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thermostable viral vaccines
Developing a heat stable oral polio vaccine (OPV)
had been for many years an unrealisable goal for
the World Health Organization. The three Sabin
poliovirus strains incorporated in OPV will lose most
of their potency within a few days at ambient
temperatures. A solution containing 10 billion infective
virus particles per cubic centimetre
1010
particles/cm3
would see this activity fall to around
106
infectious particles/cm3 in one week at
37oC. This represents a loss of 4 factors of 10 or 4
logs.
The WHO defined a goal of less than 0.5 logs loss of
activity after 1 week at 37oC.
Karl Simpson, who had previously headed the
European Molecular Biology Laboratory's deuteration
facility, recognised that the increased stability of
deuterium bonds as opposed to hydrogen bonds
(of the order of 0.25 kilocalories/Mole) might offer
hope of stabilising water bridges in the virus
particles, leading to an overall strengthening of the
viral particle against ambient thermal denaturation
- as well as increased resistance to ambient enzyme
activity.
By simply suspending viruses in a 90% solution of
buffered heavy water the WHO goal for stability
was achieved! This simple solution to a long-term
problem demonstrates that lateral or "out of the
box" thinking can allow major work to be executed
without access to expensive facilities. A little
creativity, access to relevant literature and simple
confirmatory tests in independent laboratories
were able to establish a significant advance in
medical science.
This technology is patented and has been licensed
to major players in the vaccine sector.
Other applications beg to be developed.
the "Pseudo-Live" rational attenuation concept
This revolutionary technology applies the
principles of "rational attenuation" to the development of
a safe vaccine that stimulates the body's immune
system to combat HIV infection. Bénézech
-
Simpson call this the "Pseudo-Live"
vaccine concept.
According to Dr Jay Levy, MD, Professor of
Medicine at the University of California,
San Francisco:
"We have to design a vaccine that will
mimic the three dimensional structure of the
virus and will act like the pathogen, having
some low level of replication, yet not
causing illness." (Genetic Engineering News,
1995)
We have adopted an approach which will achieve
exactly that.
We summarise the major steps below:
1 key genes, including that coding for reverse transcriptase (RT) are cut out of the HIV virus genome.
2 the virus cannot infect or
replicate without RT.
3 so it is useless as a
vaccine - but:
4 RT genes are
introduced not into the virus, but into cells in which the virus can
replicate.
5 in these cells the
handicapped viruses can multiply.
6 the gene make RT protein.
7 RT
allows the virus to replicate its nucleic acid - which is missing the gene.
8 we wonít worry about other genes here.
9 the replicating viruses
wrap up some of the RT protein.
10 if these gene deficient
viruses enter a human - as a vaccine.
11 the presence of RT
protein allows the virus to replicate until the protein is
broken down by
normal body chemistry. This usually takes place quite
quickly.
12 so the viruses multiply a limited
number of times and then come to a full stop.
13 unlucky for some - the HIV viruses in
this case. The infection stops here.
14 the multiplication has been just
enough to stimulate the immune system, without causing
disease.
15 the person infected with pseudo-live
virus is now protected from real HIV infection.
Details on this project can be obtained
directly from Bénézech - Simpson.
We have established a management team and a
business plan which is capable
of supporting this concept as a stand-alone
company focusing on HIV and other
retroviruses. We can also adapt this technology to
gene therapy. Given the high
containment facilities implied in the development
of this vaccine we will need to
generate support of the order of €10 million
to take the project through to animal
trials and demonstration of
principle.
We are delighted to develop our ideas in partnership with those
having
an established presence in the markets of relevance. Our contact
details
are on our home page.