An intradermal vaccine equipped with an immune response-boosting adjuvant protected ferrets and humans against one of the more lethal strains of pandemic flu, researchers report. Their approach represents the first adjuvanted vaccine designed for intradermal delivery, which, because it does not require immunization expertise (the microneedle involved is unable to penetrate deep tissue or blood vessels) could one day be sent through the mail for self-administration. This could greatly alleviate crowds in health care centers in the event of a pandemic outbreak. Rapid production and distribution of vaccines during a pandemic flu outbreak represents a critical global health challenge. Exacerbating matters, vaccines against flu strains with pandemic potential generally yield poor antibody responses compared to vaccines against seasonal flu strains. In recent years, as parts of efforts to make vaccines more effective, researchers have explored adjuvants, agents that enhance the body's immune response to an antigen. Also, they have studied alternative delivery routes, such as intradermal (ID) vaccines, which are injected into the skin. To date, no adjuvant suitable for human use has been developed for intradermal vaccines, however. Here, seeking to create such an adjuvanted vaccine for use in pandemics, Darrick Carter et al. combined three technologies: a hollow microneedle requiring little expertise to use, noninfectious recombinant influenza virus-like particles (VLPs) that produce a stronger immune response than standard inactivated pathogens, and a glucopyranosyl lipid-based adjuvant (GLA) previously shown to boost vaccine effectiveness. In ferrets, just a single administration of the vaccine formulated in an aqueous form of the adjuvant fully protected the animals, the authors say. In a first-in-human trial with 100 participants, the adjuvanted vaccine created no significant adverse effects, and, compared to controls who did not receive the adjuvanted version, those who did showed a stronger immune response. The work provides a future path for developing a vaccine-device combination for distribution by mail and self-administration in case of a pandemic, the authors say.