Biomedical Engineering Reference
In-Depth Information
13.4.6 Diffi culties associated with vaccine development
A number of attributes of HIV and its mode of infection conspire to render development of an
effective vaccine less than straightforward. These factors include:
•
HIV displays extensive genetic variation even within a single individual. Such genetic variation
is particularly prominent in the viral
env
gene whose product, gp 160, is subsequently proteo-
lytically processed to yield gp 120 and gp 41.
•
HIV infects and destroys T-helper lymphocytes, i.e. it directly attacks an essential component
of the immune system itself.
•
Although infected individuals display a wide range of antiviral immunological responses, these
ultimately fail to destroy the virus. A greater understanding of what elements of immunity are
most effective in combating HIV infection is required.
•
After initial virulence subsides, large numbers of cells harbour unexpressed proviral DNA. The
immune system has no way of identifying such cells. An effective vaccine must thus induce the
immune system to (a) bring the viral infection under control before cellular infection occurs or (b)
destroy cells once they begin to produce viral particles and destroy the viral particles released.
•
The infection may often be spread not via transmission of free viral particles, but via direct
transmission of infected cells harbouring the proviral DNA.
13.4.7 AIDS vaccines in clinical trials
A number of approaches are being assessed with regard to developing an effective AIDS vaccine.
No safe attenuated form of the virus has been recognized to date, nor is one likely to be developed
in the foreseeable future. The high level of mutation associated with HIV would, in any case,
heighten fears that spontaneous reversion of any such product to virulence would be possible.
The potential of inactivated viral particles as effective vaccines has gained some attention, but again
fears of accidental transmission of disease if inactivation methods are not consistently 100 per cent
effective have dampened enthusiasm for such an approach. In addition, the stringent containment con-
ditions required to produce large quantities of the virus render such production processes expensive.
Not withstanding the possible value of such inactivated viral vaccines, the bulk of products
assessed to date are subunit vaccines. Live vector vaccines expressing HIV genes have also been
developed and are now coming to the fore (Table 13.12).
Much of the preclinical data generated with regard to these vaccines entailed the use of one of
two animal model systems: simian immunodefi ciency virus infection of macaque monkeys and HIV
infection of chimpanzees. Most of the positive results observed in such systems have been in asso-
ciation with the chimp-HIV model. However, no such system can replace actual testing in humans.
Most of the recombinant subunit vaccines tested in the fi rst half of this decade employed gp 120
or gp 160 expressed in yeast, insect or mammalian (mainly CHO) cell lines. Eukaryotic systems fa-
cilitate glycosylation of the protein products. Like all subunit vaccines, these stimulate a humoral-
based immune response but fail to elicit a strong T-cell response. The failure to elicit a cell-based
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