Ability to Produce Immunity to Influenza A (H3N2) Called Into Question

The results of a recent study published in Nature Communications shows that adults born in the 1960s and 1970s may be less able to produce neutralizing antibodies to modern influenza A (H3N2) virus strains, and thus middle-aged patients may be continuously susceptible to H3N2 viruses.

The study results show that children aged 3 to 10 years had the highest levels of neutralizing antibodies for the viruses. It also showed that most middle-aged adults did not have detectable neutralizing antibody titers against 3c2.A or 3c2.A2 H3N2 viruses. In fact, the lowest titers were measured in patients born in 1967, a year before H3N2’s introduction into human circulation. It should also be noted that there did not seem to be any significant hemagglutinin (HA) antigenic changes between the 2014-2015 3c2.A and 2017-2018 3c2.A2 strains, which usually results in at least some immunity after exposure.

The authors contend that childhood infections that current middle-aged adults experienced in the 1960s and 1970s primed antibody responses that are reactive but not neutralizing against modern 3c2.A H3N2 viruses. In short, individuals could produce nonneutralizing antibodies that could bind to the viruses’ HA but not prevent infection.

Although the exact reason for the decreased immune response in middle-aged adults remains unclear, these findings suggest that this patient population may be continuously susceptible to the 3c2A H3N2 infection, even with immunization. It also provides some insight into the high infection rates of adults during seasons when H3N2 is the dominant circulating strain and why 3c2A viruses continue to circulate despite minimal to no antigenic drift. The study results also raise questions about the existence of other age-related immune responses.

Further and larger studies are needed to fully evaluate immunity among different aged groups and birth years, investigators said.

Data from such studies could lead to a significant breakthrough in the understanding of immunity and subsequently change influenza prevention approach.

REFERENCE

Gouma S, Kim K, Weirick ME, et al. Middle-aged individuals may be in a perpetual state of H3N2 influenza virus susceptibility. Nat Commun. 2020;11(1):4566. doi:10.1038/s41467-020-18465-x