According to researchers an experimental vaccine produced to offer protection against the H5N1 strain of bird flu presently causing havoc across the world, only appears to work at the very highest doses.
The researchers say this means it will be much harder than first thought to protect the population against a pandemic.
The vaccine which was produced by Sanofi-Aventis is based on an H5N1 virus that killed a Vietnamese man in 2004 and it appears only a satisfactory immune response was seen in volunteers at two doses of 90 micrograms each, 12 times more than is needed for the annual seasonal flu shot.
The H5N1 flu virus has the capacity to cause a severe worldwide epidemic, with high attack rates, large numbers of deaths and hospitalizations, and wide disruption; effective vaccines against such viruses in humans are in urgent need.
Dr. John Treanor of the University of Rochester in New York and his team of colleagues, tested Sanofi-Pasteur's experimental H5N1 vaccine and found that the 90-microgram dose was the only one which produced antibody responses.
The study involved 451 healthy adults 18 to 64 years of age who were randomly assigned to receive two intramuscular doses of an influenza A (H5N1) vaccine of 90, 45, 15, or 7.5 µg of hemagglutinin antigen or placebo.
The subjects groups were then monitored for 56 days; serum samples taken before each vaccination and again 28 days after the second vaccination and were tested for H5 antibody.
The most common side-effect for all doses of vaccine was some slight pain at the injection site.
These results however indicate that there is in fact only enough H5N1 vaccine available in the U.S. to protect about 4 million Americans in a pandemic.
This would probably be used for key health-care workers and people working to make the vaccine.
The rest of the population would be relying on public-health measures such as closing businesses, schools and using protective equipment such as masks and gloves until an effective and sufficient amount of vaccine was produced.
The researchers say trials are now underway in elderly persons, persons with impaired immunity, or children, who may have a different response.
The H5N1 avian influenza virus has swept out of east Asia across to Europe and down into Africa, with frightening speed in recent months, spread in the main by wild birds.
Experts believe within a year or two it will become entrenched in wild birds across the globe.
It remains a predominantly bird disease and is difficult for humans to catch, but has nonetheless infected 186 people in eight countries and killed 105, according to the World Health Organisation.
Experts fear the virus could evolve into a form passed easily from human to human, causing a pandemic that could kill tens of millions.
Influenza viruses mutate quickly and it is nigh impossible to prepare a vaccine in advance that would precisely match a pandemic strain.
Supplies of flu vaccines are limited because of low demand, despite the fact that seasonal influenza kills more than 250,000 people every year globally.
Various organisations and drug companies are currently working on developing H5N1 vaccines, and across the globe 900 million doses could be produced at a push.
The United States alone would need vaccine to protect 300 million people, and to date 83 million doses is the most companies have ever made for the U.S. market.
More than 30 trials are underway, many of which look at ways to extend the vaccine by lowering the dose and adding other drugs to boost the immune response and lower the actual vaccine dose needed.
Some are also looking at faster and more modern production methods.
Treanor believes with two 90-microgram doses needed to produce a satisfying immune response, current manufacturing capacity falls far short.
The common annual flu vaccine mixes the three most common circulating strains of flu at 15 micrograms each while a pandemic vaccine would probably only use one strain. As a rule people only need a single dose of seasonal flu vaccine.
The report is published in the New England journal of Medicine.