Research ArticleInfluenza

Vaccine-Induced Anti-HA2 Antibodies Promote Virus Fusion and Enhance Influenza Virus Respiratory Disease

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Science Translational Medicine  28 Aug 2013:
Vol. 5, Issue 200, pp. 200ra114
DOI: 10.1126/scitranslmed.3006366

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The (Mis)match Game

Even the most beneficial things—like vaccines—sometimes have a downside. Learning what causes the downside is critical for avoiding it. In the case of viral vaccines, there have been some reports of rare vaccine-induced disease enhancement—for example, vaccine-associated enhanced respiratory disease (VAERD) for influenza. Khurana et al. now report that mismatched strains of the same subtype of influenza may lead to VAERD in pigs.

The authors vaccinated pigs with whole inactivated H1N2 influenza virus. These pigs had enhanced pneumonia and disease after infection with another strain—pH1N1. Looking more closely, the authors found that the immune sera from the H1N2-vaccinated pigs contained high titers of cross-reactive hemagglutinin antibodies. These antibodies actually enhanced pH1N1 infection in cell culture by promoting virus membrane fusion activity, and this enhanced fusion correlated with lung pathology. This mechanism of VAERD should be considered when devising strategies to devise a universal flu vaccine.

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