Middle-aged individuals may be in a permanent state of susceptibility to the H3N2 flu virus


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Penn Medicine researchers have found that middle-aged individuals – born in the late 1960s and 1970s – may be in a permanent state of susceptibility to H3N2 influenza virus because their antibodies bind to the H3N2 virus but According to a new study, fail to prevent infection. Under the leadership of Scott Hensley, an Associate Professor of Microbiology at the Perelman School of Medicine at the University of Pennsylvania, Ph.D. The paper was published today Nature communication.

“We found that different older individuals have different H3N2 flu virus antibody specificities,” Hensley said. “Our study suggests that early childhood infections can leave lifelong immunological impressions that affect how individuals react to different viral strains later in life.”

Most humans are infected with influenza virus from three to four years of age, and these early childhood infections can affect the strong, long-lasting memory immune response. The H3N2 influenza virus began circulating in humans in 1968 and has evolved considerably over the last 51 years. Therefore, a person’s birth year largely predicts which specific type of H3N2 virus they got in childhood.

Researchers completed a serological survey — a blood test that measures antibody levels — using 140 samples (ages 17 to 17) and 212 adults (18) using serum samples collected in the summer months before the 2017-2018 season. Age of 90). They first measured differences in antibody response in different strains of H3N2, and were then measured for neutral and non-neutralizing antibodies. Neutral antibodies can prevent viral infections, while non-neutral antibodies can help only after infection. Samples from children aged three to ten had the highest levels of neutralizing antibodies against the contemporary H3N2 virus, while most middle-aged samples had antibodies that could bind to these viruses but these antibodies were viral infections. Could not stop

Hensley said his team’s findings are consistent with a concept known as the “original antigen sin” (OAS), originally proposed by Tom Francis, Jr. in 1960. “Most individuals born in the late 1960s and 1970s were immunologically immunized with the H3N2 virus, which is very different from the contemporary H3N2 virus. After the recent H3N2 virus infection, these individuals are older H3N2. The strains produce antibodies against protected areas and these types of antibodies usually do not prevent viral infection. ”

According to the research team, it is possible that the presence of high levels of non-neutralizing antibodies in middle-aged adults may have contributed to the persistence of H3N2 virus in human populations. Their findings may be related to the abnormal age distribution of H3N2 infections during the 2017–2018 season, with H3N2 activity occurring earlier in middle-aged and older adults than in children and young adults.

Researchers say that it will be important to consistently complete large serological surveys in various older individuals, including donors from populations with different vaccination rates. A better understanding of immunity within populations and within individuals will likely lead to better models that are better at estimating evolutionary estimates of various influenza virus strains.

“Large serological studies may shed light on why the effectiveness of flu vaccines varies among individuals with different immune histories, while designing better vaccines also requires identifying barriers to overcome. Are able to elicit protective responses in all age groups, ”Sigrid Gouma, PhD, a postdoctoral researcher of microbiology and the first author on the paper.


Influenza-neutralizing antibodies produced in human subjects are given experimental vaccines


more information:
Sigrid Gouma et al, Middle-aged individuals may be in a permanent state of susceptibility to H3N2 influenza virus, Nature communication (2020). DOI: 10.1038 / s41467-020-18465-x

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