Editors' ChoiceInfluenza

Influenza antibody archaeology

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Science Translational Medicine  06 Jan 2016:
Vol. 8, Issue 320, pp. 320ec4
DOI: 10.1126/scitranslmed.aad9764

An interesting aspect of immunity against influenza viruses lies in the influence that early exposures to different strains of the virus have on the antibodies generated over the course of one’s life. To understand this relationship between early exposures and current influenza antibody repertoire, Schmidt et al. studied the ontogeny of a panel of broadly neutralizing antibodies from a single individual born in 1990. The authors found that the antibodies were derived from germline antibodies that reacted only with virus strains, which circulated in the first years of the subject’s life, from 1990 to 1993. Over time, and presumably in response to sequential exposures to newer virus strains, the germline, unmutated, antibodies acquired changes that increased their affinity and breadth of binding to newer strains. Ultimately, the antibodies could neutralize many H1N1 virus strains that had emerged over a 30-year period from 1977 to 2007.

Early influenza exposures are known to determine, to some degree, the pool of B cells that will respond to viral strains encountered later in life, but it is not yet known how this phenomenon may impact responses to a new generation of vaccines that are designed to provide broad immunity against influenza viruses. The work by Schmidt et al. suggests that a vaccine regimen designed to generate broad influenza immunity should begin with a priming antigen that activates B cells with the greatest potential for broadly neutralizing activity. Although the antibodies elicited by that initial antigen may not demonstrate breadth, this study suggests that subsequent vaccination with a series of slightly different antigens may drive affinity maturation and selection of B cells capable of providing broad protection against influenza viruses.

A. G. Schmidt et al., Immunogenic stimulus for germline precursors of antibodies that engage the influenza hemagglutinin receptor-binding site. Cell Rep. 13, 2842–2850 (2015). [Full Text]

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