The high mutation frequency of genes encoding influenza virus HA and neuraminidase prompts the need for yearly vaccination against circulating seasonal influenza virus strains. In Science, Impagliazzo et al. demonstrate the feasibility of eliciting protective broadly neutralizing antibodies to multiple heterologous strains of influenza virus. The design involves the rational introduction of specific mutations in sequence encoding the HA stem region that stabilize its trimeric conformation upon removal of the HA head region, which often masks the protective stem epitopes. The resulting 'mini-HA' has structure and glycosylation similar to that of full-length HA. These mini-HA constructs are very immunogenic in mice and monkeys and elicit broadly neutralizing antibodies that prove to be protective against heterotypic influenza virus variants. These findings offer proof of principle that an universal vaccine against influenza virus is achievable.

Science (24 August 2015) doi:10.1126/science.aac7263