Biology Reference
In-Depth Information
of antigens derived from
in vitro
sources include influenza A vaccine
derived from
in vitro-
infected embryonated chicken eggs
14,15
and hepa-
titis A virus (HAV) vaccine and diagnostic reagents obtained from
in
vitro-
infected cell cultures.
16-18
However, despite the number of vac-
cines and diagnostic materials developed from
in vivo
or
in vitro
sources
and their use in the prevention and diagnosis of many common viral
infections, serious concerns exist about the safety and cost-effectiveness
of viral materials derived from tissues infected with live virus.
19-26
Mistakes in the handling of infectious material prepared for vaccine pro-
duction can have disastrous consequences. The distribution of infec-
tious virus with some batches of the original Sabin poliovirus vaccine in
the early days of a large-scale production of this vaccine is one of the
most infamous accidents in the recent history of live vaccines.
27
The application of recombinant DNA technology to medicine
promised an immediate and dramatic improvement in the safety of
inexpensive preparations of viral proteins. A notable example is the use
of HBV surface antigen obtained from transformed yeast to create an
efficient, safe, and affordable recombinant vaccine.
2,8,28-33
However,
the application of recombinant DNA technology to hepatitis B vaccine
development is unlikely to be duplicated for other viruses such as
human immunodeficiency virus (HIV) and hepatitis C virus (HCV),
which tenaciously defy attempts to develop an efficient preventive
vaccine. To a significant degree, the difficulties in developing HIV and
HCV vaccines are related to the limited knowledge of neutralizing
immunoresponses against different strains of these viruses.
34-40
As researchers realized that the straightforward approach to devel-
opment of a recombinant hepatitis B vaccine could not be applied
to other viruses and that new strategies were needed, they turned to
protein engineering, which was born in the early 1980s. Protein engi-
neering is the application of molecular techniques and scientific prin-
ciples to the design and construction of novel proteins with desired
properties. The spectacular developments over the last three decades
in the automatic high-throughput chemical synthesis of long pep-
tides
41-43
and deoxypolynucleotides
44
have built a solid technological
foundation for protein engineering. Although these advances in
molecular technology made the construction of very large proteins of
