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Making vaccines against African swine fever virus

December 25, 2019


African swine fever is a very serious infectious
that affects domestic pigs and wild pigs. It was first found in East Africa. It was
present in a wild life reservoir of warthogs and soft ticks that live in warthog borrows.
In the early 1900’s it spread to domestic pigs that came into contact with the wild
life and in the domestic pigs it causes an acute haemorrhagic fever with very high death rates.
Since that time the disease spread through sub-Saharan Africa and to Europe twice 1957
and 1960. It was eventually eradicated from Europe in the mid 1990’s except for Sardinia.
Since 2007 the disease was introduced into Georgia in the Caucuses region and from there
it spread to the Russian Federation and into Eastern Europe.
Most isolates of the virus cause acute haemorrhagic fever, so the clinical signs are at first
quite non-specific. So there is high fever, loss of appetite, lethargy, at later stages
some signs of haemorrhage might be observed for example around the tips of the ears or
around the stomach and you might observe diarrhoea including some bloody diarrhoea and eventually
death occurs within 10-15 days usually. The disease spreads mainly by direct contact between
infected animals and also by contact with infectious materials. Infected pigs have very
high levels of virus in blood and in secretions including urine, faeces and oral nasal secretions.
Pigs in direct contact become infected quite readily, the virus is very stable in the environment
and in infected meat, so indirect contact either with ingestion of pork or by movement
of infected vehicles or other materials can also be a route for infecting pigs.
Measures for control rely on rapid diagnosis and then the implementation of quarantine
and movement restrictions. So there is no vaccine, not the possibility of using vaccination
to control disease spread. The pigs that we use mostly come from high animal health status
farm. Most of the experiments we carry out are vaccination experiments, where we want
to compare different types of vaccines. Generally our experiments would each have 18 pigs in
3 groups for example and we introduce our control group of non-immune pigs before challenge
with the virulent virus so we probably have around 21 pigs per experiment and we may do
4/5 experiments per year, so we are using between 80-100 pigs per year.
As much as possible we use preliminary tests in cell culture, for example one approach
we use to develop vaccines is to delete genes from the virus genome to try and produce a
virus that is attenuated, that is it doesn’t cause disease but can induce an effective
immune response that protects pigs against challenge. Currently there is not really any
effective method to test a vaccine in-vitro so we have to us animals to test the safety
and efficacy of vaccines. The classic approaches that were used to produce
the vaccines that have been effective against other viruses haven’t worked for African
swine fever. We currently have two approaches to produce vaccines. One is to try and improve
the safety of live attenuated vaccines and by manipulating the genome in different ways
and trying to understand more about the immune response and what leads to protection and
what leads to chronic disease for example. Another approach is to try and identify which
of the many proteins that are coded for by African swine fever virus can induce protection.
We first we have to identify which of the 165 proteins might induce protection. To do
this we have used immune cells from protective pigs and screened those against a library
of short peptides sequences, containing sequences from the virus to identify which are recognised
by the immune lymphocytes. We have taken the genes for those proteins and cloned them into
safe virus vectors that don’t replicate in the pig. These are vectors that are widely
used for vaccine production and are known to have a safe profile. We are currently carrying
out experiments where we immunise pigs with pools of these virus vectors each expressing
different African swine fever proteins and then measure the immune responses and trying
to determine which might induce a protection against challenge. Ultimately, we have to
test vaccines in animals because there is no effective correlation between what happens
in- vitro and what you observe in animals.

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