Adjuvant technology

• An adjuvant is defi ned as any material that enhances

the cellular and/or humoral immune response to an
antigen.

• Adjuvants thus generally elicit an earlier, more

potent and longer-lasting, immunological reaction
against co-administered antigen.
• In addition, the use of adjuvants can often
facilitate administration of reduced quantities
of antigen to achieve an adequate
immunological response.
• An ideal adjuvant should display several specific
characteristics.
These include:

• safety (no unacceptable local/systemic responses);

• elicit protective immunity, even against weak

immunogens;
• be non-pyrogenic;
• be chemically defi ned (facilitates consistent
manufacture and QC testing);
• be effective in infants/young children;
• yield stable formulation with antigen;
• be biodegradable;
• be non-immunogenic itself
Overview of the adjuvant preparations
 Adjuvant mode of action

• Adjuvants are a heterogeneous family of

substances, both in terms of their
chemical structure and their mode of
action.
The observed adjuvanticity of any such substance may
be due to one or more of the following factors:

• Depot formation of antigen: This results in the

subsequent slow release of the antigen from the site
of injection, which, in turn, ensures its prolonged
exposure to the immune system.

• Enhanced antigen presentation to the cells of the

immune system.

• The direct induction of immuno-stimulatory

substances, most notably interleukins and other
cytokines.
 Mineral-based adjuvants

• Most commonly employed are aluminium

hydroxide and aluminium phosphate.
• The principal method by which aluminium
adjuvanted vaccines are prepared entails
mixing the antigen in solution with a
preformed aluminium phosphate (or
hydroxide) precipitate under chemically defi
ned conditions (e.g. of pH).
 • Adsorption of the antigen to the
aluminium-based gel ensues, with such
preparations being generally termed
‘aluminium-adsorbed vaccines.
• The major mode of action of such products appears
to be depot formation at the site of injection.

• The antigen is only slowly released from the gel,

ensuring its sustained exposure to immune
surveillance.

• The aluminium compounds are also capable of

activating complement. This can lead to a local infl
ammatory response, with consequent ttraction of
immunocompetent cells to the site of action.
 Oil-based emulsion adjuvants
• Freund’s complete adjuvant (FCA):

• This product essentially contained a mixture of

paraffi n (i.e. mineral) oil with dead
mycobacteria, formulated to form a water-in-
oil emulsion. Arlacel A (mannide mono-oleate)
is usually added as an emulsifier.
• Freund’s incomplete adjuvant (FIA) is a similar
product. It differs from FCA in that it lacks the
mycobacterial component and, consequently,
displays somewhat lesser adjuvanticity.
• The mode of action of FIA is largely attributed
to depot formation.

• The mycobacterial components in FCA have

additional direct immunostimulatory
activities.
Bacteria/bacterial products as adjuvants

• Selected microorganisms have been identifi ed

that can trigger particularly potent
immunological responses (immunostimulatory
properties).

• Examples include various mycobacteria,

Corynebacterium parvum, Corynebacterium
granulosum and B. pertussis
• Fractionation of mycobacteria resulted in the identifi cation
of two cellular immunostimulatory components, namely
TDM and MDPs.

• Both are normally found in association with the

mycobacterial cell wall.

• TDM is composed of a molecule of trehalose linked to two

molecules of mycolic acid (a long-chain aliphatic
hydrocarbon-based acid) found almost exclusively in
association with mycobacteria.

• TDM, although retaining its adjuvanticity, is relatively non-

toxic.
 • The structure of the native
immunostimulatory MDPs was found to be N-
acetyl muramyl-Lalanyl- D-isoglutamine.

• Native TDM is a potent pyrogen and is too

toxic for general use as an adjuvant.