Preferential induction of cross-group influenza A hemagglutinin stem–specific memory B cells after H7N9 immunization in humans

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Science Immunology  14 Jul 2017:
Vol. 2, Issue 13, eaan2676
DOI: 10.1126/sciimmunol.aan2676

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Stemming the tide of influenza

A universal flu vaccine would prevent the need for yearly flu shots, but successful development has been hampered by the diversity and adaptability of the influenza virus. Andrews et al. compared B cell responses to the relatively conserved stem region of the influenza cell surface molecule hemagglutinin (HA) in humans vaccinated with either group 2 H7N9 or group 1 H5N1. They found that the stem-targeted memory B cells after H7N9 vaccination recognized both group 1 and group 2 influenza subtypes, whereas H5N1 vaccination induced responses primarily to group 1 subtypes. These data suggest that a group 2 stem immunogen, administered in the proper conditions, would have a higher likelihood of eliciting cross-group protection.


Antigenic drift and shift of influenza strains underscore the need for broadly protective influenza vaccines. One strategy is to design immunogens that elicit B cell responses against conserved epitopes on the hemagglutinin (HA) stem. To better understand the elicitation of HA stem–targeted B cells to group 1 and group 2 influenza subtypes, we compared the memory B cell response to group 2 H7N9 and group 1 H5N1 vaccines in humans. Upon H7N9 vaccination, almost half of the HA stem–specific response recognized the group 1 and group 2 subtypes, whereas the response to H5N1 was largely group 1–specific. Immunoglobulin repertoire analysis of HA-specific B cells indicated that the H7N9 and H5N1 vaccines induced genetically similar cross-group HA stem–binding B cells, albeit at a much higher frequency upon H7N9 vaccination. These data suggest that a group 2–based stem immunogen could prove more effective than a group 1 immunogen at eliciting broad cross-group protection in humans.

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