Research ArticleInfluenza

Neutralizing Antibodies Against Previously Encountered Influenza Virus Strains Increase over Time: A Longitudinal Analysis

Science Translational Medicine  14 Aug 2013:
Vol. 5, Issue 198, pp. 198ra107
DOI: 10.1126/scitranslmed.3006637

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Only a Matter of Time

In the fast-paced world of scientific research, most conclusions are drawn on few—or single—time points or with animal models that may accelerate—but not always accurately reproduce—disease progression. Longitudinal analyses are rare. Indeed, this is the case in influenza virus research, where it is thought that previous infections influence the outcome of subsequent infections, but little is actually known about how sequential exposures to antigenically diverse viruses affect the antibody response to influenza A viruses. Now, Miller et al. use samples obtained over a 20-year period from 40 individuals involved in the Framingham Heart Study to look at antibody titers to seasonal and pandemic influenza strains over time.

The authors find longitudinal increases in neutralizing antibodies to previously encountered seasonal and pandemic flu strains. This increase was not age-dependent because it was observed against strains encountered later in life as well as in earlier exposures. Titers to the more conserved hemagglutinin stalk domain increased modestly as well, but no neutralizing antibody titer increase was observed against a more antigenically stable virus (human cytomegalovirus). These results suggest that antigenic variation may drive the hierarchical humoral immune response to influenza strains. The contribution of antigenic variation to antibody titers to the conserved stalk region supports the pursuit of vaccine strategies that increase exposure to antigenically diverse strains of influenza.