What if the first flu infection shapes our immunity against future airborne viruses, including SARS-CoV-2? This is the theory by researchers at the University of Pittsburgh, who however point out that not all flu strains trigger the same initial immune defense.
- By conducting an experiment on ferrets, the researchers found that those exposed to the H1N1 virus were subsequently immune to the H3N2 virus. The converse, however, is not true.
- This therefore suggests that the first infection with a virus or “antigenic original sin” determines how our organism will react to future viruses.
- This discovery explains in particular why certain categories of the population develop more severe forms of Covid-19, while others have only a mild form of the disease.
In everyone’s immune history, the first infection with the flu virus is paramount, as it shapes how we respond to future airborne flu viruses, including emerging pandemic strains such as SARS-CoV-2.
This is what virologists from the University of Pittsburgh School of Medicine (United States) argue in a study published in the journal PLOS Pathogens. According to them, the first influenza infection could explain the different levels of severity and susceptibility to Covid-19.
“Having the flu once does not make you immune to all future flu viruses, explains Seema Lakdawala, assistant professor of microbiology and molecular genetics, and lead author of the study. Having had the SARS virus in 2003 or one of the circulating cold coronaviruses does not necessarily mean that you cannot be infected with SARS-CoV-2. But your susceptibility to infection may be different from that of someone who has never encountered coronavirus.”
In search of antigenic original sin
To analyze the immune response to influenza, the researchers used ferrets, which have a similar susceptibility to humans. The experiment was designed to test the concept of “original antigenic sin”, i.e. when a person’s first exposure to a pathogen marks their immunity to all future infections.
This phenomenon has been observed in populations affected by previous influenza epidemics and pandemics. For example, the 2009 H1N1 flu pandemic disproportionately affected people between the ages of 5 and 24, suggesting that older people were exposed to an earlier flu strain that gave them long-lasting immunity, thus protecting against the new strain.
In the ferret experiment, scientists infected different groups of ferrets that had never had the flu with one of two different strains of flu – seasonal H3N2 flu or the 2009 pandemic H1N1 flu – and waited three months to allow the immune system to develop more mature immunity against the strain to which they have been exposed.
Then the ferrets immunized against the H3N2 strain were exposed to ferrets contagious to the H1N1 virus, and the ferrets immunized against the H1N1 strain were exposed to ferrets contagious to the H3N2 virus.
The researchers mixed the contagious ferrets with their peers for 8 hours a day over a 5-day period, to mimic human workdays, or continuously for 2 days, such as on a family weekend.
An adaptive immune response
The results showed that ferrets previously infected with the H1N1 virus were protected against airborne transmission of H3N2 influenza from another contagious ferret. But ferrets that had already been infected with the H3N2 virus did not have the same level of protection against the H1N1 flu and were infected at the same rate as an animal without prior immunity.
“It was really surprising”believes Professor Lakdawala, who believes that “our immunity may determine our susceptibility to subsequent infections, but it is not uniform”.
While the experiment did not reveal why ferrets previously infected with the H1N1 virus were protected against H3N2, or why prior H3N2 infection did not block the H1N1 virus, the scientists did find that immunity was not due to neutralizing antibodies. These antibodies are acquired following vaccination or infection that specifically target and neutralize a defined pathogen. This finding indicates that the immunity was probably due to the adaptive immune response: this means that the previous infection with the H1N1 virus caused the immune system to be on the lookout for H3N2 and eliminate it quickly.
This work needs to be completed to better understand the immunological mechanism, but could now make it possible to understand how infections, in particular Covid-19, affect people according to their previous exposure, and thus develop more targeted interventions.
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