To meet this threat, pandemic preparedness goals in the US include improving manufacturing capability to supply the necessary quantities of vaccine within six months of the declaration of a pandemic, and stockpiling pre-pandemic vaccines that might provide complete or partial coverage against a new virus. To achieve these goals, new recombinant technologies and adjuvants are needed that will shorten production cycles, maximize vaccine immunogenicity, and increase global vaccine supply. Effective adjuvants can augment protective immune responses using minimal antigen, thus providing a dose-sparing benefit that increases vaccine coverage. The most widely used class of adjuvants for Influenza vaccines are oil-in-water emulsions including MF59, ASO3, and AF03. These adjuvants contain shark-derived squalene that is microfluidized in buffer and surfactants to generate oil particles, averaging 100�C160 nm in diameter, suspended in water. Collectively, these emulsions induce seroprotective antibody responses to inactivated H5N1 vaccines that exceed approvable endpoint criteria in humans and provide a significant dose sparing effect. In addition, they mediate the priming and production of cross-reactive H5N1 antibody responses that recognize drifted strains of virus. Despite the fact these emulsions are approved for human use in the European Union, there has not been a product Artemisinic-acid registration that includes emulsion-based adjuvants in the US. Another type of adjuvant targets Toll-like receptors on antigen presenting cells and the induction of Th1-mediated immune responses. TLR4 agonists are highly effective in experimental and clinical settings with the most advanced product being MPL, a component of the human papilloma virus vaccine, CervarixH. Vaccine adjuvants are needed for increasing the breadth of protective immunity against Influenza viruses and for improving vaccine manufacturing capacity. Collectively, adjuvants stimulate innate immune pathways that facilitate dendritic cell activation and antigen presentation. Oil-in-water emulsions are very effective adjuvants for pandemic influenza vaccines and stimulate approvable HI titers in adults, young children and infants at substantially reduced doses of antigen. These adjuvants are prepared by mixing shark-derived squalene and egg phosphatidylcholine oils with an Kaempferide aqueous buffered solution containing glycerol and the surfactant poloxamer 188, followed by high pressure homogenization and filtering. Mechanistically, emulsions induce a chemokine-driven gradient at the site of injection that recruits leukocyte infiltration and antigen transport to local lymph nodes, and their induction of broadly reactive CD4 T cells predict the rise of neutralizing antibody titers after booster immunizations. The humoral responses induced by these adjuvants involve antibody epitope spreading from the HA2 portion of HA to large conformational domains in the globular HA1 region of HA, which correlate with broad cross-clade neutralization. Despite their utility, vaccines containing emulsion-based adjuvants have not been approved in the United States, and ongoing large-scale epidemiological studies are evaluating their safety.