Original Antigenic Sin and Pandemic (H1N1) 2009

To the Editor: While pandemic (H1N1) 2009 was in its earliest stages, age distribution data indicated surprisingly few cases among persons >65 years of age. The initial assumption was that few persons >65 years of age had yet to be exposed. However, as more data became available from Mexico, Australia, and the United States, the age distribution pattern persisted (1). This observation raised the question about whether older persons were protected from infection with an infl u-enza virus A (H1N1) strain acquired many years ago. Indeed, data from the Centers for Disease Control and Prevention showed that approximately two thirds of older persons have evidence of immunity to pandemic (H1N1) 2009 virus. In 1960, Thomas Francis proposed the hypothesis of original antigenic sin, a phenomenon whereby a person who as a child was fi rst exposed to a specifi c infl uenza virus A would, throughout life, mount an immune response to the virus of childhood , even when exposed to other antigenically dissimilar infl uenza viruses. In effect, the original antibody response generated by the immune system against a specifi c infl uenza viral strain was hypothesized to have colored all future responses to infl u-enza (2). Serologic responses of humans and other mammals have supported this theory. A new hemagglutinin (HA) subtype emerged in 1918 that was responsible for the pandemic that year. Through 1956, the strain evolved, accumulating mutations. In an era before infl uenza viruses were subtyped was performed, the original 1918 infl uenza virus A (H1N1) was dubbed a swine strain, whereas the virus of the 1930s was known as infl uenza A. However, the amount of drift accrued by 1947 was enough to render the seasonal vaccine of the time ineffective, and the new drifted virus strain was named A′. Throughout the period, the virus continued to be the subtype H1N1, as it is now designated. In 1956, Davenport and Hennessy examined the antibody responses of 3 different age cohorts, each of which received different monovalent infl u-enza vaccines prepared with vaccine strains circulating at different earlier periods (3) (Table). Prevaccination serum samples confi rmed the presence of antibodies specifi c to the infl uenza virus that circulated during each respective cohort's childhood. Each of the 3 monovalent vaccines was administered to a group from each age cohort. Vaccination directed toward infl uenza strains distinct from the virus of childhood not only resulted in …