hat epidemiologist Thomas Francis, Jr. (1900–1969) was thinking when pondering certain inexplicable serologic data from a 1946 in. uenza vaccine trial may nev-er be known. Whether in religious reverence for the beauty of science or impish delight fueled by the martini breaks of which he was so fond, Francis coined the term "original antigenic sin" to describe a curious new immunologic phe-nomenon. Elsewhere in this issue, Adalja and Henderson propose that original antigenic sin has altered the popula-tion age–specifi c incidence of infection and disease caused by in. uenza A pandemic (H1N1) 2009 virus and that public health responses must account for the disruption (1). What is original antigenic sin, what is its immunologic basis, and into what sort of trouble is it getting us
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