Potent, broadly-protective flu vaccines to protect against potential pandemic influenza viruses such as H5N1
PopVax’s influenza vaccine designs elicit as much as 250x greater antibody titer against seasonal strains than existing approved flu vaccines, as well as robust antibody titer against H5N1
As we ring in the New Year, amidst the din of the music and fireworks, we would be remiss not to strain to hear the soft ticking of a potential time bomb that is at once new and, for those of us who tracked the emergence of COVID-19, depressingly familiar.
Hundreds of herds of cows in the United States, including 70% of all dairy cow herds in California, have been infected with H5N1 influenza. As Alex Tabarrok notes in his recent piece,1 the massive impact of the infection on the health of these cows has been somewhat overlooked. He quotes a FarmProgress piece reporting on a 500-cow farm in Michigan:2
“The cows were lethargic and didn’t move. Water consumption dropped from 40 gallons to 5 gallons a day.”
Farmers have gone to extraordinary lengths to treat the sick cows:3
“In 14-hour shifts, dairy workers pumped gallons of electrolyte-rich fluids into ailing cows through metal tubes inserted into the esophagus… It was like watching a field hospital on an active battlefront treating hundreds of wounded soldiers.”
The spread of the virus has also led to over 100 million chickens, turkeys, and ducks being culled. There have been 66 confirmed human cases in the U.S. in the past year, and at least one infected teenager in Canada was hospitalized and remained in critical condition for weeks. In that case, and the case of an individual in Louisiana who also became critically ill, sequencing revealed mutations in the virus that are suspected to have occurred during human infection which may make it easier for the virus to infect the upper airways and transmit from an infected host to others.4
While there has been no sustained human-to-human transmission so far, that could change very quickly if the virus is given more opportunities to mutate inside human hosts — a recent paper analyzing antigen structure and binding in the journal Science posits that bovine H5N1 is only one key mutation away from preferentially infecting human cells.5
This might all amount to nothing — the bomb may be a dud, which is certainly what I’m hoping for. Or, on the other extreme of the spectrum of outcomes, this might metaphorically blow up in our collective faces, and literally claim millions of lives if a human-transmissible and highly-pathogenic version of H5N1 begins to circulate widely across the globe.
Existing seasonal influenza vaccines do not generally elicit immune responses against H5N1, and most people have not been exposed to H5N1, so the general population is likely completely unprotected. While there are H5N1-specific vaccines that have been approved in the US and other countries, they are not generally available to the public, and in any case have not yet been updated to match the key currently-circulating strains of concern.
Influenza is a very tricky virus. It has the potential to mutate even faster than SARS-CoV-2, and the current paradigm of strain-specific vaccines which offer narrow protection may result in vaccines that are always many steps behind the virus.
What we need are broadly-protective vaccines — vaccines that can provide coverage of current and even future potential strains of H5N1, and indeed other key strains of influenza that threaten us now or may threaten us in the future. Vaccines of this kind would reduce the need to constantly update strains in response to mutations in the virus, and are thus more likely to be efficacious in a fast-evolving pandemic scenario. These kinds of broadly-protective vaccines require specialized design to elicit an immune response that is broadly functional across multiple strains and mutated versions of strains.
At PopVax, we have been advancing the frontier of this kind of vaccine design, starting with our COVID-19 vaccine, which has been selected for inclusion in the U.S. government’s Project NextGen. NIAID, part of the U.S. NIH, will conduct and sponsor a first-in-human trial of this candidate in the U.S. in 2025.6
We’ve now developed a variety of influenza vaccines intended to be broadly protective, and have two candidates that are already showing early signs of utility against H5N1. The first is our seasonal influenza candidate which, despite not containing an H5N1 antigen, elicits a potent antibody response against H5N1 just 21 days after a single dose in mice, in contrast with existing licensed seasonal influenza vaccines approved in the U.S. & Europe, which elicit H5N1-specific antibody responses that are barely distinguishable from the control. Our vaccine candidate also elicits as much as 250x greater antibody response in mice against seasonal strains compared with a seasonal influenza vaccine from the global market leader. A vaccine such as ours could be used primarily as a seasonal influenza vaccine of the kind that hundreds of millions of people take each year, but has the potential to additionally provide some protection against H5N1 and other emerging strains which current influenza vaccines do not.
We also have an H5N1 influenza vaccine candidate that elicits robust antibody responses against both the same strain of H5N1 that it is based on as well as other distinct H5N1 strains in mice.
We can also combine this vaccine with our seasonal influenza vaccine discussed above to increase coverage of both H5N1 strains that are currently circulating and future strains that may emerge as the virus mutates. We believe we can initiate clinical trials for versions of these vaccines this year and, if they are found to be safe as well as robustly and broadly immunogenic in humans, work with regulators to proceed rapidly towards licensure if the situation demands.
We are in the process of using the technology behind these vaccines to develop a broadly-protective influenza vaccine that covers all key seasonal and potential pandemic strains of flu, with the intention of pre-empting and preventing the emergence of new strains altogether. We are eager to work with investors, industry partners, governments, and regulators to accelerate the development and clinical testing of our influenza vaccines.
I invite interested collaborators and funders to reach out over email at flu25@popvax.com. I will be in San Francisco along with senior colleagues from January 13th to 20th during the JP Morgan Healthcare Conference, and would be delighted to meet with interested folks in person there as well.
Soham Sankaran,
Founder & CEO,
PopVax.
PopVax is a Gates Foundation & Vitalik Buterin-funded Indian full-stack biotech harnessing the power of mRNA and machine learning-enabled computational protein design to develop broadly-protective vaccines.
We are now 70+ people across our computational, experimental, analytical, process development, quality, and regulatory teams at the PopVax RNA Foundry, our integrated R&D and process development facility in Hyderabad. We have six novel vaccine candidates in our preclinical pipeline, and intend to initiate five clinical trials over the next two years. We’re actively hiring across all of those teams to support our new programs, so if you’re interested in working with us, take a look at our open job opportunities at jobs.popvax.com.
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