Researchers have generated a new anti-flu antibody that demonstrates long-lasting and universal protection from a wide variety of influenza A and B viruses, including avian-borne strains like H1N1. According to the results, the rapid onset of comprehensive flu protection it achieves may be able to provide flu protection for an entire flu season, particularly in the elderly or immunocompromised. What's more, their approach shows promise as a preventative measure that could be immediately effective at the onset of an influenza pandemic. Seasonal flu epidemics and the threat of avian-borne influenza pandemics has created a need for comprehensive flu prevention strategies. Although influenza vaccines are currently the most widely used tool in the management and prevention of epidemics worldwide, their effectiveness between seasons and populations remains limited. Certain populations, like the elderly or those with weakened immunity, are a greater risk for infection and often respond poorly to vaccination. Furthermore, the illness itself is highly variable and as a result, vaccines must be matched to specific virus strains circulating each flu season. Widespread success of new alternative therapies based on broadly neutralizing antibodies (bnAbs) has remained elusive, largely due to a similar lack of coverage between influenza A and B viral strains and to the need for multiple high-dose injections to maintain protection. Here, Nick Laursen and colleagues present a new strategy for achieving long-lasting flu virus protection based on broadly neutralizing single-domain antibodies (sdAbs) isolated from llamas immunized with flu vaccines. From these sdAbs, Laursen et al. generated a highly potent multi-domain antibody (MDAb), antibodies that can target multiple antigen epitopes, called MD3606. In mice treated intranasally using an adenovirus vector, the antibodies provided near-universal protection against both influenza A and B viruses. What's more, old and immunodeficient animals were shown to be protected from lethal doses of avian influenza H1N1. If these preclinical findings translate into humans, the approach may be a powerful tool to fight flu in vulnerable populations currently not covered by traditional vaccination.