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less active or even inaccessible for antibody binding. Finally, important
protein properties such as solubility and stability, which are difficult
to predict, may make the artificial antigen unsuitable for diagnostics.
Thus, limited QSAR knowledge does not completely preclude the
engineering of artificial proteins with some useful diagnostic proper-
ties, but nevertheless does not allow for the reliable rational design of
superior diagnostic targets.
An alternative strategy based on the use of carrier proteins is
applied mainly to engineering of vaccines. A carrier protein is usually
selected based on its immunogenicity or capacity to induce a strong
immunoresponse. If a carrier protein is highly immunogenic, the
design of an artificial protein capable of eliciting an immunoresponse
to some desired antigenic epitopes involves only inserting those epi-
topes into the carrier protein so that the inserts do not adversely affect
the immunogenicity of the carrier and would be recognized by immuno-
competent cells responsible for producing the antibody response.
Although many proteins can be used as carrier proteins, the nucleo-
capsid, capsid, and envelope proteins of viruses are the most useful.
These proteins expressed in heterologous systems usually maintain
their propensity to assemble into complex aggregates with regular
structures reminiscent of virions. The recombinant protein structures
are frequently referred to as virus-like particles (VLPs). Many researchers
consider VLPs , which seem to be assembled into “natural” confor-
mations, as the most suitable protein structures for efficient antigen
presentation and/or clonal selection during the development of an
immunoresponse to viruses. 45 Because of their strong antigenic and
immunogenic reactivity and their use as targets for protein engineer-
ing, VLPs have been extensively explored as diagnostic reagents and
vaccines. 71-73
Although many laboratories have devoted significant effort to the
development of the VLP strategy and have obtained encouraging
results, the approach remains primarily in the domain of research and
has yet to be applied to actual vaccine development. The major prob-
lem is that the strategy imitates active protein structures that have
several important functions (e.g. packaging and protection of viral
genetic material, cell receptor binding, cell penetration, and regulatory
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