Every winter the seasonal flu vaccine gets reformulated. The World Health Organization recommends which viruses to put into the vaccine to impart immunity against the strains that are considered most likely to spread. For example, this year's vaccination cocktail will include the antigens isolated from flu strains first spotted in the Solomon Islands, Wisconsin and Malaysia. This continual updating results from the flu virus's ability to mutate in response to the human body's immune defenses. This ability to mutate and spread quickly also lurks at the core of pandemic fears surrounding bird flu, but a new vaccine formulation tested in ferrets and human blood appears to confer protection against a variety of mutated avian influenzas.

Researchers from GlaxoSmithKline (GSK) at the IX International Symposium on Respiratory Viral Infections in Hong Kong this week revealed that a new vaccine that had previously proved effective in protecting people against a strain of H5N1 bird flu from Vietnam also protected them from another bird flu variant isolated in Indonesia. "These two strains, when evaluated for antigenic relatedness, showed an eight- to 16-fold difference for a reference antiserum," says Bruce Innis, vice president and director of clinical research and development and medical affairs at GSK Biologicals. In other words, the vaccine protected the blood from 400 volunteers from two very different strains of bird flu.

Most vaccines only work against the virus they are specifically designed to fight. "When you get vaccinated with a flu vaccine, your antibody response tends to be narrowly directed at the virus that was targeted by the vaccine," explains John Treanor, an immunologist at the University of Rochester. "When we're vaccinating against pandemic flu, with no prior exposure, you would expect the response to be narrowly focused." Yet, in blood tests, the GSK vaccine effectively neutralized both the Vietnamese and Indonesian strains.

Further tests in ferrets showed that a propriety adjuvant system—extra agents such as aluminum salts in a vaccine that enhance its effectiveness—may be behind the effect. Animals given the Vietnam vaccine without the adjuvants died after being exposed to the Indonesian strain. "All of the control animals died and the great majority [(22 out of 23)] of the vaccinated animals survived," Innis says. "Is it the adjuvant system that is producing the protective effect? In our view, the answer is yes."

Exactly how the adjuvant system works remains a mystery as well—even more so because GSK will not reveal what adjuvant system it used, revealing only that there are 25 new adjuvants being analyzed. "Does it somehow cause a whole new spectrum of shapes on the surface proteins of the flu virus to be recognized? Or does it increase the amplitude of the immune response?" Innis asks. "Those tests haven't been done yet, but effects that are present at very low doses with the adjuvant system are almost completely absent at eight times that dose without the adjuvant system." Its effectiveness is clear: the immune response in human blood was 25 times stronger with the adjuvant present than without it.

This raises the prospect that the new vaccine could cut down on the amount of antigen required to manufacture it as well as confer broader protection—without the need for reformulation. The U.S. Department of Health and Human Services has already contracted with GSK for $40 million worth of antigens to the Indonesian strain with an option to purchase the mysterious adjuvant system, too. This could lead to the ability to stockpile an effective vaccine against the much-feared potential bird flu pandemic. As Treanor says: "Since you don't know which one, if any, of the bird flu strains might emerge as the pandemic strain, there is some advantage in an antibody that might be able to affect members of multiple strains."

Innis adds: "We know that the job of flu vaccine is to protect against not only what you put in the vaccine but also things that might occur in the future because [evolution] is ongoing."