Biology Reference
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interactions with host proteins) among which immunological activi-
ties are of somewhat peripheral importance. Since the determinants of
high immunogenicity in these protein structures are unknown,
researchers are forced to imitate the structures in their entirety in the
hope that the desired immunological properties will be reproduced.
However, even though immunological properties are modeled with
these structures, many other properties are almost certainly repro-
duced as well. In addition, VLPs are complex protein structures that
contain many antigenic epitopes, only a fraction of which contribute
to the intended use in virus neutralization. All of these factors limit
the value of this strategy for vaccine engineering.
Although all currently available vaccines are affected by similar
constraints, rational vaccine design implies improvement, rather than
reproduction, of protein properties by facilitating the desired
immunoresponse and excluding or at least reducing any potential
shortcomings. Rationally designed proteins should perform to speci-
fications and should not include functions unrelated to their primary
purpose. The design of artificial antigens or immunogens should
therefore be limited to relevant immunological properties without
regard to other properties associated with the naturally occurring
antigens. Such design can be achieved using building blocks with
known simple elementary functions. However, since QSAR for virus
neutralization is not sufficiently understood, such elementary build-
ing blocks are not available. Therefore, vaccines cannot yet be con-
structed using this design. This lack of knowledge limits engineering
choices to the use of rather complex structures such as VLPs to stim-
ulate desired immunoresponse at the price of including many proper-
ties unrelated to pathogen neutralization.
Researchers can overcome the limitations of the carrier protein
strategy to some extent by using a carrier derived from the same virus
for which the vaccine is engineered. For example, use of the HBV
nucleocapsid protein (C), which is efficiently assembled into VLP in
many expression systems,
74-82
as a carrier protein for the neutralizing
epitopes derived from HBV surface antigen (HBsAg) allows the neu-
tralizing properties of both proteins to be combined.
77,79,83-86
To
reduce irrelevant immunological activity, VLPs that elicit a protective
