Lessons from the last pandemic show the way to a universal flu vaccine

Hemagglutinin (HA) is a protein on the surface of the influenza virus that attaches to receptors on host cells. New studies show how antibodies that target the conserved and stable portion of HA are very effective in fighting the virus. Credits: Guthmiller et al.

During the last outbreak of the 2009 H1N1 influenza pandemic, people have a strong and effective immune response to a stable and conserved portion of the virus, according to a new study from the University of Chicago and the Scripps Research Institute. Developed. This suggests a strategy for developing a universal influenza vaccine designed to produce the same response rather than targeting some of the viruses that are evolving rapidly and require new vaccines each year. ..

Influenza is an elusive and frustrating target for vaccines. There are two main types of influenza virus that infect humans and evolve rapidly from season to season. When developing a seasonal flu vaccine, health authorities try to predict the major variations of the virus that will prevail that year. These predictions are often slightly off. Sometimes new and unexpected variants emerge. vaccine It may not be very effective. To avoid this, the ultimate goal of many influenza researchers is to develop a universal vaccine that can explain a particular year or older virus strain or mutation.

New study published on June 2 Science translational medicineWas led by Dr. Jenna Gasmiller and Dr. Patrick Wilson, immunologists at the University of Chicago, and Dr. Juliana Han and Dr. Andrew Ward, structural biologists at the Scripps Research Institute. They studied the immune response of people who were first exposed to H1N1 in 2009. Pandemic influenza virusFrom either an infection or a vaccine.

Researchers found that the immune system of these people recalled childhood memory B cells and produced a wide range of neutralizing antibodies against a highly conserved portion of a protein called hemagglutinin (HA). Did. These antibody responses were very effective in fighting the virus and targeted the conserved portion of the HA protein (that is, they did not change much), so the vaccine was the same powerful. It may provide an attractive target for generating an immune response.

so Another study in 2020, Guthmiller and colleagues have discovered so-called multi-reactive antibodies that can bind to several conserved sites of the influenza virus. This new study reveals more details about the conditions that evoke the same strong immune response as this initial exposure.

“That’s the interesting part of this study,” said Gasmiller. “Not only have we discovered these broadly neutralizing antibodies, but we also know how to actually induce them.”

The only problem is that the body does not produce similar very effective antibodies when it subsequently encounters a virus or vaccine. Instead, for unknown reasons, the immune system tends to target new mutations in the virus. It may be effective at that time, but it will not be very useful in the future if another, slightly different version of the flu occurs.

“When people encounter the virus two or three times, their antibody response is almost completely dominated. antibody Against the more variable parts of the virus, “Gasmiller said.” This is the difficult battle we are facing, “Gasmiller said.

The trick to avoiding this is to design a vaccine that reproduces the first encounter with H1N1; use a version of the HA protein to retain strong conserved antibody-inducing components and distract the variable. Replace with no other molecule. Immune system.

“Structural studies were essential to reveal the conserved regions of HA proteins,” said Han, co-lead author of the new study and a PhD from the University of Chicago’s Microbiology Commission. .. “These data can now be used to fine-tune vaccine targets.”

In the last century, two of the four pandemics of influenza were caused by the H1N1 influenza, including the 1918 Spanish flu. Pandemic It killed as many as 100 million people. However, the findings of this study provide peace of mind in the fight against future pandemics that may be caused by other H1 viruses.

“The possibility of another pandemic in our lifetime caused by H1 Virus “It’s very expensive,” Gasmiller said. “It’s encouraging just to know that an immune toolkit is actually available to protect ourselves. Now we have the right vaccine to do that. It’s just a matter of doing. ”

More information on antibodies that neutralize extensively provides insights into universal influenza vaccines

For more information:
Initial exposure to the Jenna J. Guthmiller et al. Pandemic H1N1 virus induced a wide range of neutralizing antibodies targeting the head epitope of hemagglutinin. Science translational medicine (2021). DOI: 10.1126 / scitranslmed.abg4535

Quote: The lesson from the last pandemic is the universal influenza vaccine taken from on June 4, 2021. Shows the way to (June 4, 2021)

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Lessons from the last pandemic show the way to a universal flu vaccine

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