CMAJ: Avian Influenza and Use of the H5N1 Vaccine to Prevent Zoonotic Infection in Canada

 

#18,742

Last February the Canada's PHAC Announced Plans To Purchase 500,000 doses Of H5N1 Vaccine, joining the ranks of the United States (4.8 million doses), the UK (5 million doses), Japan (10 million doses), and the EU (initially 664,000 doses  but recently increased to 27+ million doses) who have all committed to major H5 vaccine purchases over the past 12 months. 

With the exception of a special release of 20,000 doses of H5N1 vaccine to Finland following their fur-farm epizootic (see Finland: MOH Announcement On Avian Flu Vaccine Availability For People At High Risk), these vaccines reportedly remained locked away, as nations debate under what circumstances, and who would receive them. 

In August of last year, Finland began a voluntary vaccination program (see THL Announces the Start Of H5 Vaccination For High Risk Groups) in hopes of preventing any potential H5N1/Seasonal flu co-infections which might lead to a reassortment event.

Finland was forced to quickly deploy their 20,000 doses of vaccine last year because it was near its expiration date. In the past we've seen stockpiled - and about to expire - H5N1 vaccines provided to high risk individuals in a similar `use it or lose it' strategy.

Hong Kong: H5N1 Vaccine Recommended For Certain Lab Workers

Japan Begins Pre-Pandemic Inoculation Of Health Care Workers

 Taiwan Offers Public Bird Flu Vaccinations

Last February, Canada's National Advisory Committee on Immunization (NACI) released a detailed (38-page)  set of preliminary guidance on the potential use of the H5N1 vaccine that considers when - and to whom -  it might be appropriate to deploy an H5N1 vaccine during a pre-pandemic time period.  

Today we have a commentary, published by the CMAJ (Canadian Medical Association Journal) which contemplates how, and when, local authorities might decide to utilize their recently ordered pre-pandemic stockpile of H5N1 vaccine.

This is obviously a discussion that is ongoing - albeit not always as publicly - in other countries as well. 

I've only posted some extended excerpts, so follow the link to read the commentary in its entirety, including references. 

Avian influenza and use of the H5N1 vaccine to prevent zoonotic infection in Canada
Alexandra Nunn, Angela Sinilaite, Bryna Warshawsky, Marina I. Salvadori, Isaac I. Bogoch and Winnie Siu
CMAJ June 02, 2025 197 (21) E599-E600; DOI: https://doi.org/10.1503/cmaj.250641

PDF

Key points

• Outbreaks of avian influenza A(H5N1) clade 2.3.4.4b viruses continue to be widespread among birds and poultry in many parts of the world, with transmission to mammals including humans in some countries and dairy cattle in the United States.

• These viruses are considered to have pandemic potential owing to their ability to infect and spread among mammals, their historically high mortality rate in humans, and the general lack of immunity in the human population.

• Although the current risk of infection for the public remains low, Health Canada recently authorized an H5N1 influenza vaccine that may benefit certain people with increased risk of exposure to the virus, such as those who work with the virus in laboratory settings or are involved in culling infected poultry, as an added layer of protection in addition to other preventive measures.

• Ongoing monitoring of the immune response to H5 influenza vaccines against circulating avian influenza strains will help to inform whether updated vaccines are needed.

In 2024 in the United States, avian influenza A(H5N1) clade 2.3.4.4b was detected for the first time in dairy cattle, an unexpected and previously unrecognized host, with subsequent transmission to dairy farm workers. As dairy cattle and poultry farm outbreaks continue, reported human H5N1 infections in the US have risen to 70 cases and 1 death, primarily linked to occupational exposure. Less frequently, infections have also occurred through contact with infected backyard poultry flocks or from unidentified exposures.1

In Canada, the virus has been detected in wild birds in every province and territory, as well as in poultry and in wild mammals in most regions.2 Although the current risk of infection for the public remains low, people with prolonged or close (within 2 m) contact with infected animals or their secretions face a moderate risk of infection, and the potential for more severe infections is considered greater for children and immunocompromised adults.3 Health Canada recently authorized an H5N1 vaccine that may benefit certain people with increased risk of exposure to the virus, as an added layer of protection in addition to other preventive measures. We discuss historical and present patterns of H5N1 infection, the virus’s potential for pandemic spread among humans, and public health measures, including vaccination.

(SNIP)

In Canada, surveillance is ongoing to detect infections in dairy cattle, including milk testing, but to date, none have been found. Measures to prevent infection in people who work with infected animals include use of personal protective equipment, biosecurity protocols, and antiviral postexposure prophylaxis. Front-line health care providers should be familiar with risk factors for exposure to avian influenza, especially close or prolonged contact with infected farmed poultry, backyard flocks, or farmed or wild mammals or their environments. Influenza testing and isolation should be recommended for those with influenza-like illness and potential risk of avian influenza exposure.5

With respect to vaccination, in February 2025, Health Canada authorized a strain update to the Arepanrix H5N1 vaccine for use in people aged 6 months and older, with 2 doses administered at least 3 weeks apart.6 The vaccine targets the H5N1 clade 2.3.4.4b viruses currently circulating in birds and mammals in North America. The Government of Canada purchased an initial 500 000 doses. Based on current evidence and expert opinion, Canada’s National Advisory Committee on Immunization (NACI) recommended to provincial and territorial health authorities that the vaccine could be considered for use in populations at increased risk of exposure to the virus, such as those who work with the virus in laboratory settings or those involved in culling infected poultry.7 Ultimately, the provinces and territories will decide how to deploy their allocated vaccine, guided by NACI recommendations, but the specific approaches are yet to be determined.

(SNIP)

As Canadian jurisdictions plan how they will use the current supply of H5N1 vaccine in the context of local risk conditions, experts continue to monitor and conduct research to fill existing knowledge gaps.9 Recent outbreaks and detections of avian influenza H5N2 and H5N5 in poultry in Canada raise the question of whether an H5N1 vaccine could provide protection against rapidly evolving avian influenza viruses. Limited evidence suggests that crossreactive immunity is expected from the H5 component of the vaccine, irrespective of the neuraminidase type, unless there is substantial evolution of the H5 of circulating strains. (The contribution of the neuraminidase components of vaccines to the immune response is an area of active scientific investigation.) A preprinted serologic study of a small sample of H5N8 vaccine recipients in Finland suggests that the vaccine elicited a good immune response to H5N1 clade 2.3.4.4b viruses, representative of currently circulating strains.10 Ongoing monitoring of the immune response against circulating avian influenza strains will help to inform whether updated vaccines are needed.

(Continue . . . )

EID Journal: Evidence of Viremia in Dairy Cows Naturally Infected with Influenza A Virus, California, USA

 

#18,741

Even though we are now more than 14 months, and over 1,070 infected dairy herds, since the discovery of HPAI H5N1 in dairy cows there is still much we don't know about how the virus is spreading. Testing of cattle has been limited, is generally voluntary, and is focused almost exclusively on lactating dairy cows. 

A recent study suggests the virus is far more widespread in livestock than has been reported (see Nature: A Mathematical Model of H5N1 Influenza Transmission in US Dairy Cattle) and serological data suggest some human infections are likely going unreported (see MMWR: Serologic Evidence of Recent Infection with HPAI A(H5) Virus Among Dairy Workers). 

Many dairy farmers - fearing loss of income or the stigma of infection - simply prefer a `Don't test, don't tell' strategy. We've also seen farm workers reluctant to report illnesses, or be tested for the virus, over fears of losing their jobs (see EID Journal: Avian Influenza A(H5N1) Virus among Dairy Cattle, Texas, USA).

The USDA's  Dairy Herd Status Program website hasn't been updated in 5 weeks (Apr 25th), and continues to show just 100 herds (out of an est. 36,000) from 18 states enrolled in the voluntary herd monitoring program. 

Over the past year we've also seen spillovers of H5N1 into goats, alpacas, pigs, and most recently a sheep in the UK. Despite very limited surveillance, we've also seen hundreds of peridomestic animals (cats, foxes, mice, etc.) infected in and around dairy farms and in the wild. 

It seems likely we are only seeing the tip of the H5N1 iceberg. 

While the prevailing theory is that HPAI mainly affects lactating dairy cows - and is due to the virus's affinity to bovine mammary cells - very little testing of beef cattle has been undertaken.  

At least one study (see Virology: Detection of Antibodies Against Influenza A Viruses in Cattle) has recently reported that bulls and steers were just as likely to carry antibodies to (non-HPAI H5) IAV as cows and heifers.

Today we have a dispatch, published on Friday in the CDC's EID journal, which raises new questions on how HPAI might be spreading among cattle, as it finds evidence of viremia in a number of cows they tested. 

Until now, evidence of IAV viremia in cows has been scant. Admittedly, most studies have focused on viral detection in milk, mammary tissues, and less often; respiratory tissues. 

If today's findings prove to be commonplace, it raises new questions as to how the virus may be spreading, and even potential risks to the food supply 

Due to its length, I've only posted the link and some extended excerpts (emphasis mine).  Follow the link to read the report in its entirety, as it raises some very interesting questions. 

Volume 31, Number 7—July 2025

Dispatch

Evidence of Viremia in Dairy Cows Naturally Infected with Influenza A Virus, California, USA

Jason Lombard , Chloe Stenkamp-Strahm, Brian McCluskey1, and Blaine Melody

Abstract

We confirmed influenza A virus (IAV) by PCR in serum from 18 cows on 3 affected dairy farms in California, USA. Our findings indicate the presence of viremia and might help explain IAV transmission dynamics and shedding patterns in cows. An understanding of those dynamics could enable development of IAV mitigation strategies.


In March 2024, the United States Department of Agriculture’s National Veterinary Services Laboratories (NVSL) confirmed avian influenza virus (IAV) A(H5N1) clade 2.3.4.4b in dairy cows in Texas, USA (1,2). That subtype was further characterized as genotype B3.13. Since that detection, >1,070 herds in 17 states have been affected; most of those herds are in California (3). Clinical signs observed have been variable, but fever, nasal discharge, loss of milk production, and mastitis are common (4).

Experimental and field investigations into the transmission dynamics, pathogenesis, and epidemiology of H5N1 virus in cows are ongoing. Researchers have inoculated cows via the intramammary route in 3 studies, and resulting clinical signs were similar to those from field reports of affected cows, including severe disease requiring euthanasia. Viral RNA was found in milk samples in all studies (5–7) but in blood samples in only 1 study (7).

Early in the ongoing outbreak, nasal swab, whole blood, serum, and milk samples were collected from affected dairies in Texas, New Mexico, Kansas, and Ohio. Viral RNA was detected in nasal swab (10/47 cows), whole blood (3/25 cows), serum (1/15 cows), and milk (129/192 cows) samples (4).

We sampled cows using a serial sampling design early in the outbreak on affected dairy farms in California. We report detection of IAV RNA in serum samples from lactating dairy cows.

          (SNIP)

Conclusions

Our results suggest that a percentage of lactating cows on dairies affected by H5N1 virus experience viremia before or during the peak of clinical cases in the herd. We detected viral RNA in serum of each PCR-positive cow at a single sample date. Viremia therefore appears to be transient, but the duration is unknown because cows were not sampled daily.

Although the finding of viremia does not specify how IAV made it to the bloodstream, virus present in circulation suggests that multiple exposure pathways might be possible, including oral and respiratory routes. Intramammary inoculation studies have shown viral RNA to be in multiple tissues at necropsy (6,7), although viremia had not been consistently detected.

Viremia enables virus to reach many tissues in the body, including the kidneys, which is evident in this study given detectable RNA in urine samples. That process raises concern for food safety and whether viremia could lead to the presence of H5N1 virus in meat from culled dairy cows.

A study that evaluated condemned carcasses found viral RNA in 1 of 109 total samples (8). Further, an aborted fetus from farm B, not from a known viremic cow, was positive for H5N1 virus in lung and brain tissue by PCR and immunohistochemical staining. H5N1 virus can move into the reproductive tract and is associated with abortion, which also has implications for the use of fetal serum products.

All cows in this study had IAV detection in serum and milk, so it is unclear whether intramammary infection led to viremia or viremia led to intramammary infection. Three cows classified as healthy had viral RNA detected in serum, and 1 of the 3 had viral RNA detected in serum and urine. The relationship between viremia and clinical signs is therefore unclear, although we might have sampled those cows before the onset of clinical disease.

Determining whether the viremia we detected is a rare event is crucial. Viremia has only been detected in 1 previous H5N1 intramammary experimental infection study and 1 field study. To clarify the frequency of viremia, more studies that evaluate IAV RNA in the serum of cattle should be completed.

The prevalence of viremia detected in the Jersey breed herd compared with the 2 Holstein breed herds suggests breed differences in susceptibility to viremia from IAV infection might be involved, but differences in cow selection by farm might have affected prevalence. We also recommend a genetic comparison of viral strains collected between studies and between states.

Viremia in California dairy cows could be the result of viral evolution, because viremia was not well documented previously, and experimental studies used a strain of H5N1 virus from the early stages of this outbreak. Further in-depth studies that include viral sequencing are necessary to strengthen the evidence supporting our conclusion.

In summary, findings of IAV in serum of cows on farms in California indicates the presence of viremia and could help explain viral transmission dynamics and shedding patterns in cows. Understanding such dynamics could help in development of mitigation strategies to prevent transmission and spread of IAVs, including H5N1 virus.

Dr. Lombard is a veterinary epidemiologist at Colorado State University, Fort Collins, CO, USA. His research interests are infectious diseases of cattle.

This study hints at something we've discussed often. The unseen impacts of long chains of infection over time; in cattle, other livestock, and in peridomestic animals (mice, cats, birds, etc.) that may be exposed to infected cattle.   

Like a classic serial passage experiment (see above), the virus that emerges at the end of a long chain of infections may differ greatly from the wild-type virus at the start.  Most will be evolutionary duds, but occasional a more biologically `fit' virus will emerge. 

Sadly, our current passive and selective (usually voluntary) testing is unlikely to show us what changes may be occurring in real time. 

Which places us at very real risk of being caught short when something more virulent, or more transmissible, finally does emerge.   

CFIA Update On H5N1 In a B.C. Ostrich Farm: First Report of Genotype D1.3 in Canada

WOAH/OIE 
 

#18,740

Last December an ostrich farm in British Columbia reported unusual mortality among their birds, and in early January HPAI H5N1 was confirmed by the CFIA. 

That agency order culling - the long-standing  recommendation of WOAH/OIE (see below) - of the remainder of the exposed birds.

Control strategies and compensation for farmers

When an infection is detected in poultry, a policy of culling infected animals and the ones in close contact is normally used in an effort to rapidly contain, control and eradicate the disease.

Selective elimination of infected poultry, movement restrictions, improved hygiene and biosecurity, and appropriate surveillance should result in a significant decrease of viral contamination of the environment. These measures should be taken whether or not vaccination is part of the overall strategy. 

The farm owners have fought a protracted legal battle to prevent this culling, which has become a cause célèbre online, and in the political arena.  

Yesterday the CFIA published an update which adds a new wrinkle to this 5-month saga; the announcement that (at least some of) these ostriches were infected with a novel genotype (D1.3), which was identified in a sick Ohio poultry worker last February. 

Although more than 100 genotypes of H5N1 have been reported in North America since the H5 virus arrived in late 2021, over the past 15 months we've seen 4 new genotypes of note emerge in the United States and Canada.

• B3.13 aka the `bovine' strain affecting dairy cattle in at least 16 states and mildly infecting dozens of humans
• D1.1   a wild bird/poultry strain which has spilled over into > a dozen people in Washington State, severely infected a teenager in British Columbia, and produced a fatal infection in Louisiana. 
• D1.2  a wild bird/poultry strain which recently detected in poultry and 2 pigs in Oregon
• D1.3  a recently detected wild bird/poultry strain which has been infection poultry and at least 1 human

While we are only hearing about it 5 months after-the-fact, this first reported outbreak of genotype D1.3 in Western Canada pre-dates the Ohio outbreak by a couple of months.

While much of this announcement centers on the government's case for culling these birds, what arguably should have been the lede (in red) is buried about 1/3rd  the way down the page. 

Update on the Canadian Food Inspection Agency's actions at an HPAI infected premise at a British Columbia ostrich farm

From: Canadian Food Inspection Agency

Statement

The Canadian Food Inspection Agency (CFIA) and Canada's national poultry sectors have been responding to detections of highly pathogenic avian influenza (HPAI) in Canada since December 2021. Industry has been highly supportive of the CFIA in its response to HPAI, working collaboratively to implement control measures and protect animal health.

The CFIA has acted to minimize the risk of the virus spreading within Canadian flocks and to other animals. All avian influenza viruses, particularly H5 and H7 viruses, have the potential to infect mammals, including humans. Our disease response aims to protect public and animal health, minimize impacts on the domestic poultry industry, and the Canadian economy.

The CFIA's response to highly pathogenic avian influenza in domestic poultry is based on an approach known as “stamping-out”, as defined by the World Organisation for Animal Health (WOAH) Terrestrial Animal Health Code. Stamping-out is the internationally recognized standard and is a primary tool to manage the spread of HPAI and mitigate risks to animal and human health as well as enable international trade. It includes steps to eliminate the virus from an infected premises, including the humane depopulation and disposal of infected animals, and disinfection of premises.

There are ongoing risks to animal and human health and Canada’s export market access

Allowing a domestic poultry flock known to be exposed to HPAI to remain alive means a potential source of the virus persists. It increases the risk of reassortment or mutation of the virus, particularly with birds raised in open pasture where there is ongoing exposure to wildlife.

CFIA’s National Centre for Foreign Animal Disease (NCFAD) identified that the current HPAI infection in these ostriches is a novel reassortment not seen elsewhere in Canada. This assortment includes the D1.3 genotype, which has been associated with a human infection in a poultry worker in Ohio.

A human case of H5N1 in BC earlier this year required critical care, and an extended hospital stay for the patient, and there have been a number of human cases in the United States, including a fatality.

Stamping-out and primary control zones enable international trade as it allows Canada to contain outbreaks within a specific area, meet the requirements of zoning arrangements with trading partners, and permit Canada’s poultry industry to export from disease-free regions. Continued export market access supports Canadian families and poultry farmers whose livelihoods depend on maintaining international market access for $1.75 billion in exports.

Current status of the infected premise at Universal Ostrich Farm

Universal Ostrich Farm has not cooperated with the requirements set out under the Health of Animals Act including failure to report the initial cases of illness and deaths to the CFIA and failure to adhere to quarantine orders. Universal Ostrich Farm was issued two notices of violations with penalty, totaling $20,000.

The farm also failed to undertake appropriate biosecurity risk mitigation measures such as limiting wild bird access to the ostriches, controlling water flow from the quarantine zone to other parts of the farm, or improving fencing. These actions significantly increase the risk of disease transmission and reflect a disregard for regulatory compliance and animal health standards.

Universal Ostrich Farm has not substantiated their claims of scientific research. CFIA has not received any evidence of scientific research being done at the infected premises.

Research documentation was not provided during the review of their request for exemption from the disposal order based on unique genetics or during the judicial review process. Further, the current physical facilities at their location are not suitable for controlled research activities or trials.

On May 13, 2025, the Federal court dismissed both of Universal Ostrich Farm’s applications for judicial review. The interlocutory injunction pausing the implementation of the disposal order was also vacated.

Following the May 13 court ruling, the farm owners and supporters have been at the farm in an apparent attempt to prevent the CFIA from carrying out its operations at the infected premises. This has delayed a timely and appropriate response to the HPAI infected premises, resulting in ongoing health risks to animals and humans.

CFIA’s next steps at the infected premises

Given that the flock has had multiple laboratory-confirmed cases of H5N1 and the ongoing serious risks for animal and human health, and trade, the CFIA continues planning for humane depopulation with veterinary oversight at the infected premises.

The CFIA takes the responsibility to protect the health of animals and Canadians extremely seriously as we conduct these necessary disease control measures to protect public health and minimize the economic impact on Canada's poultry industry.

For more detailed information on the CFIA’s continued response to HPAI at this infected premises, please visit our website.

Understanding the origins and spread of novel genotypes, subtypes, and certain mutations in HPAI viruses are all critical if we hope to get some kind of control over  this growing epizootic.  

Last April Canada was singled out for being one of  the slowest nations in releasing non-human HPAI sequence information (see Nature: Lengthy Delays in H5N1 Genome Submissions to GISAID). 

Today's belated announcement only appears to further cement that reputation. 

OFID: Viral Families with Pandemic Potential

 

#18,739

For many years it was common to hear that - of all the diseases with pandemic potential - it was influenza A that kept virologists up at night.  A little over 20 years ago, the emergence of SARS-CoV forced the addition of novel coronaviruses to that short list. 

In 2017 (and again in 2018) the WHO released a list (n=8) of priority diseases (see WHO List Of Blueprint Priority Diseases) - that in their estimation had the potential to spark a public health emergency and were in dire need of accelerated research:

• Crimean-Congo haemorrhagic fever (CCHF)
• Ebola virus disease and Marburg virus disease
• Lassa fever
• Middle East respiratory syndrome coronavirus (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS)
• Nipah and henipaviral diseases
• Rift Valley fever (RVF)
• Zika
• Disease X

Last summer the WHO unveiled an expanded 38-page Pathogens Prioritization report, increasing the number of priority pathogens to more than 30. Additions included 7 different influenza A subtypes (H1, H3, H3, H5, H6, H7, and H10), and 5 bacterial strains that cause cholera, plague, dysentery, diarrhea and pneumonia.

Thirty years ago researcher George Armelagos of Emory University posited that since the mid-1970s the world had entered into an age of newly emerging infectious diseases, re-emerging diseases and a rise in antimicrobial resistant pathogens (see The Third Epidemiological Transition (Revisited). 

And the following timeline, from the UK HAIRS group would seem to support that theory.

UK HAIRS Timeline - 20 years of Emerging Viruses

Nature, it seems, has a nearly inexhaustible supply of replacement viral contenders (see mBio: A Strategy To Estimate The Number Of Undiscovered Viruses), and what doesn't succeed today can always mutate and try again tomorrow. 

Today we've a perspective, published in Open Forum Infectious Diseases, by two well known infectious disease experts (Amesh Adalja, MD FIDSA & Thomas Inglesby, MD) from Johns Hopkins Center for Health Security, that proposes - in addition to Influenza A and Coronaviruses - that 4 other viral families be considered as having significant pandemic potential. 

• Picornaviridae     (e.g. rhinoviruses, EV-71, EV-D68, etc)
• Paramyxoviridae (e.g. HPIV, Nipah, measles, etc.)
• Adenoviridae        (e.g. Ad14, Ad7)
• Pneumoviridae     (e.g. Metapneumovirus, hRSV, etc.) 

Although there are certainly other viral families with pandemic potential, the authors of this perspective focus on viruses which currently have limited or no medical countermeasures (MCMs).  While it's not a long article, I've only posted a few excerpts.

Follow the link to read it in its entirety.  I'll have a bit more after the break. 

Viral Families with Pandemic Potential

Open Access
Amesh Adalja, MD FIDSA , Thomas Inglesby, MD
Open Forum Infectious Diseases, ofaf306, https://doi.org/10.1093/ofid/ofaf306

Published: 26 May 2025 Article history

A major challenge of pandemic preparedness is how to anticipate and prepare for future pandemic threats among the wide range of viral threats that can infect humans. Fortunately, only a subset of the 25 viral families that can infect humans have both the capability of widespread respiratory transmission in humans or animals, a prerequisite for pandemic-causing capability, as well a lack of medical countermeasures (MCMs) to prevent and treat the key viral species within them. 

Orthopoxviruses, for example, clearly have historically shown the capacity to cause terrible pandemics in humans, but there exist vaccines and antivirals that have been developed and stockpiled for this viral family that are cross protective against multiple family members (unlike the case for the pandemic-causing orthomyxoviruses and coronaviruses). 

Therefore, for the purposes of identifying novel rapid-onset novel pandemics, they are not listed here as a viral family of pandemic potential with unmet R&D requirements though there is clear need for improved countermeasures to both of these viral families. 

Prior to COVID, most pandemic preparedness efforts, when they did occur, focused almost exclusively on influenza viruses. Pandemic preparedness was considered to be nearly synonymous with influenza preparedness. This has basis in experience as the only occurring pandemics for almost a century (spanning from at least 1918 to 2009) were all caused by influenza A viruses. However, a number of events of the past 20 years have shown the capacity of coronaviridae to cause major epidemics and pandemics: SARS—CoV-1 in 2003, MERS-CoV in 2012, and, most recently and obviously, SARS-CoV-2 in 2019-2020.

It is critical now to plan for other viral threats that can cause huge epidemics or pandemics. We were one of the first to publish on the characteristics of pandemic pathogens, and in that effort, we emphasized conceptualizing the problem by putting specific focus on viral families of  greatest pandemic potential, particularly families for which no MCMs were yet developed [1,2]. 

          (Continue . . . )

Over the years we've looked at dozens of threats from these four viral families, including:

• EID Journal: Henipavirus in Northern Short-Tailed Shrew, Alabama, USA
• EID Journal: Emerging Enterovirus A71 Subgenogroup B5 Causing Severe Hand, Foot, and Mouth Disease, Vietnam, 2023
• India: Media Reports Of A Large Surge In Pediatric Adenovirus Infections 
• NEJM: A Novel Henipavirus With Human Spillover In China
• mBio: Contemporary EV-D68 Strains Have Acquired The Ability To Infect Human Neuronal Cells

While it's true that the vast majority of  these viruses will never fulminate into any kind of global health threat, COVID-19 showed it only takes one overachiever to plunge the world into chaos.  

Although severe pandemics were once thought to come along every few decades, recent studies suggest that the frequency, and impact, of pandemics are only expected to increase in the years ahead.

BMJ Global: Historical Trends Demonstrate a Pattern of Increasingly Frequent & Severe Zoonotic Spillover Events

PNAS Research: Intensity and Frequency of Extreme Novel Epidemics

Which means that while we can try to ignore these threats, at some point time our luck - and time - will run out. 

Moderna Announcement: HHS Cancellation of HHS Late-Stage Contract To Provide mRNA H5 Vaccine

 

Credit ACIP/CDC

#18,738

Just over a year ago, in response to the detection of H5N1 in diary cattle, the HHS contracted with CSL Seqirus for 4.8 million doses of a cell-based, adjuvanted, H5 vaccine (using the Astrakhan H5 antigen); enough for about 2.4 million people.

As the H5 threat increased over the fall and winter months, last January the outgoing administration awarded Moderna a $590 Million Dollar Contract To Develop an mRNA H5N1 Vaccine.  Almost immediately, the incoming administration announced they would be reviewing that contract. 

Despite an excellent safety record, and the added ability to produce large quantities of updated vaccine quickly without relying on antiquated egg-based manufacturing techniques - many people distrust mRNA vaccines; some vehemently. 

Admittedly, no vaccine is 100% or benign. With all medicines, there is a risk/benefit calculation to be made, and in most cases the benefits far outweigh any risks. 

Overnight Moderna posted the following announcement, providing an encouraging early update on  immune responses from the vaccine, followed by the HHS cancellation of the January contract. 

Moderna Announces Update on Investigational Pandemic Influenza Program

May 28, 2025

Phase 1/2 H5 avian flu vaccine study shows positive interim results

Company has been notified that HHS will terminate Moderna's award for late-stage development of pre-pandemic influenza vaccines

CAMBRIDGE, MA / ACCESS Newswire / May 28, 2025 / Moderna, Inc. (NASDAQ:MRNA) today announced positive interim data from a Phase 1/2 clinical study (NCT05972174) evaluating the safety and immunogenicity of its investigational pandemic influenza vaccine, mRNA-1018, in approximately 300 healthy adults aged 18 years and older. The interim results focus on a vaccine candidate targeting the H5 avian influenza virus subtype.

The Company had previously expected to advance the program to late-stage development with the U.S. Department of Health and Human Services (HHS); however, today Moderna received notice that HHS will terminate the award for the late-stage development and right to purchase pre-pandemic influenza vaccines.     

(SNIP)

The Phase 1/2 study evaluated a two-dose regimen of Moderna's investigational avian influenza vaccine. mRNA-1018 demonstrated a rapid, potent and durable immune response. At baseline, pre-existing immunity was minimal, with only 2.1% of participants showing hemagglutination inhibition (HAI) antibody titers ≥1:40, an HAI titer considered to correlate with protection. At Day 43, three weeks after the second vaccination, 97.8% of participants achieved titers ≥1:40 with a 44.5-fold increase of titers from baseline.

The investigational vaccine was generally well-tolerated, with no dose-limiting tolerability concerns observed. Most solicited adverse reactions were Grade 1 or 2 and did not increase significantly with number of doses or between first and second doses. Further data is expected to be submitted for presentation at an upcoming scientific meeting.

         (Continue . . . ) 

The production and deployment of emergency vaccines for a pandemic is often fraught with delays and uncertainty, which makes pre-planning all the more important.

Early experimental H5 (and H7) avian flu vaccines proved poorly immunogenic – requiring unusually large amounts of antigen (up to 12x normal). Adding an adjuvant - spread across two shots several weeks apart - produced a much better immune response (see 2015's JAMA: Immune Response Of H7N9 Vaccine With & Without Adjuvant).

The United States approved an adjuvanted monovalent H5Nx vaccine from Seqirus back in early 2020 (see FDA approval letters), despite concerns over whether Americans will accept an adjuvanted vaccine (which have been used successfully in Europe for years).

 

We've also seen difficulties in producing bulk H5N1 vaccines in the past, particularly in egg-based production facilities (see Manufacturing Pandemic Flu Vaccines: Easier Said Than Done).  And of course, because of our current poultry epizootic, the supply of eggs in which to make a vaccine could become a problem.

Even under the best reasonable scenario - using both egg and cell-based technology - it could take months into a pandemic before a vaccine would be widely available (see Maggie Fox's  SCI AM - A Bird Flu Vaccine Might Come Too Late to Save Us from H5N1). 

According to recent polls (see Two Surveys (UK & U.S.) Illustrating The Public's Lack of Concern Over Avian Flu), most people don't consider HPAI H5 to be a major public health threat.  And it is possible they are right. H5Nx could certainly fizzle, or be overtaken by another threat. 

I only know that there are a lot of viral contenders out there, and another pandemic is inevitable.

And as we discussed in The Wrong Pandemic Lessons Learned, the world seems to be less well prepared today for another pandemic than we were a decade ago. 

While a course correction is badly needed, I fear we may not see one until the pandemic-after-next.

WHO DON: Global COVID Situation (May 28th, 2025)

 

#18,737

Over the past few weeks we've been seeing reports of increasing COVID activity, particularly in Asia, and three days ago we looked at a WHO Risk assessment on a recently emerged variant (see WHO TAG-VE Risk Assessment On COVID VUM (Variant Under Monitoring) NB.1.8.1) that is behind some of this surge.

As we've discussed ad nauseum over the past few years (see here, here, here, here, etc.), 90% of the world's nations no longer report COVID hospitalizations or deaths, making it very difficult to track changes in the evolution and behavior of new variants. 

Despite evidence that repeated COVID infections increase the risks of developing `long COVID', and other sequelae (see Brain, Behavior & Immunity: COVID-19 may Enduringly Impact Cognitive Performance and Brain Haemodynamics in Undergraduate Students), governments around the globe have opted to minimize the threat, in order to `move on' from the pandemic.

While the WHO still produces a monthly COVID-19 epidemiological report, today they've published an unusual post-pandemic DON (Disease Outbreak News) update on the global COVID situation. 

The rub is, they cite `very limited data' submitted by member countries as preventing them from being able to fully evaluate the impact of this new wave. 

Despite these challenges, the WHO states the `global public health risk associated with COVID-19 remains high'.

I've only posted some excerpts from the report, so follow the link to read it in its entirety.   I'll have a postscript after the break. 

COVID-19 - Global Situation
28 May 2025

Situation at a glance 

Since mid-February 2025, according to data available from sentinel sites, global SARS-CoV-2 activity has been increasing, with the test positivity rate reaching 11%, levels that have not been observed since July 2024. This rise is primarily observed in countries in the Eastern Mediterranean, South-East Asia, and Western Pacific regions.

Since early 2025, global SARS-CoV-2 variant trends have slightly shifted. Circulation of LP.8.1 has been declining, and reporting of NB.1.8.1, a Variant Under Monitoring (VUM), is increasing, reaching 10.7% of global sequences reported as of mid-May. Recent increases in SARS-CoV-2 activity are broadly consistent with levels observed during the same period last year, however, there still lacks a clear seasonality in SARS-CoV-2 circulation, and surveillance is limited. Continued monitoring is essential. WHO advises all Member States to continue applying a risk-based, integrated approach to managing COVID-19 as outlined in the Director-General’s Standing Recommendations [1]. As part of comprehensive COVID-19 control programmes, vaccination remains a key intervention for preventing severe disease and death from COVID-19, particularly among at risk groups. 

Description of the situation

There has been an increase in SARS-CoV-2 activity globally, based on SARS-CoV-2 data reported to the Global Influenza Surveillance and Response System (GISRS) from sentinel surveillance sites. As of 11 May 2025, the test positivity rate is 11% across 73 reporting countries, areas and territories. This level matches the peak observed in July 2024 (12% from 99 countries) and marks a rise from 2% reported by 110 countries back in mid-February 2025 (Figure 1). The increase in test positivity rate is mainly being driven by countries in the Eastern Mediterranean Region, the South-East Asia Region, and the Western Pacific Region.

Countries in the African Region, European Region, and the Region of the Americas are currently reporting low levels of SARS-CoV-2 activity with percent positivity from sentinel or systematic virological surveillance sites ranging from 2% to 3%. However, some areas—particularly in the Caribbean and Andean subregions in the Region of the Americas showed increasing trends of SARS-CoV-2 test positivity as of 11 May. Publicly available wastewater monitoring data from countries in the European Region and the Northern America subregion remain low and, at present, do not indicate any upward trend in SARS-CoV-2 activity as of 11 May 2025.

The reporting of COVID-19 associated hospitalizations, Intensive Care Unit (ICU) admissions, and deaths is very limited from the countries in the Eastern Mediterranean Region, the South-East Asia Region, and the Western Pacific Region and does not allow for evaluation of the impact on health systems by WHO.

          (SNIP)

WHO risk assessment

As per the latest WHO global risk assessment, covering the period July-December 2024, the global public health risk associated with COVID-19 remains high. There has been evidence of decreasing impact on human health throughout 2023 and 2024 compared to 2020-2023, driven mainly by: 1) high levels of population immunity, achieved through infection, vaccination, or both; 2) similar virulence of currently circulating JN.1 sublineages of the SARS-CoV-2 virus as compared with previously circulating Omicron sublineages; and 3) the availability of diagnostic tests and improved clinical case management.

SARS-CoV-2 circulation nevertheless continues at considerable levels in many areas, as indicated in regional trends, without any established seasonality and with unpredictable evolutionary patterns. WHO produces global COVID-19 risk assessments every six months; the global risk assessment covering the period January-June 2025 is currently under development.

WHO continues to monitor emerging SARS-CoV-2 variants and undertakes risk evaluation for designated variants of interest (VOI) and VUMs with the support of the Technical Advisory Group of Virus Evolution (TAG-VE). Evaluation of the currently predominant VUM, LP.8.1, and the most recently designated VUM, NB.1.8.1, suggests no increased public health risk posed by these variants compared to other circulating variants.

To permit robust COVID-19 risk assessment and management, WHO reiterates its recommendations to Member States to continue to monitor and report SARS-CoV-2 activity and burden, public health and healthcare system impacts of COVID-19, strengthen genomic sequencing capacity and reporting, in particular information on SARS-CoV-2 variants [6], promptly and transparently to support global public health efforts.

          (Continue . . . )

While predicting what COVID will do next is a mug's game, we do know that COVID `immunity' - whether acquired from vaccines or infection - wanes over time, and vaccine uptake has continued to fall both here in the United States, and in many countries around the globe.

A summer surge is certainly possible.  And even if this latest variant proves to be no more virulent than previous Omicron strains, repeated infections are problematic. 

Which is why I got my 6-month COVID booster in April, and why I'll continue to wear an N95 mask in crowded, indoor, venues.  Neither guarantee I'll stay infection free, but they do improve my chances.