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Calicivirus delivers vaccines in humans -

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Sarah Young: The virus infects rabbits, that's the natural host, and it causes a haemorrhagic
disease. So basically they bleed out of orifices and they die very quickly. But we are using it in
our own research in humans, and humans aren't a natural host of calicivirus so it doesn't cause a
productive infection in humans but we can use it as a vehicle to introduce different antigens for
infectious diseases and tumours into the human host.

Robyn Williams: I don't look like a rabbit but mammals are pretty much the same. I'm rather
surprised that you can tell me that a calicivirus, which you use as a sort of Trojan horse to get
another kind of vaccine into my body, won't affect me in any way. How do you know?

Sarah Young: We've tried it in cells. So it doesn't cause an active infection and cause killing or
lysis of cells in a culture. It doesn't do that with human cells, and that's the way we know. And
we also know obviously the farmers that released them in Otago in New Zealand here, none of them
got a productive infection or got any sign of disease and they were introducing huge virus titres
into the environment.

Robyn Williams: And of course what you need to do is get the vaccine to the right place in the
human body, and I've heard of some people who've used even a denatured AIDS virus.

Sarah Young: Yes, people are using attenuated viruses, so denatured or heat-killed viruses. So
they're viruses and they're used in routine...for example, the influenza vaccine. Denatured viruses
are used a lot in vaccines, so they can't infect a cell but they can provide all the proteins that
you might make an immune response to.

Robyn Williams: And they can get in.

Sarah Young: They can get into your body when you inject through a needle. However, it's your
phagocytic cells, certain cells that will pick it up and eat them, and that's how they get into the

Robyn Williams: What would happen if you just squirted the vaccine in without that carrier?

Sarah Young: We've tried this with the virus-like particle. We have a project looking at
transcutaneous vaccination and also vaccination across the mucosa, so up the nose for example, and
we know that we need some sort of adjuvant to help it get across that layer of skin or the mucous

Robyn Williams: And what sort of vaccines are you taking into people?

Sarah Young: The main thrust of our research a the moment is to use these virus-like particles as
carriers for tumour proteins, and we're trying to make tumour therapies and also vaccines against
tumours, so to prevent tumours. So we've got those in pre-clinical trials at the moment where we're
using them in vitro cultures, but the idea is that we'll use them eventually in humans. So we'll
initially make tailor-made vaccines. So I've got a collaboration with my old work in the UK, Cancer
Research UK, where a patient will come in, we'll [recept] out the tumour, we'll load those tumour
antigens onto the VLP and then we'll use that to reinject back into the patient to try and tickle
their immune system along and generate a strong immune response to that particular tumour that
they've got.

Robyn Williams: And by their extract of tumour they'll kill the tumour themselves in the end.

Sarah Young: Yes, that's exactly right. So we're trying to make the immune response seem like an
infectious disease, so normally you get quite tolerised to your own tumour, and tumours have ways
of dampening down the immune response. So you need something to really kick the immune response
into gear, and this is the way that we do that.

Robyn Williams: Is it working?

Sarah Young: We haven't tried in vivo yet, but it's certainly looking good in the animal models
that we've got of tumours. We've got it working very nicely in a melanoma model, and we are trying
it in some colorectal models as well, but we've just got another lot of research money to do
exactly that. So basically if you were to ask me this question in another two years time, I might
be able to answer it.

Robyn Williams: That's a date! Dr Sarah Young is a microbiologist at the University of Otago in New