Saturday, March 07, 2026

California DPH Advice to Public After H5N1 Detected in Elephant Seals

Credit Wikipedia

#19,077 

Ten days ago in  California: Background on the Outbreak of H5N1 in Elephant Seals at Año Nuevo Natural Reserve, we looked at the first reports of the detection of HPAI H5 in North American Elephant Seals.  

We also reviewed the devastating outbreaks previously reported in South America, and looked back at several studies on its increasing transmission among marine mammals (see here, here, and here). 

The initial report announced that 7 weaned seal pups had tested positive, after a small number of seals (later described by media as ~ 30) showed signs of illness (abnormal respirations, tremors, and neurological symptoms).

Disappointingly, we still don't have any publically released information on the genotype - or any other genomic information - beyond the subtype (reportedly H5N1).

According to their own documentation, a national reference lab like the NSVL should  be able - assuming they received viable, high quality samples - to sequence a priority novel flu virus in less than a week.

But in actual practice (see Nature: Lengthy Delays in H5N1 Genome Submissions to GISAID), the public release of data often takes weeks or even months. 

Official updates have been noticeably scant since the original announcement, but last night the California Department of Public Health published their first communications on this event, where they urge the public to be extra cautious around marine mammals and wild birds. 

​March 6, 2026
NR26-010

Bird flu detected in elephant seal pups at Año Nuevo State Park; risk to public remains very low 

but officials urge caution 

What You Need to Know: H5N1 bird flu has been confirmed for the first time in northern elephant seal pups at Año Nuevo State Park​ in San Mateo County. While the risk to the general public remains very low and there is no evidence of seal‑to‑human transmission, CDPH urges people to avoid contact with sick or dead wildlife, including dead birds, to limit the potential transmission of bird flu to humans. Local, state, federal and academic partners continue to monitor and test wildlife to understand the scope of the incident. 

SACRAMENTO – The California Department of Public Health (CDPH) is urging the public to avoid contact with dead or distressed marine mammals and wild birds along the California coast after H5N1 bird flu, also known as highly pathogenic avian influenza (HPAI), was confirmed in weaned northern elephant seal pups at Año Nuevo State Park in San Mateo County. Wildlife workers are closely monitoring nearby beaches in San Mateo and Santa Cruz counties and conducting additional surveillance from Sonoma to San Luis Obispo County to better understand the possible spread of this disease.  ​

These findings represent the first documented cases of bird flu in northern elephant seals and the first detection of the virus in any marine mammal in California. As a precaution, California State Parks has closed key areas and cancelled public tours at Año Nuevo State Park for the remainder of the season to protect the animals and minimize the potential spread of disease.

“While the detection of bird flu in these young seals is concerning, it also shows that our surveillance systems are functioning as intended,” said Dr. Erica Pan, CDPH Director and State Public Health Officer. “The risk to the general public remains very low, but Californians can protect themselves and their pets by avoiding contact with sick or dead marine mammals or birds, keeping pets on a leash near beaches, and respecting area closures. CDPH will continue to work closely with local, state, federal and academic partners to monitor this situation, support safety for workers who may be exposed, and provide updates as more information becomes available.” 

What Californians Can Do: Avoid Contact with Wildlife 
Bird flu is a disease that has the potential to spread between animals and people, including pets. Although the risk of infection to the general public remains very low and there is no evidence of seal-to-human transmission, beachgoers should not touch live or dead marine mammals or birds or allow pets to approach these wild animals.  

CDPH guidance for the public: 

  • Stay 150 yards away from elephant seals and all wild marine mammals and seabirds whenever possible. 

  • Keep children and pets away from sick, injured or dead wildlife. 

  • Do not approach, touch or attempt to assist marine mammals or seabirds, as this can spread disease and cause harm to both animals and people. 

  • Transporting potentially sick wildlife to a rehabilitation center, veterinary clinic or other animal facility can increase exposure risk. Always contact the facility first​ for guidance and to determine if the animal should be collected. 

  • Report sightings of sick, injured or dead marine mammals to the NOAA West Coast Marine Mammal Stranding Hotline: (866) 767‑6114. 

  • Report sick or dead birds to the California Department of Fish and Wildlife


CDPH recommendations for wildlife workers:  

  • Wear appropriate personal protective equipment (PPE) including gloves, eye protection and respiratory protection when working with sick or dead marine mammals.  

  • Report any influenza-like symptoms after exposure to your local health department.  

  • Seek testing if any symptoms develop within 10 days post-exposure. Persons with influenza (either regular seasonal influenza or bird flu) may be eligible for antiviral treatment to reduce disease severity.   

  • If you’re not feeling well after a possible exposure: 

  • Stay home, rest, and avoid contact with others except to get medical care. If you seek care for symptoms, notify your healthcare provider of your potential exposure to bird flu before or immediately on arrival. 

  • Wear a mask indoors around other people and when entering any healthcare facility. 

  • Wash your hands often (or use hand sanitizer with at least 60% alcohol if soap and water aren’t available). ​

Bird flu infections in people are rare, but infection can occur if the virus enters a person’s eyes, nose or mouth, or is inhaled during close unprotected contact with infected animals or by touching contaminated surfaces and then touching the eyes, nose or mouth. Pets such as dogs and cats may also be at risk of illness if they interact with infected wildlife. 

What CDPH is Doing: ​
CDPH is actively coordinating with California State Parks, the California Department of Fish and Wildlife, NOAA Fisheries, UC Davis, UC Santa Cruz, The Marine Mammal Center and the US Department of Agriculture to monitor and respond to incidents involving sick and dead elephant seals and other marine mammals. 

CDPH is supporting and advising local health departments with monitoring exposed personnel, providing appropriate personal protective equipment (PPE) and testing when needed, and ensuring public health and wildlife safety. Surveillance of wildlife in coastal areas has increased, and CDPH continues to monitor statewide influenza activity for any signs of bird flu in humans. 
Incident Timeline 
Initial signs of illness were observed in seal pups on February 19–20, when researchers noted weakness, tremors, seizures, abnormal neurological behavior and sudden death in some animals. Samples collected from sick and deceased pups tested positive for influenza A and were subsequently confirmed as H5N1 by the USDA National Veterinary Services Laboratories. 

With the spring northbound migration of birds now firmly underway, we've seen Several States Warn On Contact With Wild Birds/Mammals in recent weeks.  


While the public remains largely apathetic to the threat of HPAI (see Two Surveys (UK & U.S.) Illustrating The Public's Lack of Concern Over Avian Flu), the reality is the risks - while still fairly low - continue to increase. 

Making the above advice very much worth heeding. 

Friday, March 06, 2026

IJID: Lack of Respiratory Droplet Transmission of Two Recent Human Influenza A(H5N1) Viruses in Female Ferrets

 

#19,076

Today we've a study that reminds us how much we've yet to learn about what it takes for a novel zoonotic virus - like HPAI H5Nx - to turn into a genuine pandemic threat.  

First, a bit of history.

In the months following the discovery of first human infection with the Bovine B3.13 H5N1 virus (aka TX/37) in March of 2024, we saw a number of conflicting reports on the virulence and transmissibility of the HPAI virus in ferrets (see CDC: Updated Results On Texas H5N1 Virus In Ferrets).

Differences in methodology, equipment used, and endpoints, the host source (human vs bovine), viral evolution during isolation (cell culture vs eggs), and the use of a relatively small number of test animals all could have contributed to these mixed results.  

A reminder that no study design is perfect, that research is often incremental, and that we should view each new finding in the context of what has previously been reported by others.   

I mention all of these limitations because today's study, once again, provides some unexpected results. 

Researchers at the Kawaoka lab at the University of Wisconsin-Madison, along with international partners took two human isolates (1) B3.13 from a Dairy Worker in Michigan (MI90) and (2) a D1.1 from the B.C. adolescent (BC2032) who was critically ill, and tested their transmissibility in female ferrets. 

  • Interestingly, the B3.13 virus (MI90) - which only caused mild conjunctivitis in its human host - caused severe disease, extra-respiratory spread, and was lethal in test ferrets.
  • While the D1.1 virus (BC2032) - which put a teenage girl on ECMO - produced milder illness and no lethality in ferrets. 
  • And neither virus transmitted via respiratory droplets in ferrets.

In addition to these non-intuitive findings, the authors also report that previous studies found the D1.1 (BC2032) strain led to 100% lethality in ferrets, while earlier studies found the MI90 strain caused `. . . sub-lethal disease in ferrets, with respiratory droplet transmission detected in 50% of naïve exposed animals.'

As we've discussed often, we have only a partial understanding of what genetic changes are needed to increase the virulence, transmissibility, or host range of a novel influenza A virus like HPAI H5. 

Scientists often look for a handful of known amino acid changes (e.g. PB2 mutations like E627K, D701N, Q591K, and M631L and HA mutations like Q226L and E190D) which may favor mammalian adaptation, but new ones (see Sci. Adv.: PB2 and NP of North American H5N1 Virus Drive Immune Cell Replication and Systemic Infections) continue to be discovered.

And many minor, seemingly innocuous genetic changes - when stacked in the right combination - can greatly increase or decrease, their impact. 

Exactly what part these (and other) factors may have played in today's unexpected results remains to be seen. I've just posted the abstract, and some brief excerpts, so follow the link to read the study in its entirety. 

I'll have a brief postscript after the break.

Lack of Respiratory Droplet Transmission of Two Recent Human Influenza A(H5N1) Viruses in Female Ferrets
Tong Wang 1, Chunyang Gu 1, Lizheng Guan 1, Asim Biswas 1, Tadashi Maemura 1, Hassanein H. Abozeid 1 2, Peter J. Halfmann 1, Gabriele Neumann 1, Amie J. Eisfeld 1, Yoshihiro Kawaoka 1 3 4 5 
https://doi.org/10.1016/j.ijid.2026.108514 Get rights and content
Under a Creative Commons license
 
Highlights
  • Two human clade 2.3.4.4b H5N1 viruses (B3.13 and D1.1) were tested in ferrets.
  • MI90-H5N1 (B3.13) caused severe disease, extra-respiratory spread, and lethality.
  • BC2032-H5N1 (D1.1) caused milder disease with no lethality in ferrets.
  • Neither virus transmitted via respiratory droplets in ferrets.
  • Respiratory droplet transmissibility of clade 2.3.4.4b H5N1 viruses appears variable.
Abstract

Background
Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) (HPAI H5N1) viruses are widespread globally and have transmitted from birds to dairy cattle at least four times in the United States, including once by a genotype B3.13 virus and three times by genotype D1.1 viruses. Despite their prevalence and known ability to infect humans, only a few studies have examined respiratory droplet transmission capabilities of clade 2.3.4.4b viruses in mammalian models of influenza infection.
Methods

Here, we assessed respiratory droplet transmission of two recent human clade 2.3.4.4b HPAI H5N1 viruses – A/Michigan/90/2024 (‘MI90-H5N1’), a B3.13 isolate, and plaque-purified A/British Columbia/PHL2032/2024 (‘BC2032-H5N1’), a D1.1 isolate – in the ferret model.

Findings

We found that MI90-H5N1, in contrast to earlier findings, causes severe disease and partial lethality in ferrets, with virus spread to extra-respiratory organs and no respiratory droplet transmission. BC2032-H5N1 caused less severe disease with no lethality in ferrets and, consistent with a recent report, failed to transmit via respiratory droplets.

Interpretation

Together with other reports, our results suggest that respiratory droplet transmissibility of clade 2.3.4.4b viruses is variable. Therefore, continued monitoring and risk assessment for emerging HPAI H5N1 viruses is essential to better understand their pandemic potential.
(SNIP)

A limitation of this study is that transmission was assessed in a single mammalian model under defined laboratory conditions, which may not fully capture variability in natural exposures or host species. 

Only single isolates of each genotype were evaluated,and the BC2032-H5N1 virus used here was plaque-purified, capturing only one variant from a clinically heterogeneous sample.

Additionally, female ferrets were used in our  experiments, whereas the CDC study employed male ferrets; potential effects of sex on disease severity or transmission efficiency were not assessed. 

Finally, modest sample sizes could limit detection of rare transmission events.

Overall, these findings underscore that while some clade 2.3.4.4b H5N1 viruses can transmit via respiratory droplets, transmission efficiency is variable and may be dependent on virus genotype, pathogenicity, and other host and/or environmental factors. Therefore, it is critical to continue monitoring and risk assessment for emerging HPAI H5N1 viruses to better understand their pandemic potential. 

 

Obviously, there is still a great deal of uncertainty in influenza research. This isn't the first time we've confronted conflicting data, nor will it be the last.  A few past blogs include:

When Studies Collide (COVID-19 Edition)

When Flu Vaccine Studies Collide

When Studies Collide (Revisited)

Why Preprints Are Only Preprints

A reminder that gaining scientific knowledge is a process . . . one that evolves over time and often involves detours, setbacks, and constant reevaluation. 

Assuming scientific certainty about anything is often the first step towards a humbling. 

But even with its limitations, it is still the best method we have to understand our surroundings. 

Thursday, March 05, 2026

UK Defra Announces New Avian Influenza Vaccine Trials Begin in UK

 

#19,075

With agricultural losses mounting from avian influenza, more and more farmers are clamoring for the ability to protect their flocks with vaccines, yet many countries remain slow to embrace that strategy.

While poultry vaccination would seem to be the ideal solution, its success rate over the years has been inconsistent, and we've seen evidence that suboptimal formulations and application can help drive viral evolution

Although we've seen some impressive success stories (see OFID: Avian H5, H7 & H9 Contamination Before & After China's Massive Poultry Vaccination Campaign), we've also seen some significant failures (see J. Virus Erad.: Ineffective Control Of LPAI H9N2 By Inactivated Poultry Vaccines - China), often due to poorly designed and/or applied vaccines.
The problem is that a vaccine that is only partially effective may merely mask the symptoms of infection, but still allow the virus to spread stealthily and continue to evolve (producing vaccine-induced escape mutants).

Eleven months ago, in NPJ Vaccines: Impact of Inactivated Vaccine on Transmission and Evolution of H9N2 Avian Influenza Virus in Chickensa report warned that inactivated vaccines have failed to prevent - or even reduce - H9N2 in China's poultry, and may have driven viral evolution (including mammalian adaptations).

In 2023 WOAH (formerly the OIE) announced a policy shift (see WOAH: Rethinking Avian Influenza Prevention and Control Efforts) that recommended a comprehensive control strategy that integrates vaccination with other measures (including testing & culling if needed).

But most countries - including the United States, Canada and the UK - have yet to authorize HPAI poultry vaccines, although many are studying the matter.

This statement from Canada's CFIA:
Why Canada doesn’t currently vaccinate poultry against HPAI

Canada has historically maintained an HPAI response strategy focused on disease eradication and does not currently vaccinate poultry to protect against HPAI. The scale and duration of the ongoing outbreak, however, has increased global interest in exploring vaccination as a tool for disease management. Some countries already use vaccines as a preventative measure.
Last March's UK Joint Taskforce Policy Paper: Vaccination of Birds Against HPAIV (bird flu) continues to promote eradication, warning:
Use of avian influenza vaccine may reduce poultry mortality and clinical signs of the disease following infection. However, vaccinated birds can still become infected, shed virus, and transmit the virus to other vaccinated or unvaccinated birds, mammals and humans.
Last July the UK published an independent report outlining the many challenges inherent in adopting a vaccination strategy, which discussed the possibility of conducting a limited and targeted turkey vaccination trial as a first step.

Today the Defra announced that a six-month trial has begun (see below), on a small group of birds under strict supervision. 

First the press release, after which I'll have a postscript.

Press release

New avian influenza vaccine trials begin in UK

New targeted trial in turkeys will test vaccine efficacy as part of fight to protect wild and captive birds

From:Department for Environment, Food & Rural Affairs, Animal and Plant Health Agency and Baroness Hayman of Ullock Published 5 March 2026

Highly pathogenic avian influenza (HPAI) vaccine trials have started today (Thursday 5 March) in a major step forward in the fight against the disease.

New trials will explore the potential for the latest vaccines to protect birds, focusing on turkeys only in England, providing valuable insight into how well vaccines work in the field, how surveillance can be managed to retain trade and how vaccines can help manage the disease.

The scale of avian influenza outbreaks in the UK and Europe within the last few years has been unprecedented, causing devastation for bird keepers on the frontline and the poultry sector. Annual outbreaks cost the UK Government and industry up to £174m each year. The disease has significantly impacted both captive and wild birds globally since 2020.

Turkeys have been selected as a priority species for further research as they are highly susceptible to avian influenza, with outbreaks resulting in severe clinical signs with rapid and elevated mortality rates.

The trial will sample a small group of birds under strict supervision following approval from the Veterinary Medicines Directorate (VMD) and using UK/ EU authorised vaccines. Vaccinating poultry against bird flu is not currently allowed more widely in the UK.

 Biosecurity Minister Baroness Hayman said:

We know what a terrible toll this disease has annually on our farmers and poultry sector.

The start of new vaccine trials are a significant step forward in our fight against this disease and will contribute to global research efforts. We are hopeful vaccines can be used in the UK as an additional tool to control bird flu to protect the UK’s biosecurity and food supply.
UK Chief Veterinary Officer Christine Middlemiss said:
This targeted trial is going to be really key for our understanding of how HPAI vaccines can be effectively used for disease control in the UK. They have the potential to be a really valuable additional tool in helping us protect birds from infection.

Stringent biosecurity will always remain our best defence and I urge all bird keepers to continue to take the steps needed to prevent avian influenza spreading onto their premises.
Animal and Plant Health Agency Avian Influenza Disease expert Professor Ashley Banyard said:
The scourge of this disease has impacted both captive and wild birds populations globally since 2020. The impact has varied annually, which makes forecasting of disease events very difficult.

Assessing the ability of these vaccines to generate an immune response in turkeys will give a good indication of the suitability of these vaccines as tools to protect birds against H5N1.
The trial will evaluate how vaccines could be safely and effectively integrated into the UK’s disease control strategy, generate data on vaccine efficacy and contribute to the growing international body of research on HPAI vaccination. It will help us understand how vaccines can be effectively used in the UK as an additional tool to control bird flu and provide valuable information on vaccine effectiveness and contribute to global research efforts, during these challenging times,

The potential benefits of HPAI vaccination are being considered in several countries experiencing similar challenges to the UK. In Europe there are ongoing trials of vaccines in Italy and the Netherlands.

Stringent biosecurity remains the best defence against the disease. All bird keepers should familiarise themselves with the steps they need to take to prevent bird flu and avoid any potential for it to spread. Remaining vigilant for signs of disease, and reporting this promptly, will help to keep birds safe.

The trials will last for 24 weeks and will provide insight into the final recommendations of the UK HPAI vaccination taskforce.

ENDS

Notes to editors: In July 2025, the Taskforce published a report outlining the current status and challenges of vaccination, exploring future options for vaccination of birds in different sectors including a cost benefit analysis and a recommendation for a domestic field vaccination trial in turkeys.

With poultry vaccination programs, the devil is always in the details.  

Last August, in Vaccine X: H5N1 Highly Pathogenic Avian Influenza Vaccination: Seroresponse of Mexican Poultry in the 2022–2024, we looked at the first two rounds of HPAI poultry vaccination in Mexico. 

While seroconversion and seroprotection rates approached or exceeded 80% in many states, looking at the breakdown of the 20 states included in the first round, 7 (33%) scored considerably lower, with 2 states in single digits. 

The authors noted:

These limitations were evident in period one, mainly across southeastern Mexican states because they did not mount an immune response after vaccination with seroconversion and seroprotection rates less than 10 % of their population.

It is likely that some of the critical points of the vaccination plan were not fully met or were not carried out properly.

And that's the rub.  What may work perfectly under strict supervision can fall apart in the real world due to poor or careless execution. And when that happens, it can afford the virus new opportunities to spread or evolve. 

Surveillance and frequent testing of vaccinated flocks is also crucial in order to detect `silent' infections.  This can't be a `vaccinate and forget' strategy. 

Although poultry vaccination may well be our best (or only) control option going forward, it is imperative that it is done consistently, properly, and with continually updated vaccines. 

Else we risk making a bad problem considerably worse. 

Wednesday, March 04, 2026

OFFLU: Global Overview of Spread & Impact of H5 Clade 2.3.4.4b HPAI virus in Wildlife, 2020-2024

#19,074

Offlu has just published a 77-page overview on the impact of the  HPAI H5Nx virus on global wildlife during the opening years (2020-2024) of this ongoing, and unprecedented, epizootic.  

As you can see by the table of contents (below), there is far too much to adequately detail in this blog.  


While the data largely tells us where we've been, this document also  makes recommendations on where we need to be going, if we hope to limit the damage from this virus. 

Download it both as a reference, and as a guide going forward. 


Vaccines: Investigation of Potential Cross-Protection Conferred by the Seasonal Influenza Vaccine Against Swine Influenza A Viruses of Pandemic Potential

 

#19,073

Last week Spain reported a rare human infection with H1N1v swine influenza in a patient in Catalonia with no known history of exposure to pigs, or to a contaminated environment. 

While reports like this are not common, it is assumed that these cases are largely underreported, since symptoms are likely to be mild-to-moderate, and most people don't get tested for uncomplicated flu.

We've seen estimates that perhaps 1 in 100 swine variant cases here in the United States are actually picked up by surveillance (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012).

Results. We estimate that the median multiplier for children was 200 (90% range, 115–369) and for adults was 255 (90% range, 152–479) and that 2055 (90% range, 1187–3800) illnesses from H3N2v virus infections may have occurred from August 2011 to April 2012, suggesting that the new virus was more widespread than previously thought. 

The CDC's IRAT (Influenza Risk Assessment Tool) lists 3 North American swine viruses as having at least some pandemic potential (2 added in 2019).
H1N2 variant [A/California/62/2018] Jul 2019  5.8 5.7 Moderate
H3N2 variant [A/Ohio/13/2017]         Jul 2019  6.6 5.8 Moderate
H3N2 variant [A/Indiana/08/2011]     Dec 2012 6.0 4.5 Moderate

But there is much diversity among swine flu viruses around the globe, with China's EA H1N1 `G4' virus often cited as the biggest pandemic threat. We've also followed repeated spillovers in Brazil, and last year the Eurasian 1C Swine Influenza A Virus was labeled a `high pandemic risk'.

The reality is, surveillance and testing for swine influenza A viruses is notoriously sub-optimal, and many strains circulate under the radar. 

While swine influenza A viruses share the same HA and NA types as seasonal influenza (H1N1v, H1N2v, H3N2v, H3N1v, etc.) they are often antigenically distinct, making the value of deploying existing seasonal flu vaccines in the opening months of a swine flu pandemic unknown. 

In today's study, researchers from the Francis Crick Institute in London, and Italy's WOAH Reference Laboratory for Swine in Influenza tested 5 European lineages of swine influenza (see table below) against components of recent seasonal flu vaccines.

What they found was seasonal flu boosters offered moderate protection against some European swine flu strains (notably, 1C.2.1), but little or no protection against others, like 1A.3.3.2. 

I've reproduced the abstract, and some excerpts, from the study.  Follow the link to read it in its entirety.  I'll have a brief postscript after the break.

Investigation of Potential Cross-Protection Conferred by the Seasonal Influenza Vaccine Against Swine Influenza A Viruses of Pandemic Potential
Alice Lilley1,*, Chiara Chiapponi2, Alice Prosperi2, Ana Moreno2, Laura Soliani2, Nicola Lewis1 and Ruth Harvey1
Vaccines2026, 14(3), 211;https://doi.org/10.3390/vaccines14030211

Academic Editor
Published:25 February 2026

Abstract

Background/Objectives: Influenza A viruses cause seasonal epidemics of respiratory infections in humans, the severity of which can be mitigated by influenza vaccine use. Influenza A viruses circulating in pigs continue to pose a pandemic threat, as evidenced by the influenza virus that caused the 2009 pandemic, which originated in pigs. To understand the relative risk of emergence of influenza A viruses from pigs and to assess the potential role of the seasonal influenza vaccine in mitigating this risk, we evaluate the potential cross-protection afforded by the seasonal influenza vaccine against different clades of recently circulating swine influenza A viruses.
Methods: The presence of cross-reactive antibodies in pre- and post-vaccination human serum samples was measured in haemagglutination and microneutralisation assays. Representative H1 swine influenza A viruses from different genetic lineages were tested against sera collected after administration of the seasonal influenza vaccine in healthy adult volunteers over a 6-year time-period.
Results: Although a clade-dependent boosting of post-vaccination antibody titres was observed, protective titres often failed to be reached. There was heterogeneity in recognition by sera for the contemporary swine influenza A viruses, with the 1C.2.1 clade virus being well recognised in both assays, whilst very low pre- and post-vaccination antibody titres were observed against the 1A.3.3.2 clade (which emerged in pigs following the reverse zoonotic introduction from humans of the A/H1N1 pdm09 virus) by both assays.
Conclusions: Seasonal influenza vaccines produce cross-reactive antibodies against some clades of influenza A viruses circulating in pigs, but not all. Depending on the lineage and clade of the virus, the seasonal influenza vaccine might have utility in the event of a swine variant outbreak in humans, whilst a specific vaccine against the outbreak strain is developed.
       (SNIP)
A systematic review found that post-influenza vaccination antibody levels waned within six months but remained higher than pre-vaccination titres [31]. The administration of a booster dose of vaccine in the event of a swine influenza outbreak in humans is likely to help boost antibody titres in those who have previously been vaccinated, except for the 1A.3.3.2 virus.
However, only two time points (almost one year apart) are represented here, and therefore, conclusions about antibody titres at other time points cannot be made. Additionally, volunteers did not report influenza infections occurring during this time period, which could reduce the appearance of waning immunity in the cohort.

These results suggest that the seasonal vaccine does not induce cross-reactive antibodies against all lineages, or even all clades within a lineage, of swine H1 influenza A viruses.
The value of the seasonal vaccine in the event of a swine influenza outbreak will be dependent on the strain of virus, as will the benefit of administering a booster dose to those who have already been vaccinated. However, due to the availability of the seasonal vaccine, its use should be considered in response to a swine influenza outbreak while a strain-specific vaccine is produced.
Continued surveillance of SwIAV and development of candidate vaccine viruses is vital due to low population immunity in humans. Moreover, these results highlight the need for the continued promotion of influenza vaccination due to its ability to induce cross-reactive antibodies against some H1 swine influenza viruses.

       (Continue . . . )

 
While not a home run, there is enough evidence here to consider seasonal flu boosters in the opening months of a swine flu pandemic, at least against some European lineages. 

Whether the same benefits might be expected against other strains - from North America, Asia, or South America - isn't clear.  

But as the authors point out, this is yet another reason to get the seasonal flu vaccine each year, as it might provide some degree of baseline immunity against a swine flu pandemic. 

And any amount of protection in a pandemic beats none at all. 

Tuesday, March 03, 2026

J.I.D.: Development & Characterization of Candidate Vaccine Viruses against HPAI A(H5) Viruses for Rapid Pandemic Response

 
WHO H5 CVV list (n=46)

#19,072

Two days ago, in WHO: Candidate Vaccine Viruses for Pandemic Preparedness - Feb 2026, we looked at the latest WHO recommendations for CVVs (Candidate Vaccine Viruses) against zoonotic influenza viruses.

While no new H5 CVVs were recommended,  antigenic characterization of several recent isolates were pending, and H5 continues to evolve. 

Less well known is that the CDC also maintains their own list of  HPAI H5 CVVs - and while there are some overlaps with the WHO's list - there are some differences (see How The WHO & CDC Are Developing Candidate H5N1 Vaccines).   

On the same day that the WHO released their semi-annual zoonotic vaccine update recommendations, the Journal of Infectious Diseases published the following CDC review of 25 existing H5 CVVs, and how well they might work against current (U.S & Cambodian) H5N1 strains. 

CVVs are `seed viruses' which have been antigenically matched to various legacy strains of H5 - and were determined to grow reasonably well in an egg medium - which means they could be quickly used to begin vaccine manufacturing. 

The big caveat is that antigenic matching is done using HI assays in ferrets, which may not fully predict its effectiveness in humans. And - as this report cautions - even tiny changes in the virus can have major impact on its antigenic profile. 

In one of their studies, researchers looked at two clade 2.3.2.1e viruses collected from humans in Cambodia in 2023. The two isolates were:

  • A/Cambodia/NPH230032/2023
  • A/Cambodia/NPH230776/2023
Despite their genetic similarity, they reacted quite differently.  

  • Encouragingly, the A/Cambodia/NPH230032/2023 virus showed broad cross-reactivity against several legacy CVVs. 
  • A/Cambodia/NPH230776/2023, however, showed reduced cross-reactivity against many of those same CVVs, with only a specific 2.3.2.1 lineage CVV showing strong inhibition.
While it is possible that an interim vaccine might be developed early in the next pandemic based on an existing CVV - potentially shaving weeks or even months off the manufacturing process - a lot of things would have to go `right'
But since a targeted strain-specific vaccine could take 6 months or more to develop, having an existing library of CVVs to draw from might  save a lot of lives. 

I've only posted the abstract, and a few excerpts from the results and discussion. Follow the link to read it in its entirety. 
Development and Characterization of Candidate Vaccine Viruses against High Pathogenicity Avian Influenza A(H5) Viruses for Rapid Pandemic Response  
Li Wang , Jieru Wang , Jaber Hossain , Hans C Cooper , Cindy Adolphus , Michael Currier , Ginger Atteberry , Chenchen Feng , Marie K Kirby , Han Di ... Show more

The Journal of Infectious Diseases, jiag132, https://doi.org/10.1093/infdis/jiag132
Published: 28 February 2026
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Abstract

High pathogenicity avian influenza A(H5) viruses pose a pandemic threat. These viruses have rapidly evolved in birds and frequently crossed species barriers, resulting in over 1,000 confirmed human infections, with a case fatality proportion of approximately 50%. In response, the U.S. CDC has developed dozens of A(H5) candidate vaccine viruses (CVVs) over the past two decades, primarily targeting clades known to infect humans. This report summarizes the development and characterization of the CVVs, with a particular focus on their antigenic relationships with clades 2.3.2.1e and 2.3.4.4b A(H5N1) viruses, which have been responsible for the majority of recent human infections.
 
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Given the ongoing A(H5N1) outbreaks in birds and mammals, along with zoonotic transmission to humans caused by clades 2.3.4.4b and 2.3.2.1e, we aimed to evaluate the ability of antibodies raised against these CVVs in ferrets to inhibit hemagglutination of representative strains from these two clades. 

Three recent human A(H5) isolates were tested in the HI assay: A/Texas/37/2024(TX37), a clade 2.3.4.4b virus representing the first human case of the 2024 U.S. dairy cattle A(H5)outbreak; A/Cambodia/NPH230776/2023 and A/Cambodia/NPH230032/2023, both clade2.3.2.1e viruses isolated in 2023.

Seven out of 16 heterologous ferret antisera inhibited the TX37 virus with HI titers within a 2-fold difference compared to the homologous HI titer (Table 2). Out of those seven antisera, four were raised against CVVs belonging to genetic clades different from TX37.

Similarly, eight ferret antisera raised against these A(H5) CVVs inhibited A/Cambodia/NPH230032/2023 (2.3.2.1e) despite seven of the CVVs being from heterologous genetic clades. Interestingly, only two ferret antisera inhibited A/Cambodia/NPH230776/2023, though it belongs to clade 2.3.2.1e, the same clade as A/Cambodia/NPH230032/2023 (Table 2).

Twelve amino acid differences within HA1, including substitutions in the receptor-binding domain and antigenic site B, are likely responsible for the observed difference in cross-reactivity of CVV antisera against these two viruses (Supplementary Table 3).

DISCUSSION
In this study, we provided a comprehensive overview of 25 A(H5) CVVs developed at the CDC over the past two decades, including detailed information on their HA titers, EID₅₀ values, and viral protein yields. These CVVs have been distributed to government agencies, vaccine manufacturers, academic institutions, and other stakeholders to facilitate laboratory characterization, regulatory evaluation, and vaccine manufacturing. 

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While ferret antisera provide a valuable surrogate model for antigenic characterization, it is important to acknowledge their limitations. Species-specific differences in immune responses between ferrets and humans are well-documented for seasonal influenza viruses [13]. Human serological data for clades 2.3.2.1e and 2.3.4.4b viruses remain limited, although a recent study has begun to address this gap [14]. Future efforts should prioritize evaluating antibody responses in individuals vaccinated with A(H5) vaccines or previously infected with A(H5) viruses to better assess the potential for cross-protection against emerging zoonotic strains.

In conclusion, maintaining a diverse and regularly updated A(H5) CVV library is critical for global readiness as avian influenza viruses continue to evolve. The demonstrated cross-reactivity of several heterologous CVVs with current zoonotic strains underscores the importance of antigenic breadth in CVV selection and suggests that some stockpiled or previously developed candidates may provide adequate protection and enable rapid vaccine production, offering valuable lead time during outbreak response.