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CATEGORY: VACCINES & THERAPEUTICS
ADJUVANTS: PARTICULATE ANTIGEN DELIVERY SYSTEMS
Adjuvants: particulate
antigen delivery systems
Rebecca Helson, London, UK
Liposomes are phospholipid vesicles often used in combination with MPL to facilitate Th1
responses. It is therefore difficult to determine the precise contribution of liposome to the response.
The majority of formulations in development are based on naturally occurring phosphatidylcholine.
Virosomes are very similar to
liposomes but are based on viral
membrane proteins to contribute to
immunostimulation. Inclusion of viral
membrane
proteins
such
as
haemagglutinin (Figure 1) exploits the
targeting and fusogenic properties of
this protein, perhaps improving the
delivery of the antigen into the cell
cytosol.
Antigen
Neuraminidase
Phospholipid
Haemagglutinin
Figure 1. Diagrammatic representation of the virosome structure.
Adapted from http://www.futura-sciences.com/fr/doc/t/medecine1/d/grippe-aviaire-et-prevention-chez-lhomme-33_682/c3/221/p3/
Immunostimulatory complexes (ISCOMs) comprise
of
immunostimulatory
fractions
of
saponin
incorporated into lipid particles also containing
cholesterol, phospholipids and cell membrane
antigen. ISCOMs are generally capable of inducing
both
antibody
and
T-cell
responses.
Non-ionic surfactant vesicles (NISV) have similar
properties to liposomes and are manufactured in a
similar way using amphipathic molecules induced to
form vesicles. They consist of 1-mono palmitoyl
glycerol, cholesterol and dicetyl phosphate. NISVs are
more stable in air than liposomes and do not require
special
handling
or
storage.
Chitosan is a biodegradeable polysaccharide
produced by the hydrolysis of chitin, a naturally
occurring polysaccharide found in the shellfish shell.
Chitosan contains positively charged sites throughout
the structure which facilitate transport across the
mucosal epithelium; it therefore has potential for use
as a mucosal vaccine adjuvant.
Polylactide co-glycolide (PLG) has a
good safety profile in humans as they
have been used for sutures and
controlled drug delivery therapeutics
for many years. PLG microparticles are
created using a modified solvent
evaporation process that creates
cationic microparticles (Figure 2) to
which the DNA can be adsorbed and
thus enables a broad approach for a
range of other DNA vaccines. This
polymer has been shown to be
targeted by antigen presenting cells,
in particular dendritic cells.
Figure 2. Scanning electronic
micrograph of PLG
microspheres (Lima and
Rodgrigues. Brazilian Journal
of Medical and Biological
Research 1999;32:171-180)
5 µm
© The copyright for this work resides with the author
MF59 is an oil-in-water emulsion appearing as small, uniform oil droplets and has shown great
promise as a vaccine against influenza for the elderly. Safety and immunogenicity studies in an
elderly population showed the MF59-adjuvanted influenza vaccine to be well tolerated with a
satisfactory safety profile. The resulting vaccine, FLUAD® was first licensed in Italy in 1997.
Success with the influenza sub unit vaccine has encouraged further work with other viruses
including the HIV envelope protein. Clinical results from clinical trials are encouraging suggesting
MF59 to be safe and well-tolerated in humans.