Biology Reference
In-Depth Information
short antigenic regions, is used mainly to develop reagents with
improved diagnostically relevant properties. Because antibody bind-
ing is a relatively simple protein-protein interaction process and/or
because antigenic epitopes are usually discovered by binding with
antibodies directly (the most essential property for diagnostic targets),
the MEP approach can be used to obtain artificial antigens suitable
for diagnostics.
60-64
The structural design of vaccines is more difficult
because antibody eliciting is a significantly more complex biological
process and the pathogen neutralization mechanisms are not fully
understood. In this case, antigenic epitopes of interest are frequently
inserted into carrier proteins that serve to stimulate an immunore-
sponse against the inserted epitopes.
The MEP strategy involves the use of broadly and strongly
immunoreactive antigenic epitopes to design and construct synthetic
genes that encode artificial polypeptides composed of these epitopes.
MEPs imitate only the diagnostically relevant immunologic properties
of natural antigens without regard for other associated functions.
Because MEPs are composed of epitopes that are relevant only to
diagnostics, they are expected to significantly reduce the opportunity
for nonspecific reactivity
65-70
since ~3%-4% of pathogen-specific anti-
bodies may cross-immunoreact with host-specific antigens.
69
The
MEP strategy is flexible and allows researchers to combine in one
polypeptide several copies of antigenic epitopes from many different
antigens and sequence variants of these antigens.
61-64
Despite its advantages, the MEP strategy has not become a main-
stream method for obtaining diagnostic reagents. Since the strategy
relies on the use of antigenic epitopes modeled with synthetic pep-
tides, it does not involve conformational epitopes, which comprise a
significant pool of diagnostically relevant epitopes. In addition, com-
bining antigenic regions in one protein generates many junctions
between these regions, which could potentially generate new epitopes
and interfere with accurate antibody detection. Although antigenic
epitopes are reproduced when inserted into artificial antigen, there is
no assurance that these epitopes are fully functional. Artificial combi-
nation of several epitopes also raises concerns about adverse interfer-
ence between these epitopes, which may render some epitopes to be
