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1. Dressed to Kill
What do infectious disease agents
have in their wardrobes?
A presentation by Professor Sunetra Gupta
Professor of Theoretical Epidemiology at the Department of Zoology, University of Oxford
Bug drawings by Isolde Hill
2. Infectious diseases continue to be a
huge problem for us, despite the huge
progress made in the 20th century in
developing antimicrobial drugs and
vaccines.
Every year, at least 2 million people die
from diseases that are preventable by
vaccines, mainly in developing countries
that do not have the infrastructure to
deliver them effectively.
3. A good many more die from infectious
diseases for which we have no vaccines:
malaria, for instance, claims the lives of
around 800 000 young children every
year.
We also have no vaccines against some
the major killers of adults like HIV/AIDS.
4. Why do we have vaccines against
some diseases but not against
others?
To understand this, it’s useful to
conceptualise an infectious agent as
being in possession of their very own
wardrobe, from which they are
obliged to select an outfit in order to
be competent at infecting and
surviving within us.
8. So when an infectious disease
agent manages to breach our
first-line defences and get into us,
it grows in number and can make
us ill - even kill us - but more
typically we recover and go on to
become immune.
9.
10. The trick with vaccination is to
make us immune without
allowing us to get sick.
14. …this works for cholera and
whooping cough (that is to say,
the bugs that cause them).
15.
16. Another way of doing it is to keep
the bugs alive but weaken them
so that they can’t make you sick
anymore (and certainly can’t
transmit to another person).
17.
18. This how we’ve made vaccines
against diseases like measles,
mumps and polio.
19.
20. It is even possible to strip the
little beasts and just inject us with
the garments alone.
Such sub-unit vaccines are used
against Hepatitis B and HPV.
21.
22. Which brings us to what these
garments really represent – they
are in fact the bits of the
pathogen that our immune
systems recognize.
23.
24. These may be:
•
fragments of the loops that stick out of the
virus which help it attach and get into our
cells, or
•
some kind of channel in a bacterial
membrane that it uses to transport
nutrients, or
•
in the case of malaria – which hides in red
blood cells – proteins that the bug sticks on
the surface of the red blood cell to help it
stick to our blood vessel lining.
26. In all cases, they are essential to the
machinery of the bug – otherwise it
could of course just jettison the
costume.
27. So what this means is that when a person
becomes immune to an infectious disease
agent dressed all in green, they can be
infected by the same bug as long as it
returns in a completely different outfit.
29. This opens up the option for the bug to change
its clothes and come back – and this is a
strategy exploited, for instance, by influenza.
It is envisaged that once there has been an
epidemic – let’s say of this entirely green strain
– then the virus mutates in a fairly leisurely
manner to a new form which then causes a
new epidemic.
30. The current vaccine we have for influenza
appears to require updating every few years as
the virus adopts ever-new disguises to infiltrate
its host population over and over again.
This business of changing clothes is also
something the HIV virus does inside of an
infected person, and the malaria parasite is
injected into a person carrying a whole suitcase
of disguises.
32. Not all pathogens have this privilege
– measles, for instance, has a very
limited wardrobe – this is why we’ve
been so successful at making a
vaccine against measles.
33.
34. And it’s why we haven’t got a vaccine
yet against malaria or HIV – and why
the influenza vaccine needs updating
every few years when it returns in a
new outfit.
35.
36. But does influenza really have an
unlimited wardrobe?
The dogma is that the influenza virus
has an almost unlimited wardrobe
which it slowly samples until it
comes up with the appropriate
outfit.
40. …and also that it may have quite a
limited wardrobe (because, as I’ve
mentioned, the clothes actually
represent essential parts of the
virus that it cannot afford to vary
too much).
41.
42. We set out to explore this using a
mathematical model whose innards I
will briefly show just as an antidote
to these cartoons.
43. THE MACHINERY
zax
part of the population immune to strain ax
dzax
= lax (1- zax ) - m zax
dt
part of the population immune to any strain j related to ax
dwax
= å l j (1- wax ) - m wax
dt
j
part of the population infectious for strain i
dyax
= lax ((1- wax ) + (1- g ) ( wax - zax )) - s yax
dt
44. What the model revealed was an
alternative mechanism for the antigenic
evolution of influenza:
After an epidemic, the virus is at liberty
to select various combinations of the
available garments but most of these do
not work because the immune
responses - present in people who have
previously been infected - will recognise
either the hat or the shoes or the skirt.
45. HAS ORDERS TO DESTROY ANYTHING WEARING EITHER:
A GREEN HAT
or
A GREEN TOP
or
A GREEN SKIRT
or
GREEN SHOES
46. Our theory explains why influenza does
not explode in its variety of outfits each
time it is called upon to find a new one
that would escape immune surveillance.
If the virus only has a small selection of
hats, coats, gloves - it will have to try all
the different combinations until it comes
up with something that works.
47.
48. So we are currently exploring the
possibility - using a combination of
mathematical modelling and
experimental work - that the
wardrobe of influenza is in fact not as
diverse as is currently believed.
49.
50. We believe this will open up
possibilities for control – if we can
target the less diverse parts of
influenza’s wardrobe, we can make
sure that the virus is…
