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Universal Flu Vaccine: One step closer?

February 10, 2011

There have been stories in the news recently about the development of a vaccine that could protect against all strains of flu. I wanted to look at this research in a little more detail…

 

Current flu vaccine situation

Flu vaccines currently in production act to increase our body’s humoral immune response (this is the arm of the immune system that produces antibodies) to the influenza virus.

The flu virus has glycoproteins on its surface that are ‘visible’ to our immune system when the virus invades. Two particular glycoproteins – hemagglutinin (HA) and neuraminidase (NA) (from where we get the H and the N for the virus name, for example H1N1) – are especially important in our bodies’ recognition of the virus and it is the body’s antibody response to these glycoproteins that current vaccines boost. These two proteins can differ widely between strains, meaning that if we are exposed to a new strain with different proteins from the strain that we were exposed to either at vaccination or previous infection, our immune systems no longer recognise the virus as effectively, allowing it to multiply and cause ‘flu’.

The proteins are different between strains because of the processes of antigenic drift and antigenic shift. Antigenic drift is the more commonly occurring method of mutation and involves a minor change in the glycoprotein structure, for example a single amino acid change. This minor change can mean that the immune system of someone who has already been exposed to the virus may no longer be able to recognise it as efficiently, but they may still be partially protected. Antigenic shift is a much more major change in glycoprotein structure and occurs when the HA or NA from two different subtypes mixes to form an entirely new subtype. It is because of this high rate of mutation that different vaccines are needed every year.

Humans can be infected by three different types of influenza virus (A, B and C) with types A and B being the most common and we aren’t the only species that can be infected: wild birds, domestic poultry and pigs can all be infected by type A influenza. This can have potentially severe consequences because if, for example, a pig becomes infected with both a ‘bird type’ virus and a ‘human type’ virus and mixing occurs this can result in an antigenic shift producing a new virus that can infect humans, but which is so different from the original human strain that our immune systems don’t recognise it, making an entire population susceptible to it. This is when a pandemic can occur.

Vaccines can be made against a pandemic strain, but a new vaccine takes months to make and get into production, meaning that there are months when there is no vaccine available and people are susceptible to the virus allowing it to spread rapidly. If we could make one vaccine that produced an immune response that protected us from all strains of the virus, or at least all strains of influenza A and if it was widely used it would have the potential to prevent, or at least dramatically reduce the risk of pandemic outbreaks.

 

What they did

Researchers from The Jenner Institute at Oxford University conducted a Phase I clinical trial – this is where a new drug or vaccine is tested on a small number of healthy volunteers. The vaccine they were testing boosts the body’s immune response, not to surface antigens, but to antigens found inside the virus. These internal antigens are much more similar between strains than HA or NA. Rather than boosting an antibody response, the vaccine is designed to boost a cell-mediated response involving a subset of white blood cells called T cells.

The researchers injected the vaccine either intradermally (into the skin layers) or intramuscularly, monitored any side effects and measured T cell responses.

 

What they found

1) The vaccine is safe in healthy volunteers – a good start!
2) The vaccine boosts T cell responses – so the vaccine is at least having some effect on the immune system and it seems to be a beneficial one.

 

Caveat

We don’t yet know what level of T cell response is actually required to prevent disease. We won’t know how effective the vaccine is until the researchers complete their next stage: viral challenge studies. They will give healthy volunteers the vaccine and then infect them with influenza virus and monitor what happens.

If these future studies are successful and the vaccine does boost cross-reactive T cell responses it has the potential to reduce the level of illness in infected people and how much virus they shed regardless of strain even if the strain had the potential to cause a pandemic. This would be a fantastic break-through for public health.

Fingers crossed the next studies go well then!

 

Citations
Berthoud TK et al (2011). Potent CD8+ T-Cell Immunogenicity in Humans of a Novel Heterosuptypic Influenza A Vaccine, MVA-NP+M1. Clinical Infectious Diseases 52(1) 1-7. doi:10.1093/cid/ciq015

Chen J & Deng Y-M. (2009) Influenza virus antigenic variation, host antibody production and new approach to control epidemics. Virology Journal 6. 30 doi: 10.1186/1743-422X-6-30

Liang S et al (1994). Heterosubtypic Immunity to Influenza Type A Virus in Mice. Journal of Immunology 152. 1653

Health Protection Agency

Oxford JS (2000). Influenza A pandemics of the 20th century with special reference to 1918: virology, pathology and epidemiology. Reviews in Medical Virology 10(2). 119-133 doi: 10.1002/(SICI)1099-1654(200003/04)10:23.0.CO;2-O

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