#14,122
With the 2018-19 Northern Hemisphere flu season now over, we are already following what is shaping up to be a difficult 2019 Southern Hemisphere flu season, and looking ahead to the return of seasonal flu north of the equator next fall.
All flu seasons bring with them a degree uncertainty, but over the past few years the growing diversity of H3N2 viruses has added additional complexity to the twice annual selection of flu vaccine strains.So much so, that last February - when the WHO normally decides on what strains to put in next fall's vaccine - they opted to delay their decision on the H3N2 component for 30 days (see WHO: (Partial) Recommended Composition Of 2019-2020 Northern Hemisphere Flu Vaccine).
At issue was the sudden rise of H3N2 clade 3C.3a reported in the United States (and other places), which had started last fall's season as a minor component of what appeared on track to being a relatively mild H1N1 season.By January and February, H3N2 clade 3C.3a had exploded in the United States (see CDC chart below), and in late March the WHO placed their fall flu vaccine bet on this rising strain.
Every month during the Northern Hemisphere's flu season - and slightly less often over the summer - the ECDC publishes a review of recently isolated seasonal flu viruses collected across the EU in their Influenza Virus Characterization Report.
The hope is this can give us an early head's up on what virus strains are gaining ground, and are more likely to be a player in this fall's flu season.While we continue to see good (and reassuring) data on the stability of the H1N1 virus, H3N2 has - since 2014 - become increasingly difficult to analyze due to `. . . variable agglutination of red blood cells (RBCs) from guinea pigs, turkeys and humans, often with the loss of ability to agglutinate any of these RBCs.'
So much so, that only one of H3N2 samples submitted since the the last report was able to be analyzed, and it reacted poorly to the current vaccine virus (A/Singapore/INFIMH-16-0019/2016 (subclade 3C.2a1)).I've posted the ECDC summary below, along with a link to the far more detailed PDF document. I've have a brief postscript when you return.
Influenza virus characterisation, May 2019
Surveillance report
10 Jun 2019
Time period covered: May 2019
This is the seventh report for the 2018–19 influenza season. As of week 20 in 2019, 204 512 influenza detections across the WHO European Region have been reported. Ninety-nine per cent were type A viruses, with A(H1N1)pdm09 prevailing over A(H3N2), and 1% type B viruses, with 83 (60%) of 139 ascribed to a B/Yamagata-lineage.
Executive summary
Since the April 2019 characterisation report1, an additional four shipments of influenza-positive specimens from EU/EEA countries were received at the London WHO CC, the Francis Crick Worldwide Influenza Centre (WIC). A total of 1 184 virus specimens with collection dates after 31 August 2018 have been received.
Nine A(H1N1)pdm09 test viruses from Slovenia characterised antigenically since the April 2019 characterisation report all showed good reactivity with antiserum raised against the 2018–19 vaccine virus, A/Michigan/45/2015 (clade 6B.1). Four hundred test viruses with collection dates from week 40 of 2018 genetically characterised at the WIC, including an H1N2 reassortant, all fell in a 6B.1 subclade designated 6B.1A, defined by HA1 amino acid substitutions of S74R, S164T and I295V. Of these recently circulating viruses, 365 also had HA1 S183P substitution, often with additional substitutions in HA1 and/or HA2.
Since the last report, only one successfully recovered A(H3N2) virus had sufficient haemagglutinin (HA) titre to allow antigenic characterisation by haemagglutination inhibition (HI) assay in the presence of oseltamivir. The virus was poorly recognised by antisera raised against the currently used vaccine virus, egg-propagated A/Singapore/INFIMH-16-0019/2016, in HI assays. Of the 337 viruses with collection dates from week 40 of 2018 genetically characterised at the WIC, 273 were clade 3C.2a (with 32 3C.2a2, 13 3C.2a3, six 3C.2a4 and 222 3C.2a1b) and 64 were clade 3C.3a.
No B/Victoria-lineage viruses have been characterised in this reporting period. All recent viruses carry HA genes that fall in clade 1A, but encode HA1 amino acid substitutions of I117V, N129D and V146I compared to a previous vaccine virus, B/Brisbane/60/2008. Groups of viruses defined by deletions of two [Δ162–163, 1A(Δ2)] or three [Δ162–164, 1A(Δ3)] amino acids in HA1 have emerged, with the triple deletion group having subgroups of Asian and African origin. HI analyses with panels of post-infection ferret antisera have shown these virus groups to be antigenically distinguishable. Of the five viruses characterised from EU/EEA countries this season, one has been Δ162–163 and four Δ162–164 (three African and one Asian subgroup).
No B/Yamagata-lineage viruses have been characterised in the reporting period. Eleven from the 2018–19 season have been characterised. All have HA genes that fall in clade 3 and encode HA1 amino acid substitutions of L172Q and M251V compared to the vaccine virus B/Phuket/3073/2013, but remain antigenically similar to the vaccine virus that is recommended for use in quadrivalent vaccines for current and subsequent northern hemisphere influenza seasons.
Download
Influenza virus characterisation, May 2019 - EN - [PDF-3.94 MB]
The H3N2 virus emerged as a pandemic strain in 1968 (supplanting seasonal H2N2), settling in the following year as a seasonal flu strain and remained the sole human influenza A strain until 1977, when H1N1 mysteriously reappeared after a 20 year absence.
Since then, H3N2 has co-circulated with (first) the old H1N1 strain (until 2009) and then the new H1N1pdm09 strain. Unlike in previous pandemics, the 2009 H1N1 virus did not supplant the existing (in this case, H3N2) influenza A virus.H3N2 is the longest continually circulating Influenza A virus on record. Over that time it has had to reinvent itself innumerable times (via antigenic drift) to evade acquired immunity, resulting in an growing variety of subclades of the virus jostling for dominance around the globe.
All of which makes vaccine selection - six months in advance of the next flu season - particularly challenging.The good news is that the flu shot's effectiveness against H1N1 and both Influenza B viruses has been reasonably good the past few years, and there's evidence to suggest that a less-than-perfectly matched flu vaccine may reduce the severity of one's illness (see CID Journal: Flu Vaccine Reduces Severe Outcomes in Hospitalized Patients).
Which means that come the fall, I'll be rolling up my sleeve again. Because I'd rather have some protection, rather than no protection, any day of the week.
