The recent uptick in the number of bird flu cases in the U.S. poses a threat to public health. The country’s health department has called on biotechs to develop vaccines to mitigate the outbreak.
The Center for the Biomedical Advanced Research and Development Authority (BARDA) is forming alliances with biotechs to create vaccines to combat the ongoing spread of the virus. At least 280 million birds have been killed since October 2021, and currently, in the U.S., nearly 5,000 people are being monitored for having been exposed to animals since March, with 14 reported human cases so far, according to a report by the Centres for Disease Control and Prevention (CDC).
The recent outbreaks have been hard-hitting on poultry farms and cattle, and it also led to a temporary halt in production of fresh eggs in the U.S. by the country’s largest producer Cal-Maine Foods, Inc., earlier this year.
While the bird flu virus is not yet a pandemic, Thomas Rademacher, co-founder and chief executive officer (CEO) of Emergex Vaccines, pointed out that it is important that one is prevented.
“There’s not been a case of human to human transmission of bird flu. In other words, you can catch it from the bird but you can’t give it to your neighbor. But if you did, then it would be a pandemic, because then what it means is, it’s no longer a zoonosis that is from a bird to a human. It would be human-to-human. So that’s the issue right now,” said Rademacher. “For instance, mpox came from Prairie dogs, that’s where it came from. The point is that mpox is no longer a zoonosis. Now, it’s transmitted person-to-person.”
Before the bird flu virus – more than 100 strains exist of which five subtypes are known to have caused human infections – becomes transmitted as an aerosol, more vaccines need to be developed to potentially curb the spread.
“Once it’s transmitted in the air, you’ve got big problems,” said Rademacher.
Stay tuned for updates below on the latest advancements in bird flu vaccines, investments, and strategic partnerships aimed at addressing this pressing public health issue.
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Government decisions based on “public nervousness”: an interview with Thomas Rademacher – September 30, 2024
In an interview with Rademacher, he stated that governments aren’t doing enough to eradicate bird flu.
“Governments want to make people think that they’re doing something about a problem. In other words, you can’t really be a government and say, ‘I’m ignoring bird flu.’ A lot of the time, they have to be seen as doing something. That’s going to be based more on public nervousness than real scientific rationale,” said Rademacher.
Rademacher recounted that “we all become exposed to flu naturally,” and can create what’s called original antigenic sin. This implies that when the epitope varies slightly – the part of an antigen molecule to which an antibody attaches itself – the immune system relies on memory of the earlier infection.
“There are some bits between H5 and H1 which are the same but they’re not neutralizing, and if you make antibodies to them, you can actually make the flu worse. And that’s well established in the literature,” said Rademacher. “Cross subclass vaccinations of flu can actually make the situation worse. If you are exposed as a kid to natural human flu and then, we go ahead and vaccinate you against H5N1 (bird flu), and you actually catch bird flu, it would be worse.”
“We’ve been very vocal to say that the antibody based vaccines that are being developed for bird flu are very dangerous. If given to somebody who’s never been exposed to flu, they could prevent them from generating natural immunity to human flu. On the other hand, if you give them after they have natural immunity to human flu, and if you then catch bird flu, they could make it worse.”
Critical of antibody vaccines against the bird flu, Rademacher thinks that an approach targeting cellular immunity might do the trick.
“The way around that is to basically vaccinate somebody, which is based on something that’s common. And the only thing you can find that’s common amongst all the bird flu relies on the T cell system,” Rademacher added.
Thwarting a bird flu pandemic: can a T cell vaccine be the answer?
Scientists at Rademacher’s Emergex are developing a T priming vaccine, which is currently undergoing the regulatory pathway in the U.S. to begin clinical trials next year. T cell priming is a process by which a T cell is activated when it first encounters an antigen on an antigen-presenting cell, explained a report in Frontiers.
“Our vaccines are meant to act like natural immunity, in which case, you will then be protected for 25 or 30 years or even more,” said Rademacher. “With our vaccines, we will prime you but we don’t boost. It’s a one-shot business. And it’s like you caught the flu, and what will happen is those T cells will die off, and they (the cells) will then stay at some steady state level in an equilibrium.”
The vaccine is delivered via micro-needles and “they only work if you do them right into the skin.” Rademacher added: “It’s a painless procedure. You don’t even know it and it’s not inflammatory, and it’s like a mosquito bite.”
Meanwhile, BARDA’s recent collaborations could in fact, be part of something bigger. Let us take a look at some of the key recent moments in bird flu vaccine development.
CSL Seqirus scores $121.4 million to ramp up vaccine production – September 26, 2024
In a $121.4 million deal with BARDA, CSL Seqirus announced that it will expand its reserves of MF59 adjuvant to 40 million doses.
“MF59 adjuvant is an important part of pandemic preparedness planning as it reduces the amount of antigen required to produce an immune response, increasing the number of vaccine doses. When combined with influenza antigens in a vaccine, MF59 adjuvant is designed to enhance and broaden the body’s immune response by creating a broad, cross-reactive antibody response,” the press release read.
CSL’s vaccine Audenz, which is based on MF59 technology, was approved by the U.S. Food and Drug Administration (FDA) four years ago. It is the first cell-based, adjuvanted influenza vaccine. It has been cleared for people who are at increased risk of exposure to the influenza A virus H5N1 subtype aged six months and older. The virus in the vaccine is cultured in mammalian cells as opposed to traditional egg-based vaccines, so as to cope with the limited availability of eggs for research and development (R&D).
Meanwhile, Finland became the first country to procure CSL’s vaccines for rollout back in June. It bought the double-jab vaccines for 10,000 people, as part of a joint EU deal with CSL.
CSL’s vaccine isn’t the only one that’s been greenlit. Sanofi pasteur’s H5N1 vaccine was the first bird flu vaccine for humans to be approved by the FDA, in a collaboration with the National Institutes of Health, back in 2007, despite FDA scrutiny over its efficacy.
WHO to bring bird flu vaccine to lower-income countries – July 29, 2024
While a number of studies are ongoing in the U.S., the World Health Organization embarked on a project to accelerate accessibility of mRNA bird flu vaccines in low- and middle-income countries. Argentina-based Sinergium Biotech has joined the program to escalate production. The biotech’s H5N1 vaccines are currently in preclinical studies, and once results have been established, it aims to bolster pandemic preparedness efforts.
“This initiative exemplifies why WHO established the mRNA Technology Transfer Programme – to foster greater research, development and production in low- and middle-income countries, so that when the next pandemic arrives, the world will be better prepared to mount a more effective and more equitable response,” said Tedros Adhanom Ghebreyesus, Director-General of WHO, in a press release.
GSK strikes $1.5 billion deal with CureVac to acquire flu vaccines – July 3, 2024
Big pharma GSK took the reins of CureVac’s mRNA vaccines including its bird flu vaccine, which fell short in the race against other developers like Moderna in the past. The partnership pushes the H5N1 bird flu vaccine through early-stage clinical trials.
In exchange for its vaccine, CureVac pocketed €400 million ($447.59 million) and can secure up to €1.05 billion ($1.17 million) in milestone payments.
Moderna bags $176 million BARDA award – July 2, 2024
mRNA giant Moderna was awarded $176 million from BARDA to boost the late-stage development of its bird flu vaccine.
mRNA-1018 was tested on H5 and H7 strains at multiple doses in a two-shot regimen in a phase 1/2 trial that began last year. The vaccine is injected into the muscle. Study results are yet to be published and will inform phase 3 plans, which will be funded with the help of BARDA’s partnership program.
As cases rise, 24 companies developing vaccines for cattle, says U.S. Agriculture Secretary – June 12, 2024
In a span of less than three months, bird flu infected 90 dairy herds across 12 states in the country. The U.S. Agriculture Secretary Tom Vilsack announced that 24 companies are working to create a vaccine for cattle, in a Reuters interview. The United States Department of Agriculture (USDA) is also working in tandem with universities and research organizations to better understand the spread in order to control it. This came after the government shelled out $200 million to protect public health and test milk and animals for the virus.
CSL Seqirus vows to deliver 4.8 million vaccine doses – May 30, 2024
To support government efforts to strengthen pandemic preparedness, CSL Seqirus was assigned to complete the fill and finish process of pre-pandemic vaccines in the U.S. as part of the National Pre-Pandemic Influenza Vaccine Stockpile (NPIVS) program. It pledged to deliver around 4.8 million doses of pre-pandemic vaccine that is well-matched to the H5 of the currently circulating H5N1 strain. This is the fourth award that the influenza vaccine providers has received from BARDA in response to the surge in avian influenza (bird flu) cases over the years.
Nearly two weeks later, it was also tasked by the European Commission’s Health Emergency Preparedness and Response Authority (HERA), to provide 665,000 pre-pandemic vaccine doses for fifteen EU and EEA Member States in order to create a stockpile of vaccines.
Pfizer issues pandemic preparedness statement – May 28, 2024
As biotechs move their candidates to the clinic amid the upswing in cases, Pfizer stated in a press release, “If a vaccine is needed in an emergency pandemic situation, Pfizer anticipates that the modRNA vaccine platform could be leveraged to rapidly provide a vaccine candidate targeting the specific pandemic influenza strain.”
Pfizer’s phase 1 mRNA vaccine candidate encodes the hemagglutinin (HA) antigen of a pandemic influenza strain from the A/H5 subtype. It is designed to antigenically mirror the avian strain [H5, Clade 2.3.4.4b], which is currently causing significant disease in birds and cows and recent case reports have shown a cross-over into humans.
As agencies in the U.S. and across the globe set out countermeasures against the bird flu outbreak, the idea that it could move from being zoonotic to human-to-human are far and few between, yet concerning, particularly since the COVID pandemic and rising mpox cases. As more endeavors are set up to allay these fears, the race for new bird flu vaccines and scaling up production continue.
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