The future of influenza vaccines

Published on July 11, 2013   30 min

A selection of talks on Respiratory Diseases

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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.
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