Friday, July 24, 2020

ECDC: Influenza virus characterisation - Summary Europe, June 2020




#15,377

One of the biggest challenges with designing an influenza vaccine every year is that decisions must be made six months in advance (February in the Northern Hemisphere, September in the Southern) about  which virus strains to include in the next season's vaccine. 

Complicating matters, while there are currently only two Influenza A subtypes (H1N1 & H3N2), and two Influenza B lineages (Victoria & Yamagata), each has multiple clades and/or variants circulating - and constantly evolving - around the world.

Generally speaking, over the past decade H1N1 has evolved more slowly than H3N2, and is less diverse, while H3N2 has been the problem child (see The Enigmatic, Problematic H3N2 Influenza Virus) - drifting unpredictably - resulting in disappointing vaccine protection (see Eurosurveillance: Low 2016/17 Vaccine Effectiveness (VE) Among Elderly Hospitalized H3N2 Cases).

Although this year's flu vaccine formulation is already set in stone, we continue to monitor the spread and evolution of influenza viruses around the world, to see if any major changes have occurred in the panoply of viruses circulating around the globe.  

This year, with most public health resources focused on COVID-19, getting data on seasonal influenza (and other threats) has been difficult (see Forgotten Fronts & Global Blind Spots). The last two ECDC Influenza Characterisation Reports (May, and April) reported that no antigenic analysis of submitted flu samples has been conducted since March.

Yesterday the ECDC published their June Influenza Virus Characterisation Report, and for the first time in months, we have some antigenic analysis on recently submitted viruses.  These reports are highly technical - and are admittedly intended for influenza virologists and epidemiologists - but can provide some important insights for those of us at a lower pay grade. 

Not unexpectedly, H3N2 remains highly diverse globally, with clade 3C.3a dominant in Europe, but subgroup 3c.2a1b+T135KA/B dominating in the United States. The vast majority (52 of the 68) of the European viruses analyzed were reportedly well recognized by antiserum raised against egg-propagated A/Kansas/14/2017, the current (2019/2020) vaccine virus.

H1N1, which has  typically been far less volatile, showed a rise in poor reactivity to the 2019-2020 vaccine virus, jumping from 9% of samples reported last March to 22% (22 of 99) in this month's report.

Similarly, 25% of the (69) Influenza B/Victoria viruses tested were not well recognized by antiserum raised against the vaccine virus for last year's northern hemisphere influenza season. 

These are relatively small samples, taken from a limited geographic region, and all 3 (H1N1, H3N2, B/Victoria) viruses have been updated for the 2020-2021 fall vaccine.  We won't know how good of a match these vaccine viruses are for this year's flu season until early in 2021. 
We are always looking in a rear view mirror when it comes to virus surveillance, and the situation 2 or 3 months ago (as reflected by these reports) may not hold true today, much less six months from now.
The reality is, as influenza viruses become more antigenically diverse, the job of picking which virus to include in next season's flu vaccine will only become more difficult.

All of which makes the development of a`universal' flu vaccine (see J.I.D.: NIAID's Strategic Plan To Develop A Universal Flu Vaccine) of greater importance than ever. 
Credit NIAID

For now, this `holy grail' of influenza remains elusive, and is likely still years away.  The six months lead time required for vaccine manufacturing, and the unpredictability flu's evolution, means we continue to be vulnerable to being blindsided by rapidly spreading variants of seasonal flu. 

I've only posted the executive summary of yesterday's report, so if you are interested,  follow the link to download and read the full 31-page report.

Influenza virus characterisation - Summary Europe, June 2020
Surveillance report
23 Jul 2020
Publication series: Influenza Virus Characterisation
Time period covered: Week 40/2019 - week 25/2020 

ECDC’s influenza virus characterisation reports are published periodically and give an overview of circulating influenza viruses. They provide details on the current vaccine strains, summarise the development of the viruses since the last report, and closely follow the main developments for the ongoing influenza season. Virus characterisation reports are primarily intended for influenza virologists and epidemiologists.
Executive summary

This is the eighth report for the 2019–20 influenza season. As of week 25/2020, 164 883 influenza detections across the WHO European Region had been reported; 73% type A viruses, with A(H1N1)pdm09 prevailing over A(H3N2), and 27% type B viruses, with 4 479 (98%) of 4 568 ascribed to a lineage being B/Victoria.

Since the May 2020 characterisation report1, nine shipments of influenza-positive specimens from EU/EEA countries have been received at the London WHO CC, the Francis Crick Worldwide Influenza Centre (WIC). In total, 1 608 virus specimens, with collection dates after 31 August 2019, have been received.

Of the 99 A(H1N1)pdm09 viruses from EU/EEA countries characterised antigenically since the May report, 77 were well recognised by antisera raised against the 2019–20 vaccine virus, A/Brisbane/02/2018. Of those viruses, 22, that showed poor reactivity generally carried amino acid substitutions (notably N156K) in the HA1 150-loop region. The 397 EU/EEA test viruses with collection dates from week 40/2019 genetically characterised at the WIC have fallen within subclades of clade 6B.1A: 358 6B.1A5A, 29 6B.1A5B, 1 6B.1A6 and 9 6B.1A7.

The majority (52) of the 68 A(H3N2) viruses from EU/EEA countries characterised antigenically in June were clade 3C.3a and were well recognised by antiserum raised against egg-propagated A/Kansas/14/2017, the current vaccine virus. Globally, approximately equal proportions of clade 3C.3a and subgroups 3C.2a1b+T131K and 3C.2a1b+T135K viruses have been detected, but for viruses detected since 1 February 2020, subgroups 3c.2a1b+T135KA/B have prevailed in the USA while those of clade 3C.3a and subgroup 3C.2a1b+T131K have dominated in Europe. In total, 438 viruses from EU/EEA countries have been characterised genetically at the WIC: 245 clade 3C.3a, 126 3C.2a1b+T131K, 48 3C.2a1b+T135K-A and 19 3C.2a1b+T135K-B.

Sixty-nine B/Victoria-lineage viruses from EU/EEA countries were antigenically characterised in June, 63 subclade 1A(Δ3)B, one subclade 1A(Δ2) and five not sequenced. Approximately 25% of the subclade 1A(Δ3)B viruses were not recognised well by antiserum raised against B/Washington/02/2019, the vaccine virus for the 2020–2021 northern hemisphere influenza season. Poor recognition was generally associated with HA1 amino acid substitutions of either N126K or E128K. In total, 269 EU/EEA viruses have been characterised genetically at the WIC: 255 subclade 1A(Δ3)B and 14 subclade 1A(Δ2).

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Influenza virus characterisation - Summary Europe, June 2020 - EN - [PDF-2.74 MB]