[Notes] Current State of H5N1
Notes from NTI | bio’s event with Dr. Lu Borio on July 18, 2024: “A Conversation with Dr. Luciana Borio on H5N1 Bird Flu”
Dr. Lu Borio is a member of the NTI Board of Directors, a specialist in biodefense, emerging infectious diseases, medical product development, and complex public health emergencies.
Alo a Venture Partner at ArchVenture Partners, a Senior Fellow for Global Health at the Council on Foreign Relations, and an Adjunct Assistant Professor of Medicine at Johns Hopkins University
Serves on the boards of Noblis, Insulet, and Eagle Pharmaceuticals
Was Senior Vice President at In-Q-Tel, as a member of President Biden's Transition COVID-19 Advisory Board, and as Director for Medical and Biodefense Preparedness on the National Security Council
Also served as Acting Chief Scientist of the U.S. Food and Drug Administration and is the Assistant Commissioner for Counterterrorism Policy at FDA.
Background of H5N1
Emerged in early 2022, affecting wild birds and commercial agriculture in North America
Spread to 97 million birds in the US and millions globally over the next 2 years
H5N1 outbreak 2024
Earlier this year, dairy cows began showing strange symptoms (low appetite, reduced milk production, discolored and thickened milk production), prompting health authorities to test cattle.
First outbreak among cattle detected in Texas Panhandle region in March 25, spread to 12 states (we now know it remained undetected since Dec 2023). Affected more than 160 herds (an underestimate; farmers still refusing to test/report under-testing/under-reporting)
Cases among humans remain low, with nine confirmed cases since 2022
Outbreak has affected mammals mostly so far, but remember 2009 bird flu spread quietly in pigs, which led to H1N1 flu pandemic (believed to have caused hundreds of thousands of deaths globally)
Human cases - concern is on April 1, Texas reported first confirmed human H5N1 infection associated with this outbreak → dairy farm worker who developed eye symptoms conjunctivitis i.e. pink eye
Conjunctive of eye has receptors for avian flu (so unsurprising that initial presentation was conjunctivitis)
Since then, more cases identified (incl. 5 cases last week reported in Colorado in workers involved in colon-infected poultry) most experiencing eye infection; but now have shown respiratory symptoms more chracteristic of flu → indicating virus can now infect lower airways
Current public health response
US CDC assesses public health risk as low but is concerned about potential zoonotic spillover, remains vigilant due to recent human cases in Colorado
Lessons from COVID-19 emphasize the need for proactive and forward-leaning measures
Global Health Security Index indicates all countries lack critical capacities for pandemic response – despite coming from COVID world is dangerously unprepared to respond
USDA recent studies have shown cows can get infected through aerosol route (like through mist containing virus) even if what’s driving outbreak seems to be exposure to the milking equipment that is contaminated; & virus concentrates in large amounts in the milk of these dairy cows
Recent University of Zurich study – another flu virus can enter cells through a different mechanism (second entry pathway)
Yoshihiro Kawawoka's group at the University of Wisconsin-Madison (well-respected flu lab) found that H5N1 virus circulated in cattle may be able to bind to receptors along the human upper respiratory tract more avidly than expected.
Some criticized lab assays used, experiments done, but well-respected lab, impt to approach findings with dose of respect
2 mutations on virus protein (to be exact) can allow virus to much more avidly bind to human area receptors
Bottom line = virus can totally surprise us
Dr Lu alarm bells: science, gov’t, public trust to gov’t and public health
Science - Virus adaptation and mutation:
H5N1 could adapt to infect humans more efficiently
Federal officials' statements on low risk of adaptation may underestimate potential threat. Dr. Lu a bit anxious when fed gov’t officials say they aren’t seeing concerning markers for adaptation, for male adaptation, because the fact is that the virus is infecting mammals quite well.
Regardless what you see in lab, real-life expt is being done.
Each mammal-to-mammal transmission increases the risk of the virus adapting
Government - Gov’t response and preparedness
It’s a political year – tempting to wish threat away than risk alarming public and backlash
Reluctance to declare public health emergency due to political and public fatigue (e.g. public fatigue from COVID, farms resistance to cooperate in many instances, risk over-indexing response on COVID)
Importance of rebuilding testing and clinical trial infrastructure dismantled post-COVID.
Scientific and medical preparedness
Existing H5 vaccines in stockpile offer limited cross-protection
Can’t over-rely on COVID lessons/vaccines/antivirals e.g. CDC and FDA have been testing H5 vaccines in stockpile on ferrets
Dr. Lu fr scientific perspective disagrees that they offer cross-protection (what CDC and FDA say)
Goal is not to protect against circulating virus today, but the one that could become a pandemic
Even if we have vaccines that can neutralize current virus, fact is not everyone is going to respond.
Not everyone is going to respond to vaccines, will take even at least 2 doses to achieve protection.
Can’t act like problem is solved
Need for development of more effective vaccines, including exploring mRNA platforms
Gov’t now working with mRNA developers incl. Moderna, award from HHS to produce mRNA H5 vaccines (remember mRNA is a platform, not vaccine)
mRNA worked well with COVID because immunogen worked well paried with mRNA; H5N1 is a bit trickier to achieve nice immune response to antigen
Despite great platform, doesn’t mean great vaccine yet
Current antiviral drugs like Tamiflu have limited efficacy, specifically for severe cases
Difficult to develop effective antiviral drugs for flu
Research involving monoclonal antibodies, hyperimmune globulin, sed in COVID and are used for many other infections, have not worked out so well for flu in the past
No guarantee what helped us in the past will continue to help with H5 – approach with cautious optimism
Public trust and cooperation
Essential for government, public health, scientists, and farmers to work together
Fatigure – addressing public mistrust and exhaustion from previous pandemics
Call to action
Urgent need for clear-eyed understanding and characterization of the outbreak
Need to understand better what’s going on
Michigan just began doing serology studies to identify the scope of the outbreak
How many people might’ve been exposed we don’t know about? Just beginning to do those studies
Reestablishing robust surveillance and testing systems
Need coordinated trials to know what therapeutics work, what can be repurposed, what’s performance of existing antivirals
Need to do this in a way more vigorous than last time
Encouraging scientific curiosity and humility; willingness to adapt strategies as new information emerges
We’re making lots of assumptions right now
E.g. been push for PPE in farms; but know it’s very difficult to implement PPE use in heat and occupational conditions
Preparedness on paper is not preparedness in real life
Timing matters, uptake matters (just cuz something is in stockpile doesn’t mean it can be used when needed)
Strengthening decision-making processes and international cooperation (clear processes for making critical decisions, including potential vaccination of cattle and workers)
Need to be focused on logistics of response
Figure out incentives to have more farms interested in participating in the response
Unclear: who will make the difficult calls that a pandemic would require; or pre-pandemic, who would make the call that we ought to be vaccinating cattle with an H5 vaccine?
There've been calls to vaccinate dairy workers potentially, and some countries in Europe have began to implement this
Don’t have full clarity on how new Office of Pandemic Preparedness at the White House is organized to make these types of decisions across the U.S. government
“We can't forget that the world is watching. If this becomes a pandemic, it will be highly embarrassing that we have wasted so much precious time to take more assertive action to ascertain and to respond to this outbreak.”
Final thoughts – Dr. Lu has confidence in scientific capabilities to develop vaccines and conduct clinical trials; talks of need to organize effectively to minimize loss of life and respond promptly to future public health emergencies
Important to prepare for potential pandemics
There is minimal penalty for taking proactive measures
Crises, including pandemics, tend to come and go
there is expertise in mitigating pandemic impacts, such as preventing aerosol transmission
Global science, including flu virologists and vaccine manufacturers, is strong. we know how to develop vaccines, conduct clinical trials, and make diagnostic tests
Effective global organization is essential to minimize loss of life in a pandemic
Preparation is crucial, and efforts to prepare for pandemics are foundational for responding to any large public health emergency
Q&A
Who is responsible for the actions needed to mitigate the H5N1 risk? What roles do the U.S. federal, state, and local governments play?
All the response is local
BARDA has a way within HHS to engage private sector streamlined way
The U.S. federal government should provide leadership and resources. State and local governments handle the on-the-ground response.
CDC needs to improve engagement with the private sector for diagnostic testing
One Health approach is necessary, a little complicated; past events, there was less of a one health requirement
Is the U.S. federal government well-organized to respond to threats like H5N1 that require a cross-sectoral approach?
Not uncommon for departments and agencies to have different focus
Coordination by the White House is crucial to align different departmental goals.
CDC, FDA, etc. HHS is well-suited to handle conflicts. USDA vs HHS can go onf or a long-time without resolution
Need White House to come in and say it’s a priority
Effective response requires deconflicting different priorities within the federal government
Why have H5N1 cases in the U.S. been milder compared to the high mortality rate (~40%?) in Asia? The true denominator for estimating mortality is unclear.
Several variables, including host factors and virus detection timing, influence lethality
Early cases in Asia may have presented with milder symptoms initially, such as conjunctivitis
How much do we understand about H5N1, and what remains unknown?
Understanding of the virus is incomplete and evolving. We're not seeing a lot of massive genetic changes in the virus, and yet we're seeing different phenotypic behavior in cows and humans
Potential different routes of cell entry and binding to human receptors are being studied
Scientific methods can lead to varying results; humility and curiosity are essential in research
What about the potential reassortment with seasonal flu and stockpiling of Tamiflu and N95 masks?
Reassortment with seasonal flu could increase the infectivity of H5N1
The national stockpile has Tamiflu, but its effectiveness is limited.
N95 masks are being stockpiled, but the reliability of the supply chain is a concern
What steps are needed for better H5N1 vaccines?
Quick assessment of vaccine efficacy using hemagglutinin titers
Need for rapid post-rollout studies to confirm safety and efficacy
Exploration of mRNA platforms for potentially more effective vaccines
How to balance transparency and cooperation, given laws like Michigan’s animal HIPAA? (law which provides confidentiality to the owners of sick animals and farms that are under investigation)
Balancing privacy and public health needs is challenging
Ensuring cooperation from farmers while respecting privacy is crucial for effective response
How have the recent cases in Colorado influenced your view of the H5N1 threat?
The Colorado cases don’t change the way I’m thinking, illustrate the challenge of controlling the outbreak
The potential for spillover from cows to birds and back complicates containment efforts
What should other countries do to prepare, and comments on Finland's vaccination of poultry and fur farmers?
International coordination and preparedness are essential
Finland’s approach to vaccinating workers is reasonable (esp because of mink outbreaks anf stuff) but should be part of a research program to assess effectiveness.
How does the election year and political environment affect the federal response to H5N1?
we don't want a distraction, if you will, in a political year
Sense I have, quite a bit of work being done behind the scenes (maybe this is some wishful thinking)
See a bit here and there, contract to Moderna for mRNA vaccines
Pfizer working on this as well
Example that bothers me: shaming people that drink raw milk, the shaming, we shouldn’t be in a position of shaming people. I wouldn’t drink raw milk, but it’s not the highest risk in the grand scheme of things. Much more detrimental to smoke or drive without seatbelt
Int’l context: Given the current high geopolitical tensions, do you think this will impact our ability to cooperate with global partners to effectively respond to the next pandemic? Could these tensions affect domestic responses, such as supply chain disruptions or lack of cooperation on sample sharing?
The impact on sample sharing might be overblown since samples are available domestically
Concerns exist about the U.S. response not meeting expectations, potentially upsetting other countries
“I do think that the focus clearly has been domestic preparedness in the last few years – vulnerability bc the world does need the US to be involved and leading in these types of response. World relies on US for science, guidance, response”
CDC respected globally. Need to make sure instincts to focus domestically don’t get too ahead of us. Flu pandemic is a global crisis. In this together.
Countries that have the most resources, they always are going to win in the battle for the supply chain. Have to help build capacity globally, it does not make up for our ability to also share the resources that we have here
Other helpful H5N1 articles that have had good feedback in the community (not from NTI but from Kirs)
