Human broadly neutralizing antibodies (bnAbs) — which target the highly conserved haemagglutinin (HA) stem of the influenza virus — have recently been identified, raising hopes that a universally protective influenza vaccine may be feasible. Now, two new papers report novel approaches to targeting the HA stem. Using a combination of rational design and library approaches, Impagliazzo et al. engineered stable HA stem antigens, termed 'mini-HAs', by introducing changes into the HA sequence of an H1N1 influenza virus strain. Mini-HA #4900 — which exhibited structural and bnAb-binding properties comparable to those of full-length HA — was highly immunogenic in vivo, conferring complete protection against lethal heterologous and heterosubtypic group 1 influenza virus challenge in mice and significantly reducing fever following sublethal challenge in cynomolgus monkeys. Meanwhile, Yassine et al. used iterative structure-based design to develop H1 HA stabilized-stem (HA–SS) glycoproteins that lack the immunodominant HA head region but retain immunogen antigenicity. They genetically fused HA–SS to the ferritin subunit from Helicobacter pylori to create self-assembling HA–SS nanoparticles (H1–SS–nps) to use as a vaccine. In mice and ferrets, the H1–SS–np vaccine elicited broadly cross-reactive antibodies that completely protected mice and partially protected ferrets against lethal heterosubtypic H5N1 influenza virus challenge.