Potential antigenic explanation for atypical H1N1 infections among middle-aged adults during the 2013-2014 influenza season

NIAID CEIRS | Research Publication Commentary

Linderman SL et al. Potential antigenic explanation for atypical H1N1 infections among middle-aged adults during the 2013-2014 influenza season. Proc Natl Acad Sci USA. 2014 Nov 4.

Influenza viruses have been known to most seriously affect children and the elderly due to their weaker immune systems. During the 2013-2014 influenza season, however, there was a disproportionately high number of middle-aged adults affected by the 2009 H1N1 pandemic influenza virus (pH1N1). It was hypothesized that the unusually high number of influenza infections among this population could have been due to insufficient rates of vaccination in middle-aged adults. In this paper, Linderman et al. suggest an alternate explanation that points to decreased efficacy of the immune response mounted by the middle-aged population.

An individual’s immune response to new strains of influenza is affected by the first strain they encounter because of what is known as “original antigenic sin.” This refers to the propensity of the immune system to mount a response that is governed by immunological memory. When an individual first encounters an influenza infection they develop antibodies to the virus. When that same individual encounters a new strain of the virus (in this case the 2013-2014 strain of pH1N1), the antibody response is dominated by antibodies developed from the individual’s first encounter with H1N1 influenza. This immunological memory may prevent the immune system from developing antibodies that would be more effective against the variant strain.

The strains of seasonal influenza H1N1 that circulated between 1965 and 1979 (the years many middle-aged individuals first encountered H1N1) share a specific region of the hemagglutinin (HA) glycoprotein with the pandemic strain of H1N1 that emerged in 2009. Many middle-aged individuals have antibodies that target this similar region of the virus (the K166 region of the HA glycoprotein). During the 2013-2014 influenza season however, the pH1N1 strain developed a mutation in this area (the K166Q mutation). Linderman et al. performed a hemagglutination-inhibition (HAI) assay to determine whether human antibodies that had been raised against K166 HA could recognize a site-directed K166Q mutation incorporated into the pH1N1 virus using reverse genetics technology. They found that, in vitro, the K166 HA-specific serum was less effective at neutralizing viruses with the K166Q HA mutation. This finding suggests that the antibodies found in a large number of middle-aged adults from their first exposure to H1N1 influenza are ineffective against the pH1N1 that was circulating in 2013-2014.

The 2014-2015 strains of pH1N1 currently circulating in the community also contain the K166Q HA mutation. Given that this region of the virus appears to be immunologically important, Linderman et al. propose updating the influenza vaccines to include a viral strain with the K166Q mutation. While the authors feel updating the vaccine is important to offer the best possible protection, they admit it is unclear if this update would be able to break the original antigenic sin in the middle-aged population.

Emory-UGA CEIRS researchers Dr. Ali Ellebedy and Dr. Rafi Ahmed contributed to the research highlighted in this commentary. The Ahmed lab focuses on studying human B cell responses to influenza virus infection and vaccination. Specifically, they investigate the longevity and specificity of the B cell response to different regions of the HA glycoprotein, as well as how to modify vaccines to induce a better response. Their lab also provides pre- and post-vaccination human sera to the CEIRS community.