered immune reactivity to heterologous antigens and hence is
also widely used under experimental conditions as an adjuvant.
The immunity that is achieved in vaccinated subjects by using BCG is due to a specific
anti-mycobacterial cell-mediated immune (CMI) response. The cell-mediated immune
response after the BCG injection is due to the following affects: the activation of
macrophages mediated by CD4+T cells; the subsequent proliferation of CD8+T cells;
and the development of a granuloma.
The effects of using an adjuvant are an increased non-specific resistance against unre-
lated pathogens. Potentiated humoral and CMI responses to antigens are associated with
or conjugated to non- or poorly immunogenic molecules. BCG has been shown to stimu-
late DNA synthesis in draining lymphoid tissues.
n 9.2.2 FACTORS THAT INFLUENCE THE DEVELOPMENT OF
IMMUNE RESPONSES
Factors that influence the development and persistence of the specific and non-specific
immune responses after BCG vaccination include the following:
n BCG substrains; in in vitro cultures of bacteria, new strains or varieties of the original
bacteria may arise due to slight changes in the mediator growth conditions. These new
colonies of bacteria may have slightly different physiological and biochemical proper-
ties which may render them pathological to the host.
n The inoculating dose of the living bacteria may also be critical, because an excessive
amount of bacterial toxins may introduced.
n To introduce the bacterial antigen into the host, a mixture of dead and living organ-
isms is inoculated at the site of vaccination. If the inoculum contains a larger propor-
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