Biomedical Engineering Reference
In-Depth Information
Figure 13.12
Strategy adopted for the development of an engineered vaccine vector. Refer to text for
additional detail
Adenoviruses also display potential as vaccine vectors. These double-stranded DNA viruses
display a genome consisting of in the region of 36 000 bp, encoding approximately 50 viral genes.
Several antigenically distinct human adenovirus serotypes have been characterized, and these
viral species are endemic throughout the world. They can prompt respiratory tract infections and,
to a lesser extent, gastrointestinal and genitourinary tract infections.
Live adenovirus strains that cause asymptomatic infection and which have proven to be very safe
and effective adenovirus vaccines have been isolated. Unlike vaccinia, few sites exist in the adenoviral
genome into which foreign DNA can be integrated without comprising viral function. Furthermore,
packing limitations curb the quantity of foreign DNA that can be accommodated in the viral genome.
However, an approximately 3000 bp region can be removed from a section of the genome termed the
E3 region. This facilitates incorporation of pathogen-derived or other DNA at this point.
Recombinant adenoviruses containing the hepatitis B surface antigen gene, the HIV P160 gene,
the respiratory syncytial virus F gene, and the herpes simplex virus glycoprotein B gene have all
been generated using this approach. Many have been tested in animal models and have been found
to elicit humoral and cell-mediated immunity against the pathogen of interest.
The use of recombinant viral vectors as vaccination tools displays considerable clinical prom-
ise. One potential complicating factor, however, centres around the possibility that previous re-
cipient exposure to the virus being used as a vector would negate the therapeutic effi cacy of the
product. Such prior exposure would likely indicate the presence of circulating immune memory
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