Lessons from the latest pandemic point the way to universal flu vaccines

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Hemagglutinin (HA) is a protein on the surface of the flu virus that binds to receptors on host cells. A new study shows how antibodies targeting stable, conserved portions of HA, shown in the colored portions here, were very effective in fighting the virus. Credit: Guthmiller et al.

A new study from the University of Chicago and the Scripps Research Institute shows that during the last major pandemic — the 2009 H1N1 flu pandemic — people developed strong, effective immune responses to stable, conserved parts of the virus. This suggests a strategy to develop universal flu vaccines designed to generate the same responses, rather than targeting parts of the virus that tend to evolve rapidly and require a new vaccine each year.

The flu is a difficult and frustrating goal for vaccines. There are two main types of influenza viruses that can infect humans, which evolve rapidly from season to season. When seasonal flu vaccines are developed, health officials try to anticipate the predominant variation in the virus that will circulate that year. These predictions are usually slightly off. Sometimes unexpected new variants appear, which means the it may not be very effective. To prevent this, the ultimate goal of many flu researchers is to develop a universal vaccine that can explain any strain or variation of the virus in a given year, or even longer.

The new study, published on June 2 a Scientific translational medicine, was directed by Uchichago immunologists Jenna Guthmiller, Ph.D., and Patrick Wilson, Ph.D., along with structural biologists Julianna Han, Ph.D., and Andrew Ward, Ph.D., of the Scripps Research Institute. They studied the immune responses of people who were first exposed to 2009 H1N1 , either by infection or vaccine.

The researchers saw that these people’s immune systems were reminiscent of their childhood memory B cells that produced widely neutralizing antibodies against highly conserved parts in the head of a protein called hemagglutinin (HA), a protein surface of the virus that binds to the receptors of the host cells. These antibody responses were very effective in combating the virus and, as they targeted conserved parts of the HA protein, i.e., they do not change very often, they could provide an attractive target for a vaccine to generate these same. robust immune responses.

In a separate study from 2020, Guthmiller and colleagues found so-called polyreactive antibodies that can bind to various conserved sites of the flu virus. Now, the new study reveals more details about conditions that may recall the same strong immune responses as this first exposure.

“That’s the most exciting thing about this study,” Guthmilller said. “Not only have we found these antibodies widely neutralizing, but we now know a way to induce them.”

The only problem is that in subsequent encounters with the virus or a vaccine, the body does not generate these same superfluous antibodies. In contrast, for reasons that are unclear, the immune system tends to target new variations in the virus. This may be effective at the time, but it is not very useful when another slightly different version of the flu appears.

“When people come across this virus for the second or third time, their antibody response is almost completely dominated against these more variable parts of the virus, “Guthmiller said.” So this is the uphill battle we continue to face with this. “

The trick to solving this is to design a vaccine that recreates that initial encounter with H1N1, using a version of the HA protein that maintains the conservative and potent components that cause antibodies and replaces the variable parts with other molecules that will not distract. the immune system.

“Structural studies were essential to delineate conserved areas of the HA protein,” said Han, who co-authored the new study and received his doctorate from the Uchicago Microbiology Commission. “Now this data can be used to fine-tune vaccine targets.”

About the last century, two of the four flu pandemics were caused by the H1N1 flu, including the 1918 Spanish flu. which killed up to 100 million people. However, the findings of this study are reassuring in the fight against possible future pandemics caused by other H1 viruses.

“The chances of another pandemic during our lives caused by an H1 it’s pretty high, “Guthmiller said.” Just knowing that we really have the immune tool kit ready to protect us is encouraging. Now it’s just a matter of getting the right vaccine to do it. ”


Details on the widely neutralizing antibodies provide information about the universal flu vaccine


More information:
Jenna J. Guthmiller et al., Early exposure to the H1N1 pandemic virus induced neutralizing antibodies widely targeted at hemagglutinin head epitopes, Scientific translational medicine (2021). DOI: 10.1126 / scitranslmed.abg4535

Citation: Lessons from the latest pandemic point the way to universal flu vaccines (2021, June 4) recovered on June 4, 2021 at https://medicalxpress.com/news/2021-06-lessons- pandemic-universal-flu-vaccines.html

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