Jan
21
ADDomer – A new kind of vaccine for untreatable infection


In our latest study we combine
synthetic biology and cloud computing, two incredibly powerful techniques, to create
a new chikungunya vaccine candidate. Our approach is not confined to chikungunya
alone, but can cover the entire universe of infectious diseases where antigenic
epitopes exist. A half a century ago, many people had
started to think that infectious diseases had been solved – and we were
totally wrong. Infectious diseases have never been more of a problem than they
are today. Our best defense and most successful defense against infectious
diseases is vaccination. Chikungunya is one of a group of viral infections that’s spread around by mosquitoes. It is usually confined to sub-Saharan Africa
but because of deforestation and climate change has started to spread all over
the world also reaching Europe and the US and all developed countries. And it’s
just one of the whole bunch of these infections, against which we have no
treatments and no vaccines at present. A major problem with vaccines at the
moment is that they need to be refrigerated for storage and for
transport, otherwise they become inactivated. We have developed a new
class of synthetic vaccine. We call it the ADDomer. It consists of a
protein, which we have engineered so that it forms a large particle structure
resembling a virus. This technology is unique because
it doesn’t rely on a cold chain. We can mass-produce it at low cost, which is basically ticking all the boxes
in what a very good vaccine should be. This is the ADDomer. We have applied synthetic
biology to engineer the surface of the ADDomer. By putting small and harmless
bits and pieces of the chikungunya virus on top of the surface of the ADDomer, we
create a particle which looks like chikungunya but is not. But when the
immune system sees it, it develops antibodies against it, which will be
protecting also when the real virus arrives. In order to be able to do so,
we had to know the structure of the ADDomer at near-atomic resolution.
This we determined by cryo-electron microscopy and we applied, for the first
time, cloud computing to compute the structure from the data which we got out
of the microscope. We got a very strong immune response in our studies,
which showed us that we are on the right way. I think this is an example of really
a step-change, where up until now we’ve had to kind of accept the materials that
biology gives us. This represents a more deliberate attempt to actually engineer
the bits and pieces that you need to make a vaccine work. This was a highly
interdisciplinary study involving many scientists with complementary expertise. In Bristol we have a unique ecosystem for this kind of work, which is hard to find
elsewhere. The IT team here in Bristol, together
with their colleagues at Oracle, did an excellent job to connect the data which
comes out of the cryo electron microscope with the cloud infrastructure. Cloud computing fundamentally is the ability to be able to get computing or storage
or networking access as a utility. This was a very interesting project. The
amount of data that was required to be processed and the complexity of the
computational models required a fairly novel approach to be able to use
different kinds of hardware and cloud infrastructure for different parts of a
complex workflow. What the team here have done is demonstrated an extremely
cost-effective and fast way to analyze cryo EM data and even better the research
team at Bristol have published their work into open source, so it makes it
very easy for other groups working with cryo EM to be able to leverage that. What cloud computing does is allow us to dynamically create resources to fit the
exact problems that we’re trying to solve. The tool we created is called
‘cluster in the cloud’ because it allows anyone to create their own personal
high-performance computing cluster in the cloud. What we need to do now for the
next step, is to continue the validation in other infectious disease areas and to
continue to develop our technology. Our ambition is to make vaccine candidates
based on our technology against a whole range of human and also veterinary
diseases. In our current paper, we already show more than a dozen other vaccine
candidates which we have made. We have now more than 30 altogether and we are very interested to see how powerful our technology really is.