Research ArticleInfluenza

Elicitation of Broadly Neutralizing Influenza Antibodies in Animals with Previous Influenza Exposure

Science Translational Medicine  15 Aug 2012:
Vol. 4, Issue 147, pp. 147ra114
DOI: 10.1126/scitranslmed.3004273

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Stemming the Flu Shot

Every year, the influenza virus gets a makeover so remarkable our immune systems barely recognize it. The virus mutates its surface antigens, which make it possible to evade immune attack even in people who have suffered flu in previous years. Yet, some parts of the surface antigen hemagglutinin (HA)—such as the stem region—are critical for infection and thus conserved. Consequently, scientists have targeted this region in strategies to build a universal vaccine. Unfortunately, the lack of widespread natural immunity to the stem region raises red flags about the efficacy of this method: What if previous immunity prevents the induction of broadly protective antibodies? Wei et al. now find that in mice and ferrets, neither previous infection nor previous vaccination prevents the induction of broadly neutralizing antibody responses.

The authors primed mice with a DNA vaccine and then boosted with inactive influenza and found that HA stem–directed antibodies were elicited regardless of preexposure route. In ferrets, prime-boost with adenoviral vectors conferred protection against influenza challenge. Indeed, immunogenicity was actually enhanced in animals previously exposed to a divergent flu strain. Although these studies must be translated to humans, the new data suggest that administration of a successful universal flu vaccine won’t be restricted to people who have never before been exposed to the virus.