The future of avian flu vaccines

In the United States, bird flu has infected cows in nine states, millions of chickens and, two weeks ago, a second dairy farm worker. There is no indication that the virus has acquired the mutations necessary to transmit from one person to another, but the possibility of a new pandemic has health authorities on high alert. Last week they said they were working on receive 4.8 million vaccines against H5N1 avian influenza as a precautionary measure.

The good news is that We are much more prepared for an outbreak of bird flu than for coronavirus. We know much more about bird flu than we do about coronaviruses, and the country has hundreds of thousands of doses of vaccine stockpiled.

The bad news is that More than 600 million doses would be needed to cover the entire US population., at a rate of two doses per person. And the process typically used to produce flu vaccines takes months and relies on large quantities of chicken eggs. Yes, chickens. One of the birds susceptible to avian influenza.

The idea of ​​growing the influenza virus in fertilized chicken eggs came from Australian virologist Frank McFarlane Burnett. In 1936, he discovered that if he drilled a small hole in the shell of a chicken egg and introduced influenza virus between the shell and the inner membrane, he could cause the virus to multiply.

Even now we continue to grow the influenza virus in much the same way. “I think that a lot has to do with the existing infrastructureSays Scott Hensley, an immunologist at the Perelman School of Medicine at the University of Pennsylvania. Companies find it difficult to change.

Process It works like this: Health authorities provide vaccine manufacturers with a candidate virus that matches circulating influenza strains. This virus is injected into fertilized chicken eggs, where it multiplies for several days. The virus is then collected, removed (in most uses), purified and packaged.

However, making flu vaccine in eggs has several serious drawbacks. First of all, the virus does not always reproduce well in eggs. So the first step in developing a vaccine is to create a virus that does it. This is achieved through an onboarding process that can take weeks or even months. And this is especially difficult in the case of bird flu: viruses like H5N1 are lethal to birds, so they can kill the embryo before the egg can produce the virus.

To prevent this, scientists will have to develop a weakened version of the virus by combining genes from the avian flu virus with genes typically used to make vaccines against the seasonal flu virus.

Secondly, there is a problem get enough chickens and eggs. Currently, numerous egg production lines are focused on the production of seasonal flu vaccines. They could switch to bird flu, but “we don’t have the ability to do both,” Amesh Adalja, an infectious disease specialist at Johns Hopkins University, told KFF Health News. The US government is so concerned about the egg supply that it secretly keeps flocks of chickens scattered across the country under strict guard.

Most influenza virus used in vaccines is grown in eggs, but there are alternatives. The seasonal flu vaccine Flucelvax, produced by CSL Seqirus, is grown on a cell line obtained in the 1950s from cocker spaniel kidneys. The virus used in Protein Sciences’ FluBlok seasonal flu vaccine is not cultured, but synthesized. Scientists create an insect virus that carries the gene for hemagglutinin, a key component of the influenza virus, which causes the human immune system to produce antibodies against it. This modified virus turns insect cells into small plants that produce hemagglutinin.

On the other hand, we have mRNA vaccines, which do not require vaccine manufacturers to grow any viruses. There are no approved mRNA vaccines against influenza yet, but many companies are vigorously working on them, including Pfizer, Moderna, Sanofi and GSK. “With the coronavirus vaccines and the infrastructure in place, we now have the ability to ramp up production of mRNA vaccines very quickly,” Hensley says.

this week Financial Times reported that the US government will soon close an agreement with Moderna to provide tens of millions of dollars to fund large clinical trials of the avian flu vaccine that the company is developing.

Except, There are signs that egg-free vaccines may work better than egg-based vaccines.. A Centers for Disease Control and Prevention study published in January found that people who received Flucelvax or FluBlok had stronger antibody responses than those who received egg-based flu vaccines. The reason is that viruses grown in eggs sometimes acquire mutations that help them grow better in them. These mutations can change the virus so much that the immune response generated by the vaccine will not work as effectively against the actual flu virus circulating in the population.

Hensley and his colleagues are developing an mRNA vaccine against avian influenza. They’ve only tested it on animals so far, but the vaccine has worked well: “All of our preclinical animal studies show that these vaccines produce a much stronger antibody response than regular flu vaccines,” he notes.

No one can predict when we will need a pandemic flu vaccine. However, just because avian flu hasn’t become a pandemic doesn’t mean it won’t happen. “I’m concerned about the livestock situation,” Hensley says. He explains that people come into contact with cows all the time, although so far there have only been a few cases of human illness: “The fear is that one of these exposures could lead to a fire,” he says. Let’s make sure we put it out quickly.

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Read more about file MIT Technology Review

In a previous episode of The Checkup, Jessica Hamzelu explained what it takes for bird flu to spread to humans. And last month, after avian flu spread among cows, I published an update discussing strategies to protect people and animals.

I don’t need to tell you that mRNA vaccines are big business. In 2021 MIT Technology Review highlighted them as one of the 10 most innovative technologies of the year. Antonio Regalado analyzed its enormous potential to transform medicine. Jessica Hamzelu has written about other diseases that researchers hope to tackle. I wrote the article after two mRNA researchers won the Nobel Prize. And earlier this year, I wrote about a new type of mRNA vaccine that is self-multiplying, meaning it not only works at lower doses, but also stays in the body longer.

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