To the editor:

Cormac Sheridan's account of efforts to produce improved influenza vaccines (Nat. Biotechnol. 22, 1487–1488, 2004) has important implications for future pandemics. These widespread and deadly outbreaks occur in humans when, perhaps as the result of recombination between human and animal flu viruses, a 'genetic shift' gives rise to significant changes in the major antigen, hemagglutinin, and a virus emerges which contains a hemagglutinin different from those of previously circulating viruses. The result may be major epidemics or pandemics in populations that have no immunity to the new strains; examples include Spanish flu (1918–1919), Asian flu (1957) and Hong Kong flu (1968–1969).

The limitations of current methodology slow our response to the constantly appearing new variants of flu virus, whether pandemic strains or those that result from far more common 'genetic drift'—less consequential mutations—which require the development of a new vaccine every year. Decisions about the viral strains to be included in every flu season's vaccine must be made during the previous winter, and the viruses are then grown in millions of chicken eggs. In the face of a pandemic, this lag could be catastrophic.

Sheridan described various innovative approaches to vaccine development, potentially the most important of which is the use of recombinant DNA techniques to make so-called 'subunit' flu vaccines. Used for two decades to produce hepatitis B vaccine (specifically, the hepatitis B surface antigen), this approach involves cloning a single gene (or a small number of genes) from the virus into bacteria or yeast; grown at large scale, these organisms are the source of the viral gene product(s), which, after being isolated and purified, is used as the vaccine. As Sheridan points out, the culmination of this approach would be a vaccine that elicits an immune response to flu's matrix proteins, which are highly conserved from strain to strain.

Sheridan refers in passing to “unfavorable market conditions”—read: flawed public policy in the United States—that have inhibited innovation and R&D of vaccines. The major purchaser of most vaccines in the United States, the Centers for Disease Control and Prevention (CDC, Atlanta), extracts huge discounts from manufacturers, and arbitrary and excessive regulation by the US Food and Drug Administration (FDA, Rockville, MD, USA) also blocks progress. As a result, innovation has suffered and vaccine producers have abandoned the field in droves, leaving only four major US manufacturers and a few dozen products. There are only two producers of injectable flu vaccine for the US market, for example.

To correct these broad deficiencies, and to stop a potential flu pandemic in its tracks, the US government must take a number of actions. Grant-giving agencies should increase funding for basic research on subunit vaccines, especially those that are cross-subtype-specific; the CDC must stop demanding discounts that discourage manufacturers; and regulators should pursue agreements on 'reciprocity' of approvals so that vaccines and antiviral drugs licensed in certain foreign countries can be marketed in the United States.

In the longer term, Congress could take other steps to improve the climate for vaccine makers, such as offering tax breaks to offset R&D costs; requiring health insurance providers to cover immunizations without the usual deductibles; and stipulating that once the FDA has approved a vaccine, the government would compensate victims of side effects.