Saturday, July 02, 2011

ECDC: Influenza Virological Summary May-June

 

 

 

# 5668

 

Although we talk about four main strains of influenza that circulate in humans (A/H1N1(pdm), A/H3N2, B Victoria, B Yamagata) – in reality there is a good deal more diversity in flu strains than that.

 

Influenza viruses are notoriously unstable, mutating at a rapid pace in order to evade acquired immunity. So it isn’t unusual to find numerous genetic variations within the same strain.

 

In fact, within the same host, you’ll find mutations occurring as the virus replicates. Most go nowhere, being unable to compete with its more `biologically fit’ parental viruses.

 

But occasionally a competitive strain emerges and crowds out the others, and under the right conditions, can be transmitted to others.

 

So over time, multiple variations of a virus strain end up circulating simultaneously.

 

Eventually, these mutations can move the virus far enough away from the original so that existing host defenses are no longer able to recognize it. That reduces (or eliminates) the immunity acquired by previous exposure or vaccination.

 

When a strain is said to be `antigenically similar’  to the vaccine strain, it is expected (but not assured) that the vaccine remains reasonably effective.  

 

But as these genetic changes accumulate, the effectiveness of a vaccine may eventually erode, and the vaccine strains must be replaced.

 

All of this is part of the normal evolution of influenza viruses, known as antigenic drift. It explains why it is necessary to re-evaluate, and change, the flu vaccine every year or two.

 

This constant reshuffling of influenza genes requires constant ongoing surveillance if vaccine manufacturers are to keep up with the virus. 

 

Which brings us to the latest ECDC influenza surveillance report for Europe. As you will see, there is a growing diversity in both the H1N1(pdm) and H3N2 virus strains.

 

First the abstract, and a link to the report:

 

Influenza virus characterisation, summary Europe, May-June 2011

Technical reports - 30 Jun 2011

 

image

ABSTRACT

Influenza A(H1N1)pdm, influenza A(H3N2), and influenza B/Victoria/2/87 lineage viruses have been characterised genetically and antigenically.

  • Recently isolated A(H1N1)pdm viruses continue to fall into several genetic groups but all groups show antigenic similarity to the currently recommended vaccine virus A/California/7/2009.
  • A(H3N2) viruses also continue to fall into distinct genetic groups with some viruses showing antigenic difference from the currently used vaccine virus A/Perth/16/2009, but there is no consistent correlation of altered antigenicity with any genetic group.
  • Influenza B viruses of the B/Victoria/2/87 lineage have predominated over those of the B/Yamagata/2/87 lineage. Most of the B/Victoria/2/87 lineage viruses are genetically and antigenically similar to the currently recommended vaccine virus B/Brisbane/60/2008.

 

 

After analyzing 450 virus samples submitted by EU countries between January and the end of May, the WHO reference laboratory in London has found the A/H1N1(pdm) strain has divided into 6 main genetic groups.

 

  1. N125D, observed originally as an emerging genetic group in the Southern Hemisphere and subsequently widespread in the Northern Hemisphere and exemplified by the reference virus A/Christchurch/16/2010;
  2. D97N and S185T, e.g. A/England/676/2010;
  3. S143G, S185T and A197T, e.g. A/Baden-Wurtemburg/14/2010 or A/Brussels/S0004/2011; 
  4. A134T and S183P, e.g. A/Alborz/5607/2010; 
  5. D97N, R205K, I216V and V249L, e.g. A/Trieste/11/2011;
  6. vi)  N31D, S162N (adding a glycosylation site) and A186T, e.g. A/Czech Republic/32/2011

 

These six groups are increased from four described last April. Despite this growing diversity, the report states:

 

The majority of viruses continue to react well with the panel of post-infection ferret antisera, including that raised against the vaccine virus A/California/7/2009.

 

Meaning that this fall’s vaccine is still expected to be effective against the bulk of these mutations.

 

The report shows the H3N2 (seasonal) strain has subdivided into 5 genetic groupings. The first 2 within the A/Perth/16/2009 clade, and the last 3 from the A/Victoria/208/2009  clade.

 

  1. I260M, R261Q, e.g. A/Victoria/210/2009 with some viruses also carrying the substitutions E50K and P162S, e.g. A/Hessen/5/2010;
  2. N133D (resulting in the loss of a glycosylation site), R142G, T212A, V213A, e.g. A/Norway/1330/2010
  3. N145S and V223I, e.g. A/Cote d’Ivoire/GR1678/2010 with some viruses having the substitution N144D that results in the loss of a glycosylation site, e.g. A/Paris/2120/2010; 
  4. N312S, e.g. A/England/270/2010, with many viruses also carrying T48A and K92R, e.g. the reference virus A/Rhode Island/01/2010;
  5. D53N, Y94H, I230V, E280A, e.g. the reference virus A/Alabama/05/2010, with some viruses also carrying the substitution S199A, e.g. A/Rheinland-Pfalz/7/2010.

 

There were a higher number of `low-reactor’ isolates among the H3N2 viruses, but all showed good reactions to A/Wisconsin/15/2009, a virus genetically and antigenically closely related to vaccine strain.

 

So while the data is a bit murkier on H3N2, there are reasons to believe the vaccine may still be largely effective against those strains as well.

 

And lastly, among the influenza B samples tested, 80% are a close match to the B/Victoria/2/87 lineage contained in this year’s vaccine.

 

Laboratory antigen characterization tests can give us an indication of how well a specific vaccine may protect against a virus strain, but they are not 100% predictive.

 

And admittedly, the viruses that were circulating in the spring may well be different by the fall.

 

It’s always a bit of a crap shoot when you have to pick just 3 influenza strains - 6 months in advance - to put in your vaccine.

 

While it may not be possible to cover all of the viral bases with a trivalent vaccine - despite these emerging strains - this year’s vaccine still looks to be a pretty good match for the bulk of the flu viruses now in circulation.