With the use of a technique known as reverse genetics, a prototype of infl uenza virus (H5N1) has been produced for the development of an inactivated subvirion vaccine. The gene segments encoding HA and NA were derived from A/Vietnam/2004, and all other genes were derived from the backbone (A/PR/8/34) virus, commonly used as a platform for infl uenza vaccine production. The HA gene was further modifi ed to replace the stretch of 6 basic amino acids at the cleavage site, and the resulting virus was avirulent in chickens. In a recent trial, healthy adult volunteers were given 2 intramuscular doses of this inactivated infl uenza (H5N1) vaccine. This split vaccine induced an antibody response predictive of protection in 54% of healthy adults tested, but only when given intramuscularly at high doses (two 90-μg shots) (16) . The large amounts needed (2 doses of vaccine, each 6 times the dosage of that used in a standard infl uenza shot) means that hundreds of millions of doses are needed to tackle a pandemic. Dose-sparing approaches, including the use of an effi cient nontoxic adjuvant to boost persons' immune responses, may improve the vaccine. Another trial was performed with 300 healthy participants 18-40 years of age, in which aluminum hydroxide adjuvant was used with similar split-virus vaccine (17) . However, the alumadjuvanted vaccines did not improve the immunogenicity or percentage of seroconversion at lower vaccine doses and only slightly improved immunogenicity at the 30-μg dose. This diffi culty underscores the importance of vigorous fundamental research to address the question of how to increase the immunogenicity of such vaccines, whether by better antigen presentation or by choosing alternative routes of administration, so that lesser amount of antigen could be given to induce protective response. The present annual global production capacity is ≈300 million doses of trivalent vaccine containing 15 μg HA per strain. This is equivalent to 900 million doses of monovalent vaccine, a quantity markedly insuffi cient for the world's 6.5 billion people. Clearly, dose-sparing formulations are urgently needed.