Editors' ChoiceInfluenza

Steps Toward a Universal Flu Vaccine

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Science Translational Medicine  20 Jun 2012:
Vol. 4, Issue 139, pp. 139ec107
DOI: 10.1126/scitranslmed.3004464

Each fall, many individuals participate in—and dread—the annual ritual of getting their seasonal flu shot. For continuing protection against influenza, an updated shot must be given each year because the main protective antibodies raised are reactive to portions of the virus that change as strains evolve year to year. Indeed, every year scientists must predict which strains are going to be the most prevalent, and sometimes an unpredictable pandemic strain, such as the 2009 H1N1 virus, gets through. A universal flu vaccine would eliminate the need for this yearly shot as well as protect against pandemic strains. A vaccine that is highly cross-reactive between strains and that raises antibodies against conserved regions of the virus has long been sought, but it has not yet become a reality.

To overcome this bottleneck, Li and colleagues observed antibody responses raised by individuals who had been immunized with the subunit H1N1 vaccine against the 2009 pandemic strain (also known as the “swine flu”). They found that this vaccine, in contrast to the normal seasonal vaccines, induced a rapid expansion of plasmablasts (antibody-producing precursors of plasma cells) that produced antibodies highly cross-reactive with other influenza strains. Several monoclonal antibodies derived from these plasmablasts were reactive to conserved regions of influenza proteins and were able to neutralize strains as divergent as H3N2 and H1N1. Such broadly cross-reactive antibodies have been widely sought after but rarely found. Interestingly, the antibodies found by Li et al. arose from a recall response—that is, preexisting memory B cells capable of responding to the vaccine existed in these patients from previous encounters of influenza.

Why are these antibodies more predominant as a result of pandemic rather than seasonal flu vaccines? It is possible that the relative similarity of the seasonal flu strains is the culprit—new seasonal vaccines that only slightly vary from previous years could amplify the immune response to variable immunodominant epitopes. With a different flu strain such as the pandemic strain, the preexisting immunity might not recognize the variable sites, and the rarer immune response to conserved sites may become amplified. Collectively, these results provide an important proof of concept that a universal vaccine is possible and that a productive infection by influenza may not be necessary to generate these broadly cross-reactive antibodies. Now, the challenge remains to develop a vaccine that can preferentially stimulate these antibodies.

G.-M. Li et al., Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells. Proc. Natl. Acad. Sci. U.S.A. 109, 9047–9052 (2012). [Abstract]

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