A new approach to improving vaccine supplies in the event of an influenza pandemic is reported online in Mucosal Immunology (http://www.nature.com/mi) this week. The study compares delivery methods of the current vaccine in an animal model and shows that a lower dose delivered to the site of infection, gives better protection against influenza than the normal dose as it is currently delivered. One of the most serious challenges facing human health today is preparing for the next influenza pandemic. Influenza is a major global health issue; in the USA alone influenza infections are associated with an average of 36,000 deaths and 114,000 hospitalisations each year. Mucosal surfaces are linked by an integrated immune system, and protection at mucosal surfaces may be best induced by vaccination at these same sites. Despite this, the vast majorities of approved vaccines are delivered by injection and induce predominantly systemic immunity, even when targeting mucosal pathogens. Australian researchers used a sheep model to test whether immunization at the site of influenza infection, directly in to the lung could improve protection. They found that compared to the currently available vaccine, significantly lower doses of vaccine delivered directly to the lung resulted in better protection against subsequent influenza infection. This finding may have significant implications in the event of a pandemic when vaccine supplies may not meet demand. Abstract: Using a large animal model, we evaluated whether delivery of influenza vaccine via its mucosal site of infection could improve vaccine effectiveness. Unexpectedly, pulmonary immunization with extremely low antigen doses (0.04 ug influenza) induced serum antibody levels equivalent to those resulting from a current human vaccine equivalent (15 ug unadjuvanted influenza, subcutaneously) and vastly superior lung mucosal antibodies. Induction of this potent response following lung vaccination was dependent on addition of ISCOMATRIX adjuvant and deep lung delivery. Functional antibody activity, marked by hemagglutination inhibition, was only present in the lungs of animals that received adjuvanted vaccine via the lungs, suggesting this approach could potentially translate to improved protection. The 375-fold reduction in antigen dose and improved mucosal antibody responses, compared to the current vaccine, suggests that mucosal delivery via the pulmonary route may be particularly relevant in the event of an influenza pandemic, when vaccine supplies are unlikely to meet demand.