Influenza 2020/2021: Pennsylvania Study Shows Those Born In Late 1960s And In 1970s May Be In A Perpetual State Of H3N2 Flu Virus Susceptibility
: Researchers from the Perelman School of Medicine- University of Pennsylvania have found that middle-aged individuals ie those born in the late 1960s and the 1970s may be in a perpetual state of H3N2 influenza virus susceptibility because their antibodies bind to H3N2 viruses but fail to prevent infections.
The study findings were published in the journal: Nature Communications. https://www.nature.com/articles/s41467-020-18465-x
Dr Scott Hensley, Ph.D., an associate professor of Microbiology at the Perelman School of Medicine at the University of Pennsylvania told Thailand Medical News, "Our study team found that different aged individuals have different H3N2 flu virus antibody specificities. Our research shows that early childhood infections can leave lifelong immunological imprints that affect how individuals respond to antigenically distinct viral strains later in life."
Typically most humans are infected with influenza viruses by three to four years of age, and these initial childhood infections can elicit strong, long lasting memory immune responses.
The H3N2 influenza viruses began circulating in humans in 1968 and have evolved substantially over the past 51 years. Therefore, an individual's birth year largely predicts which specific type of H3N2 virus they first encountered in childhood.
The study team completed a serological survey ie a blood test that measures antibody levels using serum samples collected in the summer months prior to the 2017-2018 season from 140 children (ages one to 17) and 212 adults (ages 18 to 90).
The team first measured the differences in antibody reactivity to various strains of H3N2, and then measured for neutralizing and non-neutralizing antibodies. Neutralizing antibodies can prevent viral infections, whereas non-neutralizing antibodies can only help after an infection takes place. Samples from children aged three to ten years old had the highest levels of neutralizing antibodies against contemporary H3N2 viruses, while most middle-aged samples had antibodies that could bind to these viruses but these antibodies could not prevent viral infections.
The study teams’ findings are consistent with a concept known as "original antigenic sin" (OAS), originally proposed by Dr Tom Francis, Jr. in 1960.
That hypothesis said that "Most individuals born in the late 1960s and 1970s were immunologically imprinted with H3N2 viruses that are very different compared to contemporary H3N2 viruses. Upon infection with recent H3N2 viruses, these individuals tend to produce antibodies against regions that are conserved with older H3N2 strains and these types of antibodies typically do not prevent viral infections."
The study team says that it is possible that the presence of high levels of non-neutralizing antibodies in middle-aged adults has contributed to the continued persistence of H3N2 viruses in the human population. Their findings might also relate to the unusual age distribution of H3N2 infections during the 2017-2018 season, in which H3N2 activity in middle-aged and older adults peaked earlier
compared to children and young adults.
The study findings might shed light on the relatively low effectiveness of H3N2-based vaccines over the past 3 years. Low effectiveness of H3N2-based vaccines is partially due to the inherent difficulties of preparing egg-based H3N2 antigens. H3N2 viruses cannot grow in fertilized chicken eggs without first acquiring an amino acid substitution that abrogates a key glycosylation site in HA antigenic site B, and this egg-adaptation can dramatically alter antigenicity. The study demonstrates that it is difficult to elicit neutralizing antibody responses against H3N2 viruses in some individuals even after natural infection with these viruses. Therefore, irrespective of issues related to H3N2-egg adaptations, it may be inherently difficult to design H3N2 vaccine antigens that are able to elicit neutralizing antibodies in humans that were exposed early in childhood with H3N2 viruses in the 1960s and 1970s.
The study team says that it will be important to continually complete large serological surveys in different aged individuals, including donors from populations with different vaccination rates. A better understanding of immunity within the population and within individuals will likely lead to improved models that are better able to predict the evolutionary trajectories of different influenza virus strains.
Dr Sigrid Gouma, Ph.D., a postdoctoral researcher of Microbiology and first author on the paper said, "Large serological studies can shed light on why the effectiveness of flu vaccines varies in individuals with different immune histories, while also identifying barriers that need to be overcome in order to design better vaccines that are able to elicit protective responses in all age groups."
The study findings also have implications in the coming Influenza 2020/2021 season amidst the COVID-19 pandemic. It should be noted that most of these susceptible individuals would be in their 50s and 40s and most likely to have early chronic diseases like hypertension, diabetes, cardiovascular problems etc. It is also important for these groups not just those in high risk groups like above 60s, being obese and having other comorbidities to also take extra precautions and measures in the coming cooler seasons which also coincide with the flu season.
For more articles and preparations for the coming Influenza 2020/2021
season, keep on logging to Thailand Medical News.