Scientists are getting closer to making a general flu vaccine

On November 19, 2019, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, described the new research he had in mind to Kim Tingley, author of a leading article in the New York Times. He said at the time that one of the hot topics was the development of a general flu vaccine.

Fauci meant a vaccine that is suitable for all ages and is at least 75% effective against influenza A viruses for a year or more. Influenza A is one of the influenza viruses that causes globalization; But along with influenza B, it also infects up to one billion people worldwide each year, killing some 290,000 to 650,000.

Serious efforts to develop a general flu vaccine began about a decade ago and are accelerating. “Fauci says about this:

This is something I spend a lot of time on. Many scientists are trying to achieve this. It was somewhat embarrassing that a new and updated flu vaccine had to be developed every year. We need to work harder to get a better vaccine that covers all possible versions of the flu.

Last month, after two years and a half of coronavirus infection, I asked Fauci if he guessed in late 2019 that some kind of flu virus could cause the next outbreak. He said:

Of course, they said, what is your worst nightmare? And I was saying, the emergence of a whole new virus that could have jumped from an animal to a human and been transmitted by air, and most likely it would be the flu. The next case may be something like this.

New influenza viruses, transmitted from birds or pigs to humans, have caused globalization in just over a century. It is estimated that about 50 million people were killed during the 1918 globalization. When a large number of the world’s population gained some immunity from infection or vaccination against those viruses, the viruses became extinct or seasonal. (Many believe that SARS-CoV-2 will eventually become endemic and, like the coronavirus that causes colds, will be circulating in the lower echelons of society).

The reason why it is impossible to eradicate the flu virus has something to do with its structure. The surface of all strains of influenza is covered with protein bumps, the most important of which are hemagglutinin (HA) and neuraminidase (NA) influenza A and B viruses. (Names of viral strains such as H1N1 describe their various compounds.)

HA proteins have thin, round stems like lollipops. The head part is the part of the protein that attaches to our cells, while the stem contains the means by which cell membranes and viruses integrate, through which the transfer of genetic material takes place.

The HA head is usually the structure that our immune system (alone or with the help of a vaccine) detects as invasive and produces neutralizing antibodies to it; But while viruses such as measles are relatively stable, the genes of influenza viruses are frequently mutated. This causes the shape of the HA head to change constantly; Therefore, vaccines should be changed regularly. (Rarely, an animal flu virus that has HA or a new HA-NA compound acquires the ability to infect humans and cause globalization).

The process of producing and distributing the new vaccine takes about six months, although during this time the circulating strains may deform again. The US Centers for Disease Control and Prevention estimates that vaccines are up to 60 percent effective in preventing the disease if they match seasonal viruses; But when this does not match, their effectiveness is reduced by as much as 10 percent.

Vaccine painting

For almost half a century (the annual influenza vaccination began in 1960), there was no better way to make flu vaccines in the eyes of scientists. Then, around 2008, several research groups discovered an amazing phenomenon in human blood samples: antibodies that could defend against two subtypes of HA.

“The H1 antibodies detected the H5 bird flu and surprised everyone,” said James Crowe, director of the Vanderbilt Vaccine Center. It was found that those antibodies bind to the HA protein stem, not the head. Also, between the HA-NA strains, the stem appeared to mutate relatively less to the head.

“It started the general flu vaccine revolution,” Crow said. We thought the level of the flu virus was infinitely variable; “But in reality, there are parts that rarely change drastically.”

Several groups of researchers are now testing general vaccines at various stages of clinical trials. Some of them, including researchers from the National Institutes of Health, are testing vaccine safety on people during the current flu season. These vaccines produce more stem antibodies than conventional vaccines.

Even if the vaccine is widely effective against different strains of the flu, it is not clear how long this protection will last. (A vaccine that only lasts two or three years will have a huge public health benefit.)

There is evidence that the immune system can provide lifelong defense against the flu, but there is a problem. According to Aubrey Gordon, an associate professor of epidemiology at the University of Michigan School of Public Health, people seem to be labeled with the HA proteins they encountered as children. Individuals’ responses to viruses and influenza vaccines vary based on their previous exposure. “It doesn’t just matter what you’ve been up to recently,” he says. “Rather, your first encounters are crucial in determining the immune system’s response for the rest of your life.”

Individuals labeled with one of the HA subtypes have a ready response to similar viruses. But when they become infected with a virus that is less similar to past viruses, they may still develop antibodies that are somewhat compatible with the previous virus strain, reducing their effectiveness.

An article published in the journal Science in 2016 showed that the year of birth of a person, more than their age, determines the risk of developing a serious illness caused by the influenza virus. For example, the 1918 birth was disproportionately fatal to young people; Probably because the hemagglutinin proteins of the new virus were different from the hemagglutinin proteins of the circulating influenza viruses in their childhood. The same group performed much better during the 1968 globalization, due to a virus that was probably more consistent with their initial exposure.

How the label works still remains unclear, but according to Fauci, discovering it will likely be the key to achieving public flu vaccines. He says there are still many unknowns.

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The success of Covid vaccines has led many of us to believe that vaccines are relatively easy to make for any infectious disease. “Florian Kramer, a virologist at Aikan Medical School in Montessay, says:

I think SARS-CoV-2 has raised our expectations. Normally, it takes several years to make a vaccine. In addition, having effective vaccines can prevent efforts to make better vaccines.

In the face of a new virus that spreads rapidly among the population during globalization, researchers can vaccinate one group of placebo and another group and see results quickly. But many find it immoral to ask people not to get a proven flu vaccine so they can act as a control group.

To see if a new flu vaccine effectively covers several recurrences of the flu, researchers must vaccinate many people with a new vaccine or an existing flu vaccine for several seasons and then wait for a year in which the seasonal vaccine works poorly and the vaccine The experiment works well.

In addition, clinical trials are expensive. The corona virus has shown how urgent globalization can help conduct tests by gathering and directing all available resources, but it has also taken virologists time and resources away from the flu.

“If Operation Warp Speed ​​existed for general influenza vaccines, we might now have one of these vaccines,” Kramer said. Under the current circumstances, Fauci hopes that one of the candidates on trial will be able to prepare within the next five years.

Michael Osterholm, director of the Center for Infectious Diseases Research and Policy at the University of Minnesota, says the emergence of the coronavirus omicron virus is a sign that a general vaccine should be given to Covid 19 as well. In fact, research on such a vaccine is underway. But according to Osterholm:

The potential threat posed by omicrons should also be a wake-up call to the world as to why these vaccines are so important. In any case, more flu pandemics are on the way, and we do not want to wake up one morning saying that we wish we had worked harder to make a flu shot.

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