#14,186
Whenever we talk about a flu subtype - whether it be seasonal H3N2, or a novel H7N9 or H5N1 avian virus - we are really talking about a constantly evolving group of similar viruses, comprised of different clades, subclades, and variants.
Some subtypes are more stable than others, and in recent years seasonal H3N2 - which first emerged 51 years ago - has become increasingly diverse, and unpredictable.Illustrating how quickly things can change, last winter we saw the abrupt rise of H3N2 clade 3C.3a (see chart below) across the United States, which helped to turn what started out to be a mild H1N1 season into moderately severe mixed flu season.
All flu seasons bring with them a degree uncertainty, but the increased antigenic variety of viruses in circulation - particularly A/H3N2 - has complicated matters greatly for vaccine developers, who must decide 6 months in advance which strains to include.
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 an additional 30 days (see WHO: (Partial) Recommended Composition Of 2019-2020 Northern Hemisphere Flu Vaccine).
The problem was the sudden rise of H3N2 clade 3C.3a reported in the United States (and some other places). By February, this clade had exploded in the United States, 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.Today the ECDC has published their 8th Influenza Virus Characterization report of 2019, and it continues to show a highly complex array of H3N2 viruses, all competing for dominance along with increased diversity in seasonal H1N1 viruses as well.
Some excerpts from the lengthy report follow, but you'll want to download and review the full PDF to get all of the (highly technical) details.When you return, I'll have a postscript.
Influenza virus characterisation Summary Europe, June 2019
Summary
This is the eighth report for the 2018–19 influenza season. As of week 25/2019, 205 167 influenza detections across the WHO European Region had been reported. Detections were 98.9% type A viruses, with A(H1N1)pdm09 prevailing over A(H3N2), and 1.1% type B viruses, with 85 (58%) of 146 ascribed to a lineage being B/Yamagata-lineage.
Since the May 2019 characterisation report 1 , a further eight 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 1 373 virus specimens, with collection dates after 31 August 2018, have been received.
A number of the 69 A(H1N1)pdm09 test viruses characterised antigenically since the May 2019 characterisation report showed reduced reactivity, with antiserum raised against the 2018–19 vaccine virus, A/Michigan/45/2015 (clade 6B.1).
The 473 test viruses with collection dates from week 40/2018 genetically characterised at the WIC, including two H1N2 reassortants, have all fallen in a 6B.1 subclade, designated 6B.1A, defined by HA1 amino acid substitutions of S74R, S164T and I295V. Of these recently circulating viruses, 430 also have HA1 S183P substitution, often with additional substitutions in HA1 and/or HA2.
Since the last report, 36 A(H3N2) viruses successfully recovered had sufficient HA titre to allow antigenic characterisation by HI assay in the presence of oseltamivir; all were poorly recognised by antisera raised against the currently used vaccine virus, egg-propagated A/Singapore/INFIMH-16-0019/2016, in HI assays.
Of the 386 viruses with collection dates from week 40/2018 genetically characterised at the WIC, 315 were clade 3C.2a (with 38 3C.2a2, 14 3C.2a3, eight 3C.2a4 and 255 3C.2a1b); 71 were clade 3C.3a.
Five 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 a total of seven viruses characterised from EU/EEA countries this season, one has been Δ162-163 and six Δ162-164 (five African and one Asian subgroup).
Three B/Yamagata-lineage viruses have been characterised in this reporting period, bringing the total to 13 for the 2018–19 season. 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 which is recommended for use in quadrivalent vaccines for current and subsequent northern hemisphere influenza seasons.
(Continue . . . )
There are a number of caveats to this report, prime among them is this data represents influenza viruses collected in Europe last spring, and that is but a small sample of global flu activity.
While useful, it can't really tell us what kind of flu season to expect - or what subtypes (and clades) - will be dominant this fall, or in early 2020.The rapid rise of clade 3C.3a across the United States last winter shows just how quickly things can change. While there is much information in this 27 page report, we can cherry pick a couple of notable points.
First, seasonal H1N1 - which remained remarkably stable for the first 7 years following its emergence as a pandemic in 2009 - continues to show signs of increasing antigenic diversity.
Although a new vaccine virus was selected last February (A/Brisbane/02/2018 (H1N1)pdm09-like virus), today's report indicates its performance against this newly selected strain is lower than in the last report (see snippet below).
This may be related to a degree of antigenic drift as the viruses analysed over the last month have circulated more recently, with the majority having collection dates from 1 February 2019.
Loss of recognition was somewhat less with antiserum raised against A/Brisbane/02/2018, the vaccine virus recommended for the 2019–20 northern hemisphere influenza season [1]; 74% of test viruses were recognised at titres within twofold of the respective homologous titres and 96% within fourfold (Table 3-5), compared to 91% and 100% respectively in the May 2019 characterisation report.Whether this trend continues, or how much impact it will have on vaccine effectiveness (VE), is the $64 question. It is something to watch.
H3N2 remains as perplexing as ever, and so far - at least in Europe - they haven't seen the sort of rise in clade 3C.3a that the United States experienced last winter.
Of the 49 new H3N2 viruses added since the last report, only 7 (15%) were of this emerging clade, while 85% remain clade 3C.2a (with subclade 3C.2a1b showing the largest increase).Whether or not a clade 3C.3a vaccine match virus becomes the king of the viral hill globally this fall remains to be seen. 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.
Selecting vaccine viruses 6 months prior to the start of the flu season is always a bit of a gamble, but has become even more so as the antigenic diversity of co-circulating flu strains has increased.
The good news is there's evidence to suggest that an even 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.