An Emerging Solution—Virus-Like Particles (VLPs)
There are a number of expression technologies currently in use for the production of VLPs, including mammalian, insect and
microbial-based systems. A microbial-based platform approach is ideally suited for this application. They are simple, cheap,
and have a rapid turnaround time required for pandemic vaccine production. A microbial production system may also be favourable
because, unlike insect and mammalian systems, they do not require incorporation of specific viral inactivation or reduction
steps into the production process, which may be problematic when processing such large molecules as VLPs.
Figure 2. Scanning electron microscope image of a preparation of virus-like tandem core particles displaying (a) Hepatitis
A virus complete P1 polypeptide or (b) Hepatitis B virus surface antigen from E. coli (picture courtesy of iQur Ltd.)4
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VLPs for pharmaceutical applications typically exploit the inherent ability of many viral structural proteins to self assemble.
For instance, VLPs are formed when the 16 kDa hepatitis B viral core proteins spontaneously self-assemble to form icosahedral
VLP structures of approximately 30–50 nm in a host cell as shown in Figure 2. They can be engineered to display a range of
surface antigens, such as the hemagglutinin (HA) surface antigen providing a useful carrier for vaccine platforms. By presenting
antigens in a VLP form, where typically 240 copies of the same protein can be presented in a single particle, it may be possible
to stimulate the immune system in a more appropriate way than can be achieved through presentation of dissociated antigens
adjuvanted with other macromolecules. One such example is iQur Ltd's (London, UK) tandem core VLP expression technology.4
Manufacturing Strategies
Vaccines are complex and diverse biomolecules ranging from recombinant subunit antigens to live attenuated organisms. Therefore,
a range of production technologies and process formats are required to manufacture sufficient quantities of these varied products.
However, this wide range of production methods can be problematic because each one requires specific capital expenditure and
specialized development approaches coupled with operator expertise and concomitant high cost, which limits the availability
of vaccines to developing nations. With current comparisons suggesting productivity in the range of 10-g/L for prokaryotic
systems versus a realistic short- or medium-term 3-g/L goal from eukaryotic processes, there is a growing trend and focus
toward a lower number of production platforms by manufacturing in similar expression systems including microbial backgrounds.
These microbial platforms in particular offer an attractive solution to the often numerous challenges associated with the
development of vaccine products. The rapid establishment of strains expressing the target recombinants is especially attractive
to product developers, often facilitating early efficacy studies from multiple product variants for pandemic threats while
paralleling process development and manufacturing activities.
In addition to a reduction in process costs of goods and the process durations associated with microbial systems, the production
scales required for low-dose, high-potency products have an associated reduction in capital expenditure for manufacturing
facilities; thus an all round attractive proposition for reactive development of vaccine products.
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