Maternal antibodies' role in immunity—Response

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Science  17 Feb 2017:
Vol. 355, Issue 6326, pp. 705
DOI: 10.1126/science.aam7389

Our study demonstrated strong statistical support for “childhood hemagglutinin (HA) imprinting,” in which individuals exhibit lifelong immune protection against influenza A viruses genetically similar to the first influenza virus encountered in childhood. Immune imprinting (i.e., preferential recall of adaptive responses primed early in one's immune experience) is also known to influence seasonal influenza epidemiology (1, 2), but the immunological processes underpinning observed imprinting patterns are not well understood. Thus, we welcome Lemke's proposal that maternal antibodies may play a role.

Maternal antibodies can influence the development of a child's immune repertoire in many ways (3), but Lemke's hypothesis that imprinting results from primary influenza exposure shortly after birth, while maternal antibodies are still present, seems inconsistent with data on influenza virology and epidemiology. Unlike the historic examples of endemic yellow fever and poliovirus that Lemke cites, primary influenza A exposure often occurs well after infancy. On average, humans preferentially recall influenza immune responses primed around age 7 (1). Except in years of unusually intense influenza circulation, only 20 to 35% of children encounter an influenza virus in the first year of life (4), but the strong effects detected in our study imply that HA imprinting is much more ubiquitous.

Lab evidence also suggests imprinting can occur in the absence of maternal effects. For example, several studies have induced imprinting in weaned lab mice and ferrets (57), and the phenomenon may arise simply from competition between memory and naïve B cells [reviewed in (8)]. We encourage continued interdisciplinary discussion on the mechanisms underlying immune imprinting phenomena. As Lemke suggests, insights into these mechanisms are needed, and have great potential to inform epidemic and pandemic risk assessment.


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