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Scientists are getting closer to understanding why some people are immune to the coronavirus, a finding that could help with future vaccine development.

Scientists are getting closer to understanding why some people are immune to the coronavirus, a finding that could help with future vaccine development.

 


Early in the 2021 pandemic, Hugh Potter ate dinner and watched TV next to his wife, who was coughing violently with COVID-19, without even sniffling once.

It's thought that some people avoided COVID-19 because they were careful to avoid infection, or that some people may have been infected but never developed symptoms. Another possibility is that some people have a genetic advantage that makes them highly susceptible to avoiding infection.

“I feel really lucky,” said Potter, 68. “I think just about everyone where I work has it.” Some people were in disbelief that the Pickering, Ontario, resident had managed to avoid infection early in the pandemic.

Now experts studying the genetics of these rare people are making some surprising discoveries.

Last week, scientists Journal Nature Potter found that certain genes were more active in people who weren't infected, and in a complementary research project, he provided DNA from saliva samples to researchers at McGill University Health Centre who are searching for people with golden armour against the virus.

Researchers hope that a better understanding of the early immune response will help them develop a nasal spray version of a coronavirus vaccine, similar to the existing FluMist for preventing flu.

A scientist prepares to administer a low dose of SARS-CoV-2 into the nose of a reclining human volunteer.
Christopher Chiu monitored volunteers' immune responses from the moment a person first encountered SARS-CoV-2, throughout infection, and up until the point when the virus appeared to have been cleared. (Thomas Angus/Imperial College London)

While people may want to forget about the pandemic emergency, The virus is still among us Canada is seeing roughly 20 deaths per week. who More than 2,600 new deaths were reported in April, bringing the total number of confirmed infections to more than 775 million, of which more than 7 million have died worldwide.

Spontaneous infection

To gain insight into why people become ultra-avoidants, in March 2021 researchers in the UK COVID-19 Human Challenge Study gave 36 healthy adult volunteers a low dose of a prototype SARS-CoV-2 via the nose and closely tracked how long it took for their immune cells to become activated. None of the subjects had previously been infected with the virus or vaccinated against it.

The 16 participants, who underwent detailed blood and nasal monitoring, were split into three groups.

  • Six people developed persistent infections and became ill.
  • Three people were infected but quickly cleared the virus.
  • The seven people were found to have successfully prevented infection as they never tested positive in the gold standard PCR tests.

Christopher Chiu, a professor of infectious diseases at Imperial College London, and his co-authors found high levels of activity of a gene called HLA-DQA2, which they believe helps alert the immune system to invaders and destroy the virus quickly.

For medical researchers, this study offers an opportunity to step by step look at what happens in the immune response to the virus and its interactions in both the nose and blood.

Location, location, location

Immunologists not involved in the British study say it's unclear why or how that particular gene confers a protective effect.

“If you asked me to bet on a gene that was associated with prevention, I wouldn't pick that gene,” said Professor Dawn Bowdish, who holds the Canada Research Chair in Ageing and Immunity at McMaster University in Hamilton.

Bowdish said the real estate agent's motto “location, location, location” applies because our noses, blood and lungs each mount different types and timing of immune responses.

A man demonstrates how to use an inhaled vaccine system in a laboratory.
Researcher Michael D'Agostino demonstrates the use of an inhaled vaccine system that aims to block infection altogether. (Georgia Kirkos/McMaster)

For example, a vaccine that is given in the arm is designed to trigger a response from the immune system as part of acquired immunity.

The HLA genes receive the trigger and present it to the fighting cells of the immune system.

Dr. Lynora Saxinger, an infectious disease specialist at the University of Alberta, said that while the particular HLA found in the study was better at blocking COVID infection, it's not necessarily better overall because it's also associated with some diseases such as lupus and rheumatoid arthritis.

Saxinger said that in the study, people with persistent infections were slow to have their immune systems focus on areas inside the nose and nasal mucosa. In contrast, findings from those who mounted the quickest immune responses could galvanize the field of nasal vaccines.

Preventing infection

Research Team McMaster And that University of Ottawa Some researchers are aiming to design a nasal spray or inhaled vaccine to block infection altogether, rather than just prevent the risk of severe illness requiring hospitalization or death from COVID-19, as current vaccines do.

Bowdish said scientists previously thought that activating immune cells in the nose was enough to kill the virus, but a new study from the UK says that cells that drive immune responses in the mouth, nose and lungs are all important.

“As we hope to move into a world where we have inhaled vaccines and nasal vaccines, this gives us some clues about the specific immune genes we want to activate in those vaccines to protect us,” Bowdish said.

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The opportunity to stop transmission is “enormous,” Saxinger said, adding that understanding how to eliminate the virus early is also important to prevent asymptomatic spread.

The pandemic landscape, with variants and vaccine immunity, is very different from when study volunteers were infected: Some people are getting COVID-19 repeatedly as variants have evolved to evade immune defenses, and doctors say COVID-19 symptoms continue to push some older, more vulnerable people hospitalized to the brink.

Next, the British researchers plan to test several potential nasal spray vaccines against the coronavirus family, which includes SARS-CoV-2, MERS and four seasonal cold viruses. Other human challenge studies.

“There may be common characteristics that allow us to consider preventative or early treatment,” Saxinger said.

Sources

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2/ https://www.cbc.ca/news/health/never-covid-1.7248039

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