Generation Xers are permanently susceptible to H3N2 influenza strains

It may be difficult to get someone to think about infectious diseases other than COVID-19 these days, but the flu epidemic is approaching and could exacerbate the current global pandemic. Currently, to add a more complex level to human viral infections, researchers at the University of Pennsylvania (UPenn) Perelman Medical College have found that middle-aged individuals (those born in the late 1960s and 1970s) are those. The antibody binds to the H3N2 virus but cannot prevent infection, so it remains permanently susceptible to the H3N2 influenza virus.

Most humans are infected with the influenza virus by the age of 3-4 years. These early childhood infections can elicit a strong, long-term memory-immune response. The H3N2 influenza virus began to spread to humans in 1968 and has evolved significantly over the last 51 years. Therefore, the year of birth of an individual largely predicts a particular type of H3N2 virus that was first encountered in childhood.

“We found that older individuals have different specificities for H3N2 influenza virus antibodies,” explained Scott Hensley, an associate professor of microbiology at Penn Medicine. “Our study shows that childhood infections can leave lifelong immunological imprints and affect how individuals subsequently respond to antigenically different viral strains.”

The results of the new study were recently published Natural communication “Middle-aged individuals may be in a permanent state of H3N2 influenza virus susceptibility.. “

In the current study, UPenn researchers collected from 140 children (1 to 17 years old) and 212 adults (18 to 90 years old) during the summer months 2017 to 2018. A serological study was completed using a serum sample. They first measured differences in antibody reactivity to different strains of H3N2, and then measured neutralizing and non-neutralizing antibodies.

“We have completed a large serological study to elucidate the specificity of antibodies against the modern H3N2 virus in individuals of different ages who are likely to have been primed with different H3N2 strains in childhood. The authors write. “Most humans who were first infected with the H3N2 virus strains of the 1960s and 1970s in childhood were found to have non-neutralizing antibodies against the modern 3c2.A H3N2 virus.”

Neutralizing antibodies can prevent viral infections, but non-neutralizing antibodies are only effective after an infection has occurred. The researchers found that samples from children aged 3 to 10 years had the highest levels of neutralizing antibodies against the modern H3N2 virus, but most middle-aged samples had antibodies that could bind to these viruses. I have, but these antibodies couldn’t prevent the virus infection.

Hensley said his team’s findings were in line with the concept known as “Original Antigenicity” (OAS), first proposed by Tom Francis Jr. in 1960. It is very different compared to the modern H3N2 virus. When infected with the recent H3N2 virus, these individuals tend to produce antibodies against the region conserved in the older H3N2 strain, and these types of antibodies usually do not prevent viral infection. “

According to the research team, the presence of high levels of non-neutralizing antibodies in middle-aged adults may contribute to the sustained persistence of the H3N2 virus in the human population. Their findings may also be associated with an abnormal age distribution of H3N2 infections during the 2017-2018 season, with H3N2 activity in middle-aged and older adults peaking earlier than in children and young adults. Reached.

Researchers say it is important to continuously complete large-scale serological studies in a variety of older people, including donors from populations with different vaccination rates. A better understanding of immunity within populations and individuals may lead to improved models that better predict the evolutionary trajectory of different influenza virus strains.

“Large-scale serological studies reveal why the effectiveness of influenza vaccines varies among individuals with different immune histories, while at the same time designing better vaccines that can elicit a protective response in all age groups. Identify the barriers that need to be overcome. ”Concluded Dr. Sigrid Gouma, Principal Investigator, Ph.D. in Microbiology at UPenn.