Page 802 - Veterinary Immunology, 10th Edition

FIG. 24.12 Nanoparticles come in different sizes, and this greatly
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influences the nature of immune responses to vaccines.

It is important to note, however, that particle size is critical. Thus
conventional aluminum adjuvants employ microparticles (2-8 µm
in size) and promote Th2 responses. If, however, they are reduced

to nanoparticle size (200-1500 nm), they favor Th1 responses.
Nanoparticle adjuvants show considerable promise in new
generation vaccines. They can be made from many different
compounds such as poly amino acids, polysaccharides, polystyrene,

and biodegradable polymers, as well as nondegradable elements
such as gold, silver, iron, and silica. They can be engineered to
display a mixture of antigens and co-stimulating molecules on their
surface so that the immune response is optimized.

Nanoparticles have unique immunological properties that can be
manipulated by altering their size, shape, charge, and
hydrophobicity. They can be coated with unique combinations of
antigens, cytokines, adhesion molecules, immunomodulators, and

co-stimulatory ligands, and in effect may be specifically tailored to
generate key protective processes. By associating antigens with
pattern recognition receptors such as the NLRs, and TLRs,
nanoparticles can trigger cytotoxic lymphocyte responses to

antigens that normally won't do this. Intradermal and
intramuscular administration can induce strong immune responses
while intravenous administration may induce tolerance.
Virus-like particles (VLPs) are nanoparticles 20 to 100 nm in size.

They may be constructed using viral protein subunits to form, in
effect, a viral capsid. Alternatively, they can be entirely synthetic,
made by chemical synthesis of carefully designed subunits. VLPs,
although they may resemble viruses, do not contain genetic

material and cannot replicate and are thus very much safer than
conventional virus vaccines. Other molecules can be incorporated
into them such as TLR ligands or other cell-targeting molecules.
VLPs and other nanoparticles are sufficiently small enough that
they can penetrate tissue barriers, travel to draining lymph nodes,

and are readily taken up by antigen-presenting cells. Especially
when coupled to specific cell-targeting molecules, nanoparticles are
much more effective than microparticles at being taken up by cells

of the immune system. They promote DC activation and

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