Can you kill the flu in one shot?

In 2009, global health authorities began tracking a new type of influenza. It first appeared in Mexico in March and soon infected thousands. The flu tends to kill very young people and very old people, but this flu was different. Other than that, it seemed to have a serious impact on healthy young adults.

American epidemiologists soon learned of cases in California, Texas, and Kansas. By the end of April, the virus had reached high school in Queens, and several children returning from their trip to Mexico had infected one-third of their students’ bodies. The Mexican government closed schools, banned large rallies, and the United States considered the same. “It was a very scary situation,” Richard Besser, then deputy director of the Centers for Disease Control and Prevention, told me. The initial estimate is “Swine fluAs new strains became known, 14% of infected strains died. This is more than 200 times more lethal than the typical seasonal flu. The virus quickly spread to more than 150 countries, and the Obama administration considered delaying the start of school after Thanksgiving until a second wave could develop. Manufacturers were worried about the supply of vaccines. Like most flu vaccines, swine flu vaccines were raised on eggs. “If you yell at them, they won’t grow fast,” Tom Frieden, who succeeded Besser as CDC director, said at a news conference.

In the end, the world was lucky. Early statistics were misleading. Swine flu was highly contagious, but not particularly fatal. The reverse is also true. bird-fluSpread around the world in the winter of 2005-06, it is not particularly contagious, but it is extremely deadly and kills more than half of infected people. Each influenza virus has its own epidemiological profile, which is determined by its genetic composition, and the influenza gene changes each year. Howard Markel, an epidemic doctor and historian, said in early 2000, “Flatten the curveCompared the exchangeable genetic component of influenza with “two-wheeled luck.” Double pain (combination of spreadability and lethality) COVID-19, or 1918 influenzaIt looks like a 24-hour bug that killed 40 to 100 million people.

After the relatively harmless nature of swine flu was revealed Many asked If the alert it caused was justified. A Swiss study found that confidence in financial institutions was declining. Some scientists and officials said World Health Organization Stir up a “fake” pandemic to justify your budget. However, most people have drawn the opposite conclusion from their experience. They became even more worried when trying to prepare for the deadly flu epidemic. “There was an overwhelming sense of relief,” Besser said. “If this was like 1918, we were certainly not ready.”

In fact, we can never be completely prepared for the flu. We know it will comeStill, like the first autumn leaves, three times in the last century, in 1918, 1957, and 1968, it flattened us and killed more than a million people each time. Even in normal years, the disease affects one billion people worldwide and kills hundreds of thousands. One study estimates that the US economy will cost nearly $ 100 billion annually. Our primary weapon against the virus, the flu vaccine, is terribly inadequate. Over the last decade and a half in the United States, influenza vaccines have a 40% chance of preventing illness. Especially in bad years, when the vaccine was not well tuned to circulating strains, they had only 10 percent protection. Today, the coronavirus pandemic is, of course, the subject of our most energetic efforts.Still, in the 2009 article, as infectious disease experts David Morens, Jeffrey Taubenberger, and Anthony Fauci wrote. New England Journal of Medicine, “We live in a pandemic era that began around 1918,” when the flu used the transport network to cross the world. Since the 1918 pandemic, this century-long multi-wave pandemic has killed about the same number of people.

Chickenpox, diphtheria, measles, Mumps, Polio, Rabies, rubella, smallpox, tetanus, typhoid fever, whooping cough, yellow fever-and to some extent we added COVIDAdd -19 to the list. However, the pathogens behind these illnesses tend to be relatively static compared to the flu, which recurs in a troublesome way each year. Scientists have dreamed of what is called a “universal” flu vaccine for decades. It can target many strains of the virus. Universal vaccines will save countless lives every year, not just this year. Taken together, these numbers will be one of the greatest medical advances in history. Until recently, it was beyond the scope of molecular biology. But new technologies are expanding our capabilities, and researchers are learning how to spot influenza disguise. Without knowing it, we live at the forefront of amazing scientific achievements. One of the longest pandemics in the world is likely to end soon.

What we call “flu” is actually the plural. Several strains circulate every season. In the summer in one hemisphere, influenza infections surge in the other hemisphere. WHO virologists investigate the virus and share what they have learned with pharmaceutical companies. Later, pharmaceutical researchers often develop tetravalent vaccines that simultaneously target four separate strains. It’s a shotgun approach.

It takes more than 6 months to design, test and manufacture a season’s flu vaccine. At that time, many things can change. Outside the world, stocks change and quarrel for dominance. The epidemic varieties will disappear and the sleeping people will come to the fore. Arnold Monto, an epidemiologist at the University of Michigan who advised the Food and Drug Administration on targeting influenza vaccines, told me that “science and a little art” was needed to select the strains to target. The selected influenza virus will further mutate as a result of vaccine production. By the time the needle reaches the arm, the vaccine may be off-target or outdated.

Each strain of influenza can also be seen as a plural. Morrens, Taubenberger, and Fauci explain that “it helps to think of the influenza virus as a” genetic team “of eight members, rather than as a separate entity.” The flu virus writes, “You may have to trade off one or more team members to give way to a new genetic” player “with unique skills.”

The surface of the virus is covered with a forest of proteins. When a virus’s gene changes, so does the protein. From a vaccine perspective, two proteins are very important. The first hemagglutinin (HA) helps the virus invade cells. The second neuraminidase (NA) helps you get out of them. The mysterious codenames given to the influenza virus (H1N1, H3N2, etc.) reflect the dozens of numbered variations that contain these proteins. When the virus is replicated, the variation itself changes, making vaccine targeting even more difficult. Influenza vaccines focus on the more vulnerable HA proteins and need to be adjusted for the latest version of the virus.

Some viruses are siled within a single species. However, influenza easily migrates between several species, which adds to its recombination range. “There are hundreds of warm-blooded animals that are routinely infected with the influenza virus,” said Taubemberger, who is responsible for the pathogenesis and evolution section of the virus. NIAID, Said to me. “You can move from birds to horses, pigs, and humans.” If a bird is infected with two flu strains at once, those strains can combine to create a new virus. The virus, in turn, can invade another animal. In 1918, H1N1 infected humans and pigs. Swine flu, which surprised epidemiologists in 2009, emerged when the two pig strains converged and then returned to humans. The existence of so-called animal depots for influenza increases the likelihood that virologists will face radically changed enemies at any given year. It also means that it is almost impossible to achieve herd immunity. “Smallpox, measles, polio, and other viruses that are specifically adapted to humans … Vaccination of enough people to generate herd immunity can actually eliminate the virus,” Tau said. Bemberger said. “But the flu is inhabited by hundreds of species of animals and is constantly moving around, so we can’t get rid of it. Therefore, we need a better strategy.”

The vaccine contains an antigen. It is a complex molecule that stimulates the immune system to produce effective antibodies. In some cases, an antigen is a synthetic molecule designed to mimic some of the target viruses. In other cases, they are actually the actual part of the censored virus.Antigen COVIDThe -19 vaccine is a version of the spiked protein. SARS-CoV-2 is used to enter our cells. The HA protein that corresponds to the flu looks like a mushroom. Since 19-40, we have been producing influenza vaccines in much the same way. Researchers divide the virus using chemicals that propagate the virus in eggs and inactivate the virus, but leave the mushroom protein intact. Unfortunately, when our immune system builds antibodies in response to these proteins, they tend to target mushroom caps, where the most variable elements are present. Researchers still do not understand why our antibodies are targeting the most variable parts of our enemies. But that is not the best result. More effective antibodies attach to the less variable stem and nullify it.

Börries Brandenburg, Science Director of Janssen Vaccines, part of Johnson & Johnson, told me how the company tackled the cap issue. Take your head off with a French solution. Presents the immune system with headless molecules. Creating capless mushrooms (what Janssen researchers call “mini HA”) is harder than you think. Proteins such as HA are actually a combination of hundreds of small molecules called amino acids. These acids, like the pearls of a necklace, appear linked in sequence from our intracellular factories. Eventually, the necklace twists and curls on its own, Form a 3D shape.. Therefore, mushrooms cannot be sliced ​​and diced. If you decapitate it, the pearl will roll. Protein designers who break loops need to find a way to close the loop. When we spoke, the background of Brandenburg’s video chat was Escher’s illustration of the stairs going in all directions. When the call was over, I commented that the recursive pathway behind him was reminiscent of a loop chain of amino acids. He saw them differently: “This shows how the study goes,” he said.