maternal antibodies were no longer
sufficient (4). Similarly, long ago, yellow
fever virus infected native inhabitants in
tropical countries of Africa and America
shortly after birth in the presence of
maternal antibodies. The infection gener-
ally developed without symptoms, but
induced lifelong immunity so that the
disease was mostly observed among newly
arriving foreigners, such as workers build-
ing the Panama Canal and British, French,
Spanish, and American soldiers involved
in wars in the Caribbean (5, 6). Thus, tak-
ing maternal antibodies into account will
probably also be critical to a rational epi-
demic risk assessment in human influenza.
Biochemical Institute of the Christian
Albrechts-University at Kiel, Kiel, 24098, Germany.
1. H. Lemke, Crit. Rev. Immunol .36, 13 (2016).
2. H. Lemke et al., Autoimmun. Rev. 8, 394 (2009).
3. S. Modrow, D. Falke, U. Truyen, Molecular Virology German
(Spektrum Akad. Verlag, Heidelberg, 2003).
4. N. Nathanson, J. R. Martin, Am. J. Epidemiol.110, 672
5. G.C.Kohn, Encyclopedia of Plague and Pestilence: From
Ancient Times to the Present (Facts on File, New York,
ed. 3, 2008).
6. J.S.Marr,J. T.Cathey, J. Public Health Manag. Pract. 19,77
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 (5–7), 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.
Katelyn M. Gostic,1 Monique Ambrose,1
James O. Lloyd-Smith1,3*
1Department of Ecology and Evolutionary Biology,
University of California, Los Angeles, Los Angeles,
CA 90095, USA. 2Department of Ecology and
Evolutionary Biology, University of Arizona, Tucson,
AZ 85721, USA. 3Fogarty International Center,
National Institutes of Health, Bethesda,
MD 20892, USA.
*Corresponding authors. Email: worobey@email.
arizona.edu (M. W.); firstname.lastname@example.org (J.O. L.-S.)
1. J. Lessler et al ., PLOS Pathog .8, e1002802 (2012).
2. T.Francis, Proc. Am. Philos. Soc.104,572(1960).
3. H.Lemke,R.I. Tanasa,A. Trad, H.Lange, Autoimmun. Rev.
8, 394 (2009).
4. R. Bodewes et al ., Clin. Vaccine Immunol .18, 469 (2011).
5. J. H. Kim, I. Skountzou, R. Compans, J. Jacob, J. Immunol.
183, 3294 (2009).
6. R. G. Webster, J. Immunol .97, 177 (1966).
7. Y. Li et al ., J. Exp. Med .210, 1493 (2013).
8. S. Cobey, S. E. Hensley, Curr. Opin. Virol .22, 105 (2017).
A child suffering from polio in Nigeria. If polio
exposure occurs after infancy, maternal antibodies
no longer provide protection from the disease.
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