Tuesday, September 30, 2025

NPJ Vaccines: Effects of Repeated influenza Vaccination and Infection on Durable Seroprotection in Healthcare Workers

 

#18,891

I'll be rolling up my sleeve for my 20th consecutive seasonal flu shot next week, but I am keenly aware that there are some studies suggesting that with repeated flu vaccinations, comes the risk of mounting a diminished immune response.

This idea made headlines a decade ago (see Helen Branswell's report Getting a flu shot every year? More may not be better), following a preliminary report from Wisconsin’s Marshfield Clinic Research Foundation on the effectiveness of repeated flu vaccination in kids.
A similar report appeared earlier in the CMAJ (see Repeated flu shots may blunt effectiveness). However, these assumptions were based on limited data, during a time when the H3N2 subtype was undergoing rapid changes (see (CDC HAN Advisory On `Drifted’ H3N2 Seasonal Flu Virus).

Three years later (2018), the Marshfield Clinic released a follow-up report (below) which supported the receipt of the flu vaccine every year. 
Friday, October 26, 2018
A Marshfield Clinic Research Institute study recently found that getting a flu vaccination one year did not reduce vaccine effectiveness the next year in children, findings that support current recommendations for children to be vaccinated annually against influenza.

The study was conducted by Huong McLean, Ph.D., and Edward Belongia, M.D., of the Center for Clinical Epidemiology and Population Health at Marshfield Clinic Research Institute, and was published in JAMA Network Open.
(Continue . . . )
Also that year, in CMAJ Research: Repeated Flu Vaccinations Reduce Severity of Illness In Elderly, we looked at a study that found that repeated vaccinations over two or more years cut the rate of severe influenza illness in half.
In 2019, a systematic review of the literature (The impact of repeated vaccination on influenza vaccine effectiveness: a systematic review and meta-analysis) lent additional support to the idea of getting the flu vaccine every year, despite some decline in VE among people receiving back-to-back yearly flu vaccinations. 
Reassuringly, 2022's ISIRV: Immune Response From Repeated Seasonal Flu Vaccinations concluded: `Repeated vaccination provides similar or enhanced protection as compared with single vaccination in first-time vaccinees.'

Today we  have yet another study, which looked at 250 healthcare workers (median age ~38 &~78% female) from Norway over 4 consecutive (2010/11–2013/14) influenza seasons, who were divided into 4 cohorts based on vaccine receipt:
  • Current & Previous Vaccinated in the current season and previous season
  • Current Only Vaccinated in the current season but not the previous season
  • Previous Only Vaccinated in the previous season but skipped vaccination in the current
  • Unvaccinated Received no vaccine in either current or prior season
Participants were reclassified each year, depending upon vaccine receipt. All had previously received the AS03-adjuvanted pandemic A(H1N1)pdm09 vaccine in 2009. 

Key findings included:
  • Unvaccinated healthcare workers showed high influenza infection rates—up to 72% infected over just four seasons.
  • Vaccination significantly boosted protective antibody levels across all subtypes.
  • A/H1N1 immunity grew stronger with repeated vaccination; antibody durability improves after 3+ doses.
  • A/H3N2 immunity grew weaker with repeated vaccinations - with natural infection or hybrid immunity producing stronger protection.
  • While repeated A/H3N2 vaccination instilled some degree of seroprotective immunity (1) Antibody levels were significantly lower compared to H1N1, and (2) Protection waned more quickly compared to H1N1
This is a lengthy, detailed, and at time technical report, so I've only reproduced the abstract and some excerpts from the conclusion below. Follow the link for a deeper dive. 

I'll have a postscript after you return.
Published: 29 September 2025
Effects of repeated influenza vaccination and infection on durable seroprotection in healthcare workers
Rapid evolution of seasonal influenza viruses necessitates annual vaccine reformulation to match circulating strains. Healthcare workers (HCWs) and high-risk groups are prioritised for annual influenza vaccination. However, repeated annual vaccination may affect immune protection. This study investigated the hemaglutination-inhibition (HI) antibody responses following influenza infection or repeated seasonal vaccination over four seasons in 250 HCWs with well-defined vaccination histories.
Unvaccinated HCWs had high infection rates, with pre-existing antibodies providing protection. Infection or hybrid immunity generated higher antibody responses to A/H3N2 viruses than vaccination alone, whereas vaccination induced more durable A/H1N1 and B virus-specific antibodies. Vaccination boosted seroprotective antibodies, irrespective of previous vaccination histories. Moreover, repeated vaccination with the same virus for more than three consecutive seasons blunted antibody responses, while updating vaccine strains improved immunity.
Annual influenza vaccination of HCWs should be strengthened to increase uptake, but next-generation influenza vaccines must improve vaccine immunogenicity, particularly against A/H3N2 viruses.

        (SNIP)

In conclusion, seasonal influenza vaccination was effective in preventing influenza infection and boosting antibodies to above seroprotective levels in HCWs.

Repeated annual vaccination increased antibody persistence, which correlated with lower antibody responses to subsequent vaccinations. Repeated vaccinations with the same viruses more than thrice blunted antibody responses to vaccines, whereas updating the vaccine viruses likely improved antibody responses to vaccines

Our findings highlight the need to improve vaccine immunogenicity, particularly against A/H3N2 viruses, and demonstrate that repeated annual vaccination may have complex effects on antibody responses. More research is required to conclusively determine whether repeated annual vaccination has any negative effect on protection and the mechanism behind. 

We support continuing the current recommendation of annual influenza vaccination in HCWs. However, more refined vaccine strategies are essential to mitigate any potential negative effects of repeated vaccination while maintaining the benefits of seasonal vaccines.

While this is a single study, and it deals with a panoply of influenza viruses from nearly 15 years ago, it provides additional reassurance on the practice of getting an annual flu vaccine. 

It also reminds us that while `good', today's flu vaccines are not great. 

They don't protect as well, or as broadly, as we'd like. They are most useful in blunting the effects of infection, rather than preventing it (see CDC Hopes to `Reset' Flu Vaccine Expectations With New Campaign).

The human immune system is stunningly complex, and only partially understood. Individual responses to vaccination can vary depending upon age, health, and past (and first) influenza exposures (see Nature: Declan Butler On How Your First Bout Of Flu Leaves A Lasting Impression).
Add in rapidly evolving Influenza A viruses, with H3N2 being particularly labile (see The Enigmatic, Problematic H3N2 Influenza Virus), it is little wonder that decades of promises that a `universal flu vaccine' was close, have fallen short. 

But just as seatbelts don't guarantee you'll walk away unscathed from a collision, current seasonal flu vaccine can markedly reduce your chances of a severe infection. 

So, while we wait for a `better' vaccine solution - for me, at least - some protection is better than none. 

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Monday, September 29, 2025

Taiwan CDC Statement On Increased Antiviral Resistance in Seasonal H1N1 Cases in 2025

Credit NIAID

 #18,890

While spontaneous `resistance' to oseltamivir (aka `Tamiflu') develops in roughly 1%-2% of treated patients, for the past 18 months we've been watching a slow increase in the number of antiviral resistant H1N1 viruses around the world.

These resistant viruses, however, are generally thought to be less biologically `fit' than their susceptible counterparts, and are only rarely transmitted to others. 

Of course, that can always change - as we saw in 2008 - when in the course of a less than a year the (pre-pandemic) H1N1 virus defied all expectations and went from being 99% susceptible to oseltamivir to 99% resistant (see CIDRAP article With H1N1 resistance, CDC changes advice on flu drugs). 

While an influenza antiviral crisis seemed unavoidable, in an unlikely Deus Ex Machina moment a new swine-origin H1N1 virus - one that happened to retain its sensitivity to Tamiflu - swooped in as a pandemic strain in the spring of 2009, supplanting the older resistant H1N1 virus.

Since 2009 we've been closely watching for signs of increased antiviral resistance in seasonal flu - and while a few isolated pockets have occurred - none have established a foothold. 

But in March of 2024 we saw a worrisome report in The Lancet - Global Emergence of Neuraminidase Inhibitor-Resistant Influenza A(H1N1)pdm09 Viruses with I223V and S247N Mutations - which reported a much higher incidence of oseltamivir resistance among samples tested in Hong Kong in 2023.

Unlike the near total collapse of oseltamivir effectivess in 2008 - which was due to a an H275Y mutation in the NA - this was due to  I223V and S247N, and was not as profound of a loss in effectiveness. 

Four months later (see Viruses: Increase of Synergistic Secondary Antiviral Mutations in the Evolution of A(H1N1)pdm09 Influenza Virus Neuraminidases) researchers at the Robert Koch-Institute that reported seeing an uptick in permissive secondary mutations (NA-V241I and NA-N369K) in the NA or circulating H1N1 viruses that they believe may enable resistant strains to transmit more efficiently.

Earlier this summer we looked at a report from Spain which reported an increase in the number of the NA-S247N mutation in seasonal flu viruses collected in Spain over the 2023-2024 flu season (see Virus Research: A 15-year Study of Neuraminidase Mutations and the Increasing of S247N Mutation in Spain).

Today, Taiwan's CDC is responding to reports of a substantial increase in H1N1 resistant viruses in 2025.  While it doesn't report causitive genetic changes (e.g. H275Y or I223V S247N) - or the degree of resistance - it does report an incidence of 6.5% in 2025. 

Whether this is a localized fluke - or an early indication of  a trend - is to early to say.  Obviously we'll be watching for any similar reports as this year's flu season progresses.

I've posted a translation below.


The CDC responded to media reports about the emergence of resistance to influenza antiviral drugs, stating that the resistance rate is still low and limited to influenza A (H1N1). The current epidemic has shifted to influenza A (H3N2), and the impact is assessed to be limited. 
 
Release Date：2025-09-29 Regarding today's (29th) media report that a frontline physician group reported that "the incidence of resistance to oral and injectable influenza antiviral drugs has increased, resulting in a decrease in efficacy", the Centers for Disease Control (CDC) explained as follows:

1. According to CDC monitoring data, approximately 6.5% of the A H1N1 virus strains tested this year (2025) have resistance-related mutations to the oral antiviral drug Tamiflu or oseltamivir and the injectable antiviral drug Peramivir, which is slightly higher than last year (the statistics at the end of last year were 3.2%). No resistance to the above-mentioned drugs was detected in A H3N2 and B influenza virus strains this year. In addition, no resistance-related mutations were detected for the oral self-paid antiviral drug Baloxavir this year, regardless of A H1N1, A H3N2 or B influenza.

Second, the CDC assesses that the aforementioned drug resistance rate remains low and is limited to influenza A (H1N1). Furthermore, since entering the influenza season in Taiwan in September, the prevalence of community-circulating influenza viruses has recently shifted to influenza A (H3N2), which has not detected drug resistance (51.3% in the past four weeks, higher than influenza A (H1N1) at 43.4%), with the prevalence of influenza A (H1N1) continuing to decline.

Third, starting October 1st of this year, publicly funded influenza antiviral medication will be expanded to cover high-risk groups, in addition to the original year-round use. Anyone experiencing flu-like symptoms, after evaluation by a physician, can receive medication without rapid testing. Publicly funded influenza vaccination will also be available on the same day. The prevalent viruses have also shifted to influenza A (H3N2). The aforementioned drug resistance in some influenza A (H1N1) strains has limited impact on clinical treatment and epidemic control. The CDC will continue to closely monitor the prevalence of influenza strains and drug resistance, and will adjust relevant prevention and control strategies on a rolling basis.

The CDC once again reminds the public not to underestimate the severity of influenza. It is essential to maintain good respiratory hygiene and cough etiquette, including frequent hand washing. If you experience flu-like symptoms such as fever and cough, wear a mask and seek medical attention promptly. If you are sick, rest at home. For information on the use of publicly funded pharmacies, a list of contracted medical institutions, and influenza prevention and control information, please visit the CDC's global information website (https://www.cdc.gov.tw) or call the toll-free epidemic prevention hotline 1922 (or 0800-001922).
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Preprint: H5N1 Influenza A is Now Promiscuous in Host Range and Has Improved Replication in Mammals


Flu Virus binding to Receptor Cells – Credit CDC

#18,889

As humans, we like to believe that tomorrow will be pretty much like today, or the day before (aka the `Normalcy Bias '). We tend to discount bad things happening in the future in favor of enjoying more immediate rewards.

So we put on blinders, or simply procrastinate, thinking we have plenty of time to prepare for future threats.  

In the 5 years prior to the emergence of COVID, the world was warned repeatedly about our continued lack of preparedness for a severe pandemic. While I could cite dozens of examples, a few include:
    • only just over half (n=104, or 54%) of member states responded. And of those, just 92 stated they had a national pandemic plan. Nearly half (48%) of those plans were created prior to the 2009 pandemic, and have not been updated since.
We even saw repeated warnings about our lack of adequate reserve ventilators (see 2017's Pandemic Realities: Ventilator Shortages) and a our disasterously low supply of PPEs (see 2009's Caught With Our Masks Down). 

While governments, agencies, and health organizations all promised remedial action - when COVID finally emerged in January of 2020 - it was obvious that far too little had been done to prepare. 

Today we find ourselves watching another virus (HPAI H5Nx) which circulates in many genetically distinct forms (subclades, subtypes, genotypes, variants, etc.) around the globe; one that has the potential of being even more impactful than SARS-CoV-2. 

While we see new warnings almost daily from scientists (see here, here, here, here, . . .  ad nauseum), few appear to be listening (see Two Surveys (UK & U.S.) Illustrating The Public's Lack of Concern Over Avian Flu). 

Today we've yet another cautionary report - this time from the University of North Carolina - which argues that contemporary clade 2.3.4.4b H5N1 viruses have undergone a functional shift - from being primarily avian-adapted - to actively evolving in mammalian hosts as well.

They cite both explosive spread and changing seasonality since H5's arrival in late 2021, and the emergence of two mammalian-linked linages: 

  • B3.13 in cattle (with spillovers into humans, cats, and other mammals)
  • and D1.x in wild birds, and poultry (with spillover into humans)
While historically H5Nx binds preferentially to α2,3-linked sialic acid found in the gastrointestinal tract of birds, some recent  H5N1 variants have shown markers for equally binding to α2,6-linked receptor cells, commonly found in (human & mammalian) upper airways. 

Add in PB2 mutations (E249K/G/D/V, E627K/V, I463M/V, V344M, A588T/V) which are associated with mammalian adaptation, and scattered reports of antiviral resistance (see Emerg. Microbes & Inf: Oseltamivir Resistant H5N1 (Genotype D1.1) found On 8 Canadian Poultry Farms), and you have a worrisome trend. 

The following report is both lenghty and at times technical.  It is computational analysis based on existing data, which - as we know - hasn't always been robust or released in a timely fashion.  

Despite its limitations, it paints a picture of a family of viruses that are actively evolving towards becoming a greater mammalian threat. 

I've only posted the abstract and a couple of excerpts.  Follow the link to read it in its entirety.   I'll have a brief postscript after you return.

H5N1 Influenza A is now promiscuous in host range and has improved replication in mammals
Sayal Guirales-Medrano, Kary Ocaña, Khaled Obeid, Rachel Alexander, Colby T Ford, Daniel Janies
doi: https://doi.org/10.1101/2025.03.15.641219
This article is a preprint and has not been certified by peer review

Preview PDF

Abstract

Influenza A virus has been circulating in birds from Eurasia for more than 146 years, but human infection has been sporadic. H5N1 (clade 2.3.4.4b) has recently infected hundreds of species of wild and domestic birds and mammals in North America. Infections include 70 people with two fatalities. We have developed an analytical bioinformatics, genomics, and structural workflow to understand better how H5N1 is circulating in North America and adapting to new host species. 

Our time-series analysis reveals that the circulation of H5N1 (clade 2.3.4.4b) in North America follows a distinct annual pattern, with cases in the United States consistently peaking each December. Separate from this seasonal cycle, our analysis also documents an increase in the total number of cases reported since 2021. 

We also show that H5N1 (clade 2.3.4.4b) spreads in North America as two distinct subclades of interest for human and animal health. These viral lineages have achieved a vast host range by efficiently binding the viral surface protein Hemagglutinin to both mammalian and avian cell surface receptors. 

This novel promiscuity of host range is concomitant with the additional strengthening of the Polymerase basic 2 viral proteins' binding for mammalian and avian immune proteins. Once bound, the immune proteins will have diminished ability to fight the virus, thus allowing for more efficient replication of H5N1 in mammalian and avian cells than seen in the recent past. 

Finally, structural docking analyses predict that while most current antivirals remain effective, a fatal human isolate showed significantly reduced binding to multiple drugs from different classes.

In conclusion, the H5N1 virus is causing an animal pandemic through promiscuity of host rage and strengthening ability to evade the innate immune systems of both mammalian and avian cells.

        (SNIP)

Conclusion

Our results indicate that HA has achieved broad receptor-binding capability on both avian and mammalian cells, Moreover, we find that PB2 is undergoing adaptive changes that enhance innate immune evasion and replication in avian and mammalian hosts. This showcases the importance of monitoring both HA and PB2 in emerging influenza strains to assess their potential for human adaptation.

Our antiviral selection findings provide a mixed but largely reassuring picture regarding the potential for antiviral resistance in circulating H5N1 strains. While the virus continues to evolve in other regions of the proteins that are the main targets for current antivirals, our analysis did not identify positive selection at the primary amino acid sites known to be associated with resistance to the most widely used influenza antivirals.

Future research integrating structural modeling with functional assays will be crucial for validating these computational predictions and improving our understanding of influenza A H5N1 host adaptation mechanisms and potential therapeutics (14).

Limitations

This study has limitations inherent to its computational nature. Our  findings on binding affinity and selection are predictive and require empirical validation through in-vitro and in-vivo experiments. Furthermore, while we analyzed two key genes, HA and PB2, viral adaptation is a complex process involving the entire genome.

Nevertheless, the workflow we have established—moving from large-scale phylogenetics to targeted structural biology—is a powerful tool for modern molecular disease surveillance. As sequence data becomes available, this approach can be rapidly deployed to assess new viral variants, providing early warnings and guiding public health responses before a crisis escalates.

        (Continue . . . )


None of this tells us how close H5Nx is to becoming a pandemic threat, of course.  There may even still be some species barriers that prevents that, although many seem to be falling by the wayside. 

But the many flavors of HPAI H5 make up just a small fraction of the viruses, bacteria, fungi, and parasites that have pandemic potential (see 2024 WHO Pathogens Priortization Report).

The question isn't whether HPAI H5 will spark the next pandemic, or when that might happen. Neither are knowable. But we do know that pandemics are inevitable, and appear to be occuring more frequently. 

The only question worth asking is: when the next one arrives, will be ready?

Or will we sleepwalk into the next global health crisis as unprepared as we did with the last one.

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Sunday, September 28, 2025

Sci. Adv.: PB2 and NP of North American H5N1 Virus Drive Immune Cell Replication and Systemic Infections



#18,888

While the HPAI H5N1 clade 2.3.4.4b virus currently circulating in the United States is a direct decendent of the Eurasian H5N1 strain, it quickly became genetically distinct due to constant reassortment with North American avian viruses (see Rapid Evolution of A(H5N1) Influenza Viruses After Intercontinental Spread to North America).

As a result, we've seen far more mammalian spillovers, especially to livestock, than have been reported elsewhere, and infected cats and other peridomestic mammals have often shown systemic infection and profound neurological manifestations. 
 
The chart above (from today's study) shows a pair of mutations (PB2 478I and NP 450N) remains rare in the Eurasian lineage (left/blue) but has become nearly fixed in the American lineage (right/red).
While these aren't the only differences, these mutations appear to significantly increase viral polymerase activity, resulting in enhanced replication efficiency in mammals.

 There are obviously other mutations of concern we are watching, including:

But today's study focuses on the tag-team of PB2 478I and NP 450N which appear to be doing much of the heavy lifting when it comes to mammalian spillovers of the H5N1 virus in North America.

This is a lengthy, detailed, and highly technical research article, most of which is primarily of interest to virologists. Those wanting full details will want to follow the link to read it in its entirety.

But briefly:
  • This paper identifies two mutations (PB2 478I and NP 450N) as critical for the virus’s enhanced replication, systemic dissemination, neuroinvasion, and unusually high mortality in ferrets. 
  • Using reverse genetics they found that reverting either mutation to the Eurasian-type in a North American virus resulted in attenuation: replication efficiency droped, systemic spread was blocked, and infected animals survived without severe disease.
  • These researchers cite PB2 478I and NP 450N as urgent targets for surveillance in North American and transboundary H5N1 outbreaks

First, the link, abstract, and a few excerpts from the study, after which I'll have a brief postscript.

PB2 and NP of North American H5N1 virus drive immune cell replication and systemic infections
Young-Il Kim , Seung-Gyu Jang , Woohyun Kwon, Jaemoo Kim , Dongbin Park , Isaac Choi , Jeong Ho Choi , Juryeon Gil , Mina Yu , [...] , and Young Ki Choi +11 authors Authors Info & Affiliations
Science Advances
26 Sep 2025
Vol 11, Issue 39
DOI: 10.1126/sciadv.ady1208

Abstract

The 2022 North American outbreak of 2.3.4.4b H5N1 avian influenza virus revealed substantial mammalian adaptation and pathogenicity, yet mechanisms remain unclear.
To address this knowledge gap, we investigated the North American H5N1 strain (GA/W22-145E/22), which demonstrated unique immune cell–mediated systemic dissemination, neuroinvasion, and 100% mortality in ferrets, unlike the nonlethal Eurasian strain (KR/W811/21).
Genomic and reverse genetics studies identified PB2478I and NP450N mutations as key determinants of enhanced polymerase activity, immune cell tropism, and pathogenicity.
Mutant GA/W22-145E/22 virus carrying PB2478V/NP450S showed complete survival without systemic dissemination. Furthermore, GA/W22-145E/22 demonstrated robust replication in human peripheral blood mononuclear cells and bovine mammary gland organoids, raising concerns about zoonotic spillover.
These findings underscore PB2478I and NP450N as pivotal markers of pathogenicity, emphasizing the urgent need for enhanced surveillance and targeted interventions.

        (SNIP)

In summary, we identify PB2478I and NP450N as key molecular determinants of virulence in the GA/W22-145E/22 strain. These mutations drive immune cell–mediated systemic spread, neuroinvasion, and potential vertical transmission.

Our findings highlight the evolving pathogenic landscape of NAm clade 2.3.4.4b H5N1 viruses and underscore the urgent need for active surveillance, preparedness, and targeted interventions to mitigate zoonotic and pandemic threats.

        (Continue . . .)

While the reporting of new cases, and outbreaks, has plummeted over the past 6 months - and the situation looks better `on paper' - the HPAI problem has not gone away. 

Last March we saw the average time to submit sequences to GISAID was 7 months, with some countries taking more than twice that. Many countries remain slow to share outbreak information, and some appear to be burying `bad news' completely (see From Here To Impunity).

As we've seen a hundred times before, this paper notes `. . . the urgent need for active surveillance, preparedness, and targeted interventions', but substantive action - if any - has been coming at a glacial pace. 

HPAI H5 is not a single threat, it is a collection of hundreds of related - but genetically distinct viruses - all of which are on their own evolutionary path. 
As they spread globally they reassort with new viruses - and spillover into new hosts - which affords them fresh opportunities to evolve and adapt. Yet the world continues to HPAI H5 as more of an economic or political concern, than as a potential public health threat. 

And while that may be true today, it could abruptly change with little warning.
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Saturday, September 27, 2025

WHO Recommendations for Influenza Vaccine Composition for the 2026 Southern Hemisphere Influenza Season

 

Credit ACIP

#18,887

Twice each year international influenza experts meet to discuss recent developments in human and animal influenza viruses around the world, and to decide on the composition of the next influenza season’s flu vaccine. Due to the time it takes to manufacture and distribute a vaccine, decisions on which strains to include must be made six months in advance.

Which means the composition of the northern hemisphere’s vaccine must be decided upon in February of each year, while decisions on the southern hemisphere’ vaccine are made in September.
Yesterday the WHO released their recommendations for the composition of next year's (2026) Southern Hemisphere flu vaccine, which notably include updates for both the H1N1 and H3N2 components.

Australia has recently come off a particularly rough flu season (see Ian Mackay's A Flunami in July), and just three days ago the MMWR published a review of the interim effectiveness of this year's Southern Hemisphere Flu vaccine (excerpt below).
During the 2025 Southern Hemisphere influenza season, seasonal influenza vaccination reduced influenza-associated outpatient visits by 50.4% and hospitalization by 49.7%.

A respectable, if not spectacular, result. 

But the WHO obviously sees evolutionary changes accuring in both H1N1 and H3N2, hence the tweak in next year's vaccine.  

Next Feburary, when it comes time to formulate next year's Northern Hemisphere's vaccine, we'll hopefully have even more data.  With influenza, the only constant is change. 

First, the press release from the WHO, after which I'll have a bit more.
Recommendations announced for influenza vaccine composition for the 2026 southern hemisphere influenza season
26 September 2025
 
The World Health Organization (WHO) today announced its recommendations for the viral composition of influenza vaccines for use in the 2026 influenza season in the southern hemisphere. The announcement was made at an Information Meeting after a 4-day Consultation on the Composition of Influenza Virus Vaccines.

Given the constantly evolving nature of influenza viruses, regular updates to vaccine composition are essential to ensure their effectiveness and to protect public health worldwide.

WHO convenes these consultations twice annually – once for the southern hemisphere and once for the northern hemisphere, bringing together an advisory group of experts from WHO Collaborating Centres and Essential Regulatory Laboratories. The group reviews surveillance and other data provided by the WHO Global Influenza Surveillance and Response System (GISRS) and collaborators to inform its recommendations.

WHO’s recommendations serve as the basis for national and regional regulatory authorities, pharmaceutical manufacturers, and other stakeholders to develop, produce, and license influenza vaccines for the upcoming season.

WHO recommends that trivalent vaccines for use in the 2026 southern hemisphere influenza season contain the following:

Egg-based vaccines
  • an A/Missouri/11/2025 (H1N1)pdm09-like virus;
  • an A/Singapore/GP20238/2024 (H3N2)-like virus; and
  • a B/Austria/1359417/2021 (B/Victoria lineage)-like virus.
Cell culture-, recombinant protein- or nucleic acid-based vaccines
  • an A/Missouri/11/2025 (H1N1)pdm09-like virus;
  • an A/Sydney/1359/2024 (H3N2)-like virus; and
  • a B/Austria/1359417/2021 (B/Victoria lineage)-like virus
Consistent with the four previous WHO recommendations since September 2023, it remains the opinion of the WHO influenza vaccine composition advisory committee that the inclusion of a B/Yamagata lineage antigen is no longer warranted.

Quadrivalent vaccines, where the transition to trivalent vaccines is not yet complete, contain a 4th component – a B/Yamagata lineage virus (B/Phuket/3073/2013-like virus).

There will no longer be updated recommendations for the B/Yamagata lineage component.

WHO has also updated recommendations for the development of new candidate vaccine viruses for zoonotic influenza, with a view on pandemic preparedness.

We've just come off one of the most impactful flu seasons in 15 years, which was characterized in the CDC's MMWR  two weeks ago. 

Seasonal flu vaccine uptake in the United States peaked in 2019, and has begun a slow, but steady decline since.


Pandemic fatigue, plus growing anti-vaccination sentiment, and admittedly lackluster protection against influenza infection have all had some impact.

Flu vaccines, however, do a much better job reducing the severity of infection, and thereby reducing hospitalizations and death (see (ESR) Influenza Vaccine Outcomes: A Meta-Analysis Revealing Morbidity Benefits Amid Low Infection Prevention).

And the more we learn about influenza's extra-pulmonary impacts on the body (see Risk of Cardiovascular Events After Influenza: A Population-based Self Controlled Case Series Study) the more important protecting yourself becomes. 

Although we've no way of knowing what this fall/winter's flu season will bring, the flu vaccine still remains one of the most effective ways to reduce your risk of severe disease from the influenza virus. 
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Friday, September 26, 2025

L.A. County Public Animal Health Alert: Another H5N1 Domestic Cat Cluster Linked To Raw Cat Food

 


#18,886

Last January - after a number of reports of domestic cats sickened or dying from raw (H5N1 contaminated) cat food (see here, here and here)  - the US FDA Issued New Requirements For Pet Food Manufacturers - APHIS Updates Turkey Surveillance Policies - although it left the corrective steps largely up to the manufacturers (see snippet below).
Under the PCAF requirements, animal food businesses must conduct a reanalysis of their food safety plan when the FDA determines it is necessary to respond to new hazards and developments in scientific understanding.

Over the past 9 months we've continue to see reports of pets infected, or dying, from H5N1 contaminated cat food around the country (see here, here, here, and here), including earlier this month in San Francisco (see FDA Issues New Warning On H5N1 Detected In Cat Food).

Despite warnings from veterinarians, and public health officials, of the dangers of feeding pets a raw food diet (see FDA Get the Facts! Raw Pet Food Diets can be Dangerous to You and Your Pet), these products remain on the shelf, and people continue to buy them.

Sadly, today we have another alert from Los Angeles County, which describes the deaths of 2 indoor cats who were fed raw commercial pet food; one of which tested positive for the bovine B3.13 genotype of H5N1.  

While they state the FDA is investigating, the brand, and lot number of the suspected source was not provided. 

Raw pet food not only endangers the pet, but also potentially those who live in close contact with these pets (see CDC advice for pet owners), or those handling the food. 

Some excerpts from yesterday's Los Angeles Animal Health Alert (for veterinarians) follow:

Animal Health Alert: H5 Bird Flu confirmed in Los Angeles County in another domestic cat that consumed commercially available raw pet food

Key Points:

  • Highly Pathogenic Avian Influenza (HPAI) A(H5N1) aka H5 bird flu, has again been confirmed in a local cat. This is the first reported case in a cat since the cluster (9 confirmed and 10 suspected cases) that were infected via raw milk, raw pet food, and raw meat in December 2024–January 2025. 

  • Two indoor-only cats from a single household became acutely ill and died after consuming commercially available raw pet food. One cat tested positive for H5N1(clade 2.3.4.4b genotype B3.13). The second cat was not available for testing. 

  • Investigation into the raw food product consumed by these cats is ongoing with the FDA.

  • H5 bird flu continues to circulate in the U.S.

  • Always take dietary and exposure histories. Specifically note any feeding of raw pet food, raw milk, raw meat, or food or treats that are freeze dried without cooking first. Ask pet owners about pet access to and predation of wild birds.

  • Isolate suspected cases of influenza in pets, wear appropriate personal protective equipment (PPE) and practice thorough cleaning and disinfection. There may be risk of transmission to other pets through direct transmission or contaminated fomites. 

  • REPORT suspected cases of H5 bird flu in cats and other animals in Los Angeles County to Veterinary Public Health. Free testing for influenza in a pet may be available. Criteria for free testing can be found below.

Dear Veterinary Colleagues: 

Approximately 1-2 weeks after beginning to consume a batch of commercially available raw pet food purchased in Los Angeles County, one cat in a household of two strictly indoor-only cats became acutely ill. This cat had signs of inappetence followed by a rapid decline characterized by neurologic symptoms. The cat died several days after the initial signs of illness. About five days after the first cat became ill, the second cat showed signs of illness including a loss of appetite and fever that progressed to severe neurologic signs before this cat also died. This second cat was sampled for influenza A by PCR testing on swabs of the nares, oropharynx and rectum after its death. The samples were tested by the Los Angeles County Public Health Laboratory and all three were PCR-positive for influenza A. The sample was then confirmed positive for H5N1 avian influenza clade 2.3.4.4b genotype B3.13 on September 23, 2025, by the USDA’s National Veterinary Services Laboratory (NVSL). This is the genotype currently circulating in dairy cows and poultry in the U.S. The NVSL will also analyze the samples using whole genome sequencing (WGS).

The owner identified the raw food product that was fed to the cats and shared the packaging and lot code information. Investigation into the food is ongoing with the U.S. Food and Drug Administration (FDA).

LAC DPH is monitoring household members and veterinary clinic staff who had contact with the sick cats for flu symptoms and offering testing and treatment for persons with clinical signs. No human cases of H5 bird flu have been linked to this case to date, and the risk of virus transmission to people remains low.

Veterinary Public Health extends sincere condolences to the family of these cats. We sincerely appreciate the time and effort by the pet owners who provided information about their household pets, exposures and about the raw products their cats consumed. Reporting unusual occurrences of animal disease is critical to protecting the health of both animals and people in Los Angeles County.

H5 Bird Flu Situation 

The H5 bird flu virus continues to cause a severe panzootic. Traditionally it primarily infects poultry and other birds, but it has also been detected in livestock (mainly dairy cattle) and other wild and domestic mammals in the U.S., as well as in at least 74 species of mammals worldwide. It continues to be detected in birds and mammals in multiple regions around the world including in both polar regions. This large range of infected animal species worldwide highlights the potential for the virus to mutate and become more transmissible among animals, including humans. To date there have been 70 confirmed human cases in the U.S. including one death from H5 bird flu.

H5 bird flu is a One Health issue that significantly affects human health, animal health and environmental health. With this strong scientific evidence of the linkage between contaminated raw products and cats developing severe or fatal H5 bird flu infection, veterinarians should strongly advise pet owners to not consume nor feed raw dairy, raw meat, raw poultry, and raw pet food diets to pets. 

Cat-to-cat transmission of H5 bird flu has been demonstrated experimentally and may occur in cats that are in close contact. A recently published case of H5 Bird flu in an immunocompromised cat may have been caused by fomites contaminated by another illcat in a veterinary practice.

The risk of cat-to-human or human-to-human spread of H5 bird flu, and the risk to the general public continues to be very low. However, people who come into close contact with animals, especially wild birds and their feces, infected cats, infected poultry, or infected dairy cattle or their milk, have a greater risk of exposure. It is important to take proper precautions, as described below. 

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While survivable with early and aggressive treatment, H5N1 is a particularly virulent (and often deadly) infection in felines.  Dogs are susceptible, but appear to experience less severe (sometimes subclinical) illness. 

Spillovers into companion animals are particularly worrisome because of the potential for spreading to other animals, or to humans (see JAVMA: Companion Animals and H5N1 Highly Pathogenic Avian Influenza: Cause for Concern?).

Why we are still feeding cats raw food is a mystery to me.  But there is probably some truth to the adage that you can only poke the bear so many times before you get mauled.  

A few, of many studies on outbreaks in cats include:

Virology: Highly Pathogenic Avian Influenza A H5N1 Virus Infection in an Immunocompromised Domestic Cat

Viruses: The Seroprevalence of Influenza A Virus Infections in Polish Cats During a Feline H5N1 Influenza Outbreak in 2023

CDC MMWR: HPAI H5N1 Virus Infection of Indoor Domestic Cats Within Dairy Industry Worker Households — Michigan, May 2024

Emerg. Microbes & Inf.: Marked Neurotropism and Potential Adaptation of H5N1 Clade 2.3.4.4.b Virus in Naturally Infected Domestic Cats

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CDC MMWR x 2: Record Pediatric Flu Deaths & Pediatric Influenza-Associated Encephalopathy and Acute Necrotizing Encephalopathy

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Although the 2024-2025 flu season hasn't quite ended, last winter's influenza-related hospitalizations are reportedly the highest in nearly 15 years (see MMWR: Influenza-Associated Hospitalizations During a High Severity Season (United States, 2024–25),

A particularly painful subset of these severe cases were pediatric - and while likely an undercount - the CDC reports 280 pediatric flu related deaths over the past 12 months; the highest total since the 2009-2010 pandemic. 

 

Yesterday the CDC's MMWR published 2 reviews of our current flu season; on pediatric deaths and influenza-related encephalopathy (including ANE).  Both of which were likely exacerbated by a reduced uptake of the seasonal flu vaccine, and the underuse of influenza antivirals. 

In the past (see Neuroinfluenza: A Review Of Recently Published Studies), severe neurological presentation from influenza infection was thought to be `rare', but in recent years we've seen indications that its incidence may be rising. 

The CDC's MMWR describes IAE and ANE as:

Influenza-associated encephalopathy (IAE), a recognized complication of influenza, refers to neurologic syndromes triggered by influenza virus infection of the respiratory tract, resulting in a dysregulated host inflammatory response and leading to varying degrees of brain dysfunction (1,2).
One of the most severe forms of IAE is acute necrotizing encephalopathy (ANE), a condition that disproportionately affects children and is characterized by rapid neurologic decline and neuroimaging with evidence of necrosis or hemorrhage involving the thalami; ANE has a poor prognosis and can result in lasting neurologic sequelae or death (2,3).

While you'll want to follow the links to read both reports in their entirety, a brief overview of yesterday's two MMWR reports follow.  I'll have a postscript after the break. 


Influenza-Associated Pediatric Deaths — United States, 2024–25 Influenza Season
Weekly / September 25, 2025 / 74(36);565–569
 
Katie Reinhart, PhD1; Stacy Huang, MPH1; Krista Kniss, MPH1; Carrie Reed, DSc1; Alicia Budd, MPH1 (VIEW AUTHOR AFFILIATIONS)View suggested citation

Summary

What is already known about this topic?

Influenza can cause severe illness and death among all persons, including children.

What is added by this report?

The 2024–25 influenza season had the highest number of pediatric deaths reported (280) since child deaths became nationally notifiable in 2004, except for the 2009–10 influenza A(H1N1)pdm09 pandemic. Approximately one half of children who died from influenza had an underlying medical condition, and 89% were not fully vaccinated.

What are the implications for public health practice?

All persons aged ≥6 months who do not have contraindications should receive an annual influenza vaccination to prevent influenza and its complications, including influenza-associated death.
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Full Issue PDF

Abstract

Influenza-associated deaths among children aged <18 years have been nationally notifiable since 2004. The highest number of pediatric deaths reported during a single season since reporting of influenza-associated pediatric deaths began (excluding the 2009–10 influenza A[H1N1]pmd09 pandemic) occurred during the 2024–25 season. 

Through September 13, 2025, a total of 280 influenza-associated pediatric deaths were reported, representing a national rate of 3.8 deaths per 1 million children. The median age at death was 7 years, and 56% of children who died had at least one underlying medical condition. Influenza A viruses were associated with 240 (86%) of the deaths. Forty percent of children who died were treated with influenza antiviral medications. Among the 208 pediatric decedents with available data who were eligible for influenza vaccine, 89% were not fully vaccinated. 
CDC recommends that all persons aged ≥6 months who do not have contraindications receive the influenza vaccine each year, ideally by the end of October.

       (Continue . . . ) 


Pediatric Influenza-Associated Encephalopathy and Acute Necrotizing Encephalopathy — United States, 2024–25 Influenza Season

Weekly / September 25, 2025 / 74(36);556–564
 
Amara Fazal, MD1; Elizabeth J. Harker, MPH1; Varsha Neelam, MPH1; Samantha M. Olson, MPH1; Melissa A. Rolfes, PhD1; Katie Reinhart, PhD1; Krista Kniss, MPH1; Aaron Frutos, PhD1,2; Jerome Leonard, MD1,2; Carrie Reed, DSc1; Vivien G. Dugan, PhD1; Haytham Safi, MD3; Theresa M. Dulski, MD3,4; Adrianna Stanley-Downs, MD5; Aaliya Bhatti, MPH5; Isaac Armistead, MD6; Suchitra Rao, MBBS7; Carola Torres-Diaz, MPH8; Ashlin Thomas, MPH8; Andy Weigel, MSW9; Michael Patten, DO9; Mallory Sinner, MPH10; Dawn Nims, MPH10; Crystal Mattingly, MPH10; Valerie Gosack, MLS11; Amy Voris12; Jaime Redkey, MS13; Felicia A. Scaggs Huang, MD14,15; Danielle DeCesaris, MPH14; Carrie Tuggle, MPH16; Kristina A. Betters, MD17; Julie Hand, MSPH18; Anna Krueger, MS19; Dina Z. Potter, MD19; Curi Kim, MSPH20; Rachel Park, MSc20; Sue Hong, MD21; Hannah E. Edelman, MD21; Sue Kim, MPH22; Justin Henderson, MPH22; Melissa McMahon, PhD23; Jeffrey Sanders, MPH23; David A. Hunstad, MD24; Emma L. Doran, MD25; Khalil Harbi, MSPH25; Derek Julian, MPH26; Hannah Ball, MPH26; John Dreisig, MPH27; Deepam Thomas, MPH28; Justin Faybusovich, MPH28; Yomei P. Shaw, PhD29; Nancy Eisenberg, MPH30; Richa Chaturvedi, MPH31; Ashleigh Faulstich, MPH31; Rachel E. Wester, MPH32; Donna L. Gowie32; Nicholas Fisher33; Melissa Sutton, MD34; Sameh W. Boktor, MD35; Jonah M. Long, MPH35; Patricia Marshall, MS36; Abby L. Berns, MPH36; Lindsey McAda, MPH37; Sarah Winders, MPH38; Pamela Gomez Pinedo, MPH39; Jade Murray, MPH39; Ta’Kindra Westbrook, MPH40; Anna Unutzer, MPH41; Scott Lindquist, MD41; Thomas E. Haupt, MS42; Kaylyn Baum, MPH43; Molly Wilson-Murphy, MD44,45; Carol Glaser, MD5,45; Kathleen Harriman, PhD5,45; James W. Antoon, MD, PhD17,45; Keith P. Van Haren, MD45,46; Adrienne G. Randolph, MD45,47; Andrew Silverman, MD45,46; Annabelle de St. Maurice, MD45,48; Sascha Ellington, PhD1; Timothy M. Uyeki, MD1,*; Shikha Garg, MD1,*; CDC Influenza-Associated Encephalopathy Collaborators (VIEW AUTHOR AFFILIATIONS)View suggested citation

Summary

What is already known about this topic?

Influenza-associated encephalopathy (IAE) is a rare, severe neurologic complication of influenza.

What is added by this report?

During the high-severity 2024–25 influenza season, 109 U.S. pediatric IAE cases were identified; 55% of affected children were previously healthy. Thirty-seven IAE cases were subcategorized as acute necrotizing encephalopathy (ANE), a severe form of IAE characterized by rapid neurologic decline and a poor prognosis. Overall, 74% of IAE patients were admitted to an intensive care unit, and 19% died; 41% of ANE patients died. Only 16% of vaccine-eligible IAE patients had received the 2024–25 influenza vaccine.

What are the implications for public health practice?

All children are at risk for severe neurologic complications of influenza. Annual influenza vaccination is recommended for all children aged ≥6 months to prevent influenza and associated complications, potentially including IAE.

Full Issue PDF

Abstract

In January 2025, CDC received several reports of deaths among children aged <18 years with a severe form of influenza-associated encephalopathy (IAE) termed acute necrotizing encephalopathy (ANE). Because no national surveillance for IAE currently exists, CDC requested notification of U.S. pediatric IAE cases from clinicians and health departments during the 2024–25 influenza season, a high-severity season with a record number of pediatric influenza-associated deaths.

Among 192 reports of suspected IAE submitted to CDC, 109 (57%) were categorized as IAE, 37 (34%) of which were subcategorized as ANE, and 72 (66%) as other IAE; 82 reports did not meet IAE criteria and were categorized as other influenza-associated neurologic disease.

The median age of children with IAE was 5 years and 55% were previously healthy, 74% were admitted to an intensive care unit, and 19% died; 41% of children with ANE died. Only 16% of children with IAE who were vaccination-eligible had received the 2024–25 influenza vaccine. Health care providers should consider IAE in children with encephalopathy or altered level of consciousness and a recent or current febrile illness when influenza viruses are circulating.
Annual influenza vaccination is recommended for all children aged ≥6 months to prevent influenza and associated complications, potentially including severe neurologic disease such as IAE and ANE.

        (Continue . . . ) 

While the current flu vaccine admittedly isn't a perfect solution, it can substantially reduce the burden of influenza.

In a related MMWR report on the effectiveness of the Southern Hemisphere's flu vaccine against hospitalization, the authors report: `During the 2025 Southern Hemisphere influenza season, seasonal influenza vaccination reduced influenza-associated outpatient visits by 50.4% and hospitalization by 49.7%.'

Along with pervasive anti-vaccine rhetoric on social media - we've also seen frequent demonization of antivirals - which have long been debunked (see Study Finds No Relationship Between Suicide & Oseltamivir In Pediatric Patients). 

To be most effective, antivirals need to be taken early (first 24-48 hrs), yet many parents (and some doctors) remain slow to opt for antiviral treatment. 

A recent study (see JAMA Neuro: Influenza With and Without Oseltamivir Treatment and Neuropsychiatric Events Among Children and Adolescents) shows clear benefit for early administration of oseltamivir, with the authors writing:
In this cohort study, oseltamivir treatment during influenza episodes was associated with a reduced risk of serious neuropsychiatric events. These findings support oseltamivir use for prevention of these influenza-related complications.

While a sharp increase in pediatric IAE/ANE cases has been reported in the U.S. over the past year, it isn't clear whether this represents a genuine increase or is due to improved detection and reporting following the CDC's call for increased surveillance and reporting last February.

To sort this out, we'll need vastly improved surveillance and reporting over multiple flu seasons, as explained in yesterday's MMWR.

No consensus standardized diagnostic or surveillance case definitions for IAE currently exist. Additional measures are needed to develop and implement surveillance to improve understanding of the incidence, potential risk factors, severity, and public health impact of IAE in the United States.

CDC is integrating surveillance for IAE and ANE into existing CDC-sponsored surveillance systems for the 2025–26 influenza season to better understand these serious and potentially preventable complications of influenza.

But until we know more, the seasonal flu shot and early access to antiviral medications, are our best options to lower the impact of flu on pediatric (and adult) populations. 

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Thursday, September 25, 2025

V. Research: Identification of H1N2 Influenza Viruses in Turkeys After Spillover from Swine and In Vitro Characterization

 

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Normally, our concern with the cross species transmission of flu viruses between birds and pigs is that an avian flu strain will jump to swine (see graphic above) and reassort into a more mammalian adapted virus. 

But today, we have a detailed report on the opposite.  A swine H1N2 virus jumping from pigs to turkeys (and infecting a human), in France.  

In 2020, a new swine H1avN2#E virus appeared in pigs in Brittany and rapidly become dominant (see ANSES Reports A `New' Swine Flu Virus Has Taken Over Other Genotypes in France). 

Around the same time, this swine virus was also reported in adjacent turkey farms. This excerpt from the aforementioned ANSES report:

In addition to the impact on the pig sector, the emergence of a new variant may also increase the risk of transmission to other animal species and to humans. “The H1avN2#E virus has caused several outbreaks of infection on turkey farms since 2020 and was responsible for a serious human case of swine flu in 2021.
Human exposure to swine influenza viruses increases the risk of reassortment with a human flu virus, which could lead to the emergence of a virus that is better adapted to humans. As pigs are also susceptible to human and avian influenza viruses, these animals can end up being mixing vessels for viruses. The last flu pandemic, which occurred in 2009, was caused by a swine influenza virus” underlines the scientist.

Just over 4 years ago, in Santé Publique France: Novel H1N2v Flu Infection In Côtes d'Armor, Brittany we looked at the first detection of what was then described as - an influenza A (H1N2) v clade 1C virus. 2.4 of porcine origin - in a man living near swine farms in Northwest France. 

Somewhat confusingly, while these swine/turkey and human swine variant viruses have different names, they are actually closely related (see graphic below).  Naming conventions are not standardized between public health and veterinary research. 

But for convenience sake, we'll stick to the H1avN2#E genomic designation in today's blog. 

While the human case, and the spillover into turkeys, has been previously reported, we've a follow up report today on the evolution, and apparent (turkey) farm-to-farm transmission of this emerging swine virus. 

Interestingly, the authors consider the possibility of short-or-medium distance airborne spread between farms (see Revisiting the Environmental Persistence and Airborne Spread of HPAI H5), along with other routes; including the transport of pigs in open vehicles, movement of contaminated trucks, equipment and personnel, and possibly swine slurry.
 
The authors identified 9 different spillovers into turkey farms, and the subsequent spread to 10 other farms. They also identified a number of potential turkey adaptation markers; HA: E233K or E236K and NA: T401N  and S416N.

While these viruses are obviously not ready for prime time - when you add the severe human infection from 2021- you have the basic ingredients for an emerging zoonotic threat. 

Due to its length, and detailed nature, I've only posted some excerpts. Those interested in a deep dive should follow the link to read it in its entirety. 

Identification of H1N2 influenza viruses in turkeys after spillover from swine and in vitro characterization

Chloé Chavoix a d, Pascale Massin a, François-Xavier Briand a, Katell Louboutin a, Rachel Busson a, Florent Souchaud a, Gautier Richard b, Claire Martenot a, Aurélie Le Roux b, Edouard Hirchaud b, Yannick Blanchard b, Sophie Le Bouquin-Leneveu c, Axelle Scoizec c, Céline Deblanc b, Séverine Hervé b, Audrey Schmitz a, Eric Niqueux a, Gaëlle Simon b, Ronan Le Goffic d, Béatrice Grasland a 
https://doi.org/10.1016/j.virusres.2025.199634 
Under a Creative Commons license
Open access

Highlights
  • Transmissions of a new H1N2 IAV from swine to turkey occurred in France.
  • This virus might have been transmitted between turkey farms.
  • E233K or E236K on HA, T401N and S416N on NA may be markers of adaptation in turkeys.
  • Viruses showed slight differences across mammalian-origin cell lines.
  • Eggs allowed more discrimination between viruses but were less efficient than cells.

Abstract

Influenza A viruses (IAVs) circulate among animals and humans and can cross species barriers to adapt to new hosts. In France, since 2020, a new genotype named H1avN2#E has predominated in pig farms. In parallel, this virus was detected in 19 breeding turkey flocks and in a human case, indicating interspecies transmission.
The objectives of this study were (i) to analyze viral sequences detected in turkeys between April 2020 and January 2023 and compare them with swine sequences to identify potential markers of adaptation and (ii) to characterize three representative viruses in vitro and in ovo on MDCK, MLE15 and A549 cells, as well as on embryonated chicken eggs.
Results suggest that following initial swine-to-turkey spillovers, the virus circulated between turkey farms. Phylogenetic analyses and host origin guided the selection of three viruses: a reference swine virus (A), a turkey strain closely related to swine viruses (B) and a virus apparently circulating in turkeys (C). Three molecular markers may contribute to turkey adaptation: the E233K, under positive selection pressure, or E236K mutations in the 220-loop of the receptor-binding site of HA protein and two NA substitutions, T401N in antigenic site 2d and S416N. 
Replication kinetics showed that at low MOI (0.001), virus C produced more infectious particles on MDCK and A549 cells, whereas at high MOI (0.1), virus B produced more. In ovo, infectious particles were generated for viruses A and B but not efficiently for virus C, in contrast to mammalian cells where production was higher.

        (SNIP)


        

In conclusion, this study demonstrated swine-to-turkey spillovers of the H1avN2#E virus, first identified in swine in 2020, and provided evidence of possible turkey-to-turkey transmission.
A glutamate-to-lysine substitution at positions 233 or 236 of the HA RBS 220-loop may represent an adaptation marker for turkeys. Similarly, NA substitutions T401N in antigenic site 2d and S416N may represent a feature associated with turkeys, despite the absence of detectable positive selection.
Viral and genomic replication kinetics revealed subtle differences among the three viruses, with the “Turkey virus” producing higher titers in MDCK and A549 cells at MOI 0.001 while the “Turkey-swine-like virus” yielded more at MOI 0.1. In embryonated chicken eggs, infectious particles were produced for the “Turkey-swine-like virus” and “Swine virus” but not efficiently for the “Turkey virus”.
Further characterization of these H1N2 viruses in additional host-derived cells and in vivo models would be needed to better capture the complexity of host-virus interactions.

        (Continue . . . )
 

For more on the growing zoonotic threat from European swine flu viruses, you may wish to revisit last April's:


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