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I'm Professor Marc Girard.
I used to be professor at
University of Paris Diderot,
but I'm retired now.
I also was Professor at
the Pasteur Institute,
where I spent most of my career.
Now, I'm at the French
National Academy of Medicine.
I'm going to speak
of the future of
influenza vaccines,
novel vaccines,
and especially the
possibility of
developing what we call the
universal influenza vaccine,
which would cover all virus
strains and would not be
subjected to yearly
rearrangements
and modification of the strains,
as is done today for what we
call the seasonal vaccine.
We'll see all of this.
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This first slide shows you, in
a diagrammatic manner, what
the influenza virus
looks like and what
are its principal antigens.
The virus is an RNA virus.
It is an envelope.
That is to say that
it is surrounded by
a lipid membrane
which is depicted on
this scheme at left
by this red layer,
and this lipid layer is
spiked by a series of
viral proteins which are
illustrated here as
these yellow peaks,
which is the hemagglutinin, HA,
with these blue balloons,
neuraminidase, NA,
these are the two most
important antigens
on the surface of
the virus and these
are the basis
of the current vaccine
against influenza.
Now this lipid membrane
is wrapped around
a shell made by
proteins, the M1 protein
that you see on the left.
M1 protein is a viral
protein also called
metrics and therefore
makes the viral particle tight.
It however contains a few holes
or other channels
which are made of
another viral protein
metrics protein M2
which makes the inside of
the virus communicate
with the outside.
Inside the virus particle
is these pearls, that
you see on the graph,
which are made of
the nucleoprotein,
NP and the nucleoprotein is
wrapped around the RNA
genome of the virus,
which as you know is made of
eight different RNA
segments and these are
all surrounded by
the nucleoprotein
and all tightly packed
inside the virus particle.
On the right-hand
side of the slide,
you see the X-ray
crystallography,
a real range color of the
hemagglutinin molecule.
It's made actually of two parts.
There is a global head and a
long stem which goes inside
the membrane and
this corresponds to
2HA subunits, HA1 and HA2.
The globular head depicted
here in blue and red and
green contains the
receptor binding pocket,
illustrated in green here,
which allows the
molecule to grab
the virus receptor on the
surface of permissive cells.
This is very important because
it allows the virus to
penetrate eventually
into the cell
where it will replicate.
This also is the way by which
a virus can be virulent
or non-virulent,
because depending upon the
specificity of the receptor,
you can have avian receptors,
mammalian receptors.
Receptors in the upper
respiratory tract are not the
same as the receptor
in the lung and this
explains a lot about the way
these viruses can be specialized
in an animal species
and be transmitted or
not transmitted to
humans or not transmitted
from humans to humans.
The bottom part of the
molecule, the HA2 part,
which anchors the HA spike
into the lipid membrane,
which we also call
the stem contains, as
depicted here in yellow,
a conserved region,
which is very important because
it will elicit antibodies,
which will recognize
a wide variety
of different influenza
virus strains.
I will briefly review what are
