Hello my name is Paul Moss, I'm Deputy Head of the College of Medical and
Dental Sciences in the University of Birmingham and in the next few
minutes i'd like to introduce some of the principles of vaccination against SARS-CoV-2.
this shows an outline of the virus structure and at the bottom in the cartoon you can see
the four major proteins in the virus nuclear capsid, spike, envelope and membrane and i want
to focus today on the spike protein which is the target for most current vaccine regimens
this is a structure of the spike protein it has two forms a globular form at rest and
then when activated a rod-like form you can see what a beautiful structure it is
and in this little video i can bring this alive by showing you how the virus binds to your cells
so here we will see the spike has two domains
the external red s1 domain and you can see here binding to your cells perhaps in the nose
and after that happens the spike is cleaved and this s2 domain unravels onto your cell
from the virus and then two of these spike proteins pull the virus envelope down
almost an anthropomorphic way to make sure that the virus can enter into your cells
this is a representation of from my colleague Gavin Screaton in Oxford of the top of the
spike domain it's called the receptor binding domain and you'll see in green the area of the
receptor binding domain that binds to the protein ace2 that allows entry into your cells and for
vaccination we need to induce antibodies that can block this interaction. What Gavin's been able to
do is to see where antibodies from people who are naturally infected with the virus
bind onto this green receptor binding domain and the valuable antibodies the ones in red they are
neutralising and they stop the virus being able to stick to your cells and that's what vaccination
must achieve. Here Gavin's actually looked at how the antibodies bind by cryoelectron microscopy you
can see this antibody sitting right on the top and stopping the rbd from binding to your cells
this antibody fascinatingly is stuck at 90 degrees but still very effective. So vaccination of course
this is Dr Jenner's house in Gloucestershire proud British history of vaccination and we're very
fortunate that we have three effective vaccines against SARS-CoV-2. How did these come about
well one of the major rules of biology is that you get dna the code from your mother and your dad
and then as you use it in cells you get a transcript formed called messenger rna
which is decoded into proteins the building blocks of your body
and most old vaccines in the past such as the one that Dr Jenner used were proteins
which are injected into your body to make an immune response but the first and important
vaccine candidate for SARS-CoV is mRNA so it's injecting the code for the spike protein
which your body then makes itself and induces an immune response so we have the different
classes of vaccine platforms at the current time mRNA vaccines and the adenovirus based vaccines
we will also see introduced soon protein vaccines and inactivated whole virus vaccines
this is the first report of the efficacy the clinical efficacy of the mRNA vaccine
and you'll see here two groups, in blue people who did not have the vaccine and this was the
number of infections they got over time you can see gradually increasing whereas in red
the people who received the vaccine you can see that new infections plateaued out very early
95% efficacy and you can look at very very early you can see protection happening at 11 days
after vaccination remarkably early and remarkably effective
and of course the joint committee on vaccination and immunisation has prioritised the different
groups which will get the vaccines and you can see that in the UK we're racing through
these groups very effectively because we know that age is the major determinant of mortality
but the virus can mutate. The mutation rate for this virus is low it's lower than influenza and
HIV and that gave us a lot of hope initially but we now know that this rate of change at one or two
per month can accumulate and lead to all these different subtypes of variants of virus
as you can see here and one of these variants this e484k variant can lead to loss of some of those
antibodies and loss of some immune recognition so we have a number of challenges we don't know
how long the immune response will last after vaccination, we don't know the response in immune
suppressed patients such as those with a cancer diagnosis we don't know if we can mix and match
the mRNA and adenovirus vaccines and that's being tested and we need to overcome these
variants either by generating very high levels of antibody or getting a specific vaccine against the
variants and of course our College of Medical and Dental Sciences is playing a strong position in this area
we're leading the national core studies program with Patrick Vallance and Chris Whitty
and we've invested a lot of money on studying vaccine immune correlates with my colleague
Professor Kearns leading on a study of patients with a cancer diagnosis
and my own team looking at immune senescence people over the age of 80 years
and seeing how effective they are at generating immune response to vaccination
so vaccines have been phenomenal in the last six months they offer a way to control this pandemic
we do have major challenges but we're starting to identify those and as ever staff in our College
have made a major contribution in this important global effort. Many thanks.