Low-dose bird flu vaccine tested on humans

The first clinical trials of a low-dose H5N1 bird flu vaccine are already under way, New Scientist can reveal.

Agnes Hoffenbach, head of pandemic research at manufacturer Sanofi Pasteur, says the results will be ready by December 2005. The news came as the US awarded a $100-million contract to the French-owned vaccine maker to produce a vaccine against H5N1 bird flu on Thursday. The deal is the first major cash order for the vaccine, which drug company officials at an international meeting in Malta this week said will greatly accelerate the development of bird flu vaccines elsewhere in the world.Crucially, Sanofi Pasteur’s trial is testing low doses of killed vaccine virus combined with adjuvant – a chemical that stimulates the immune system.Earlier in 2005, the US conducted the first clinical trials of another H5N1 vaccine made by Sanofi Pasteur (which is also the only firm which makes standard flu vaccine in the US). But those trials were on virus formulated without an adjuvant, in the 15 and 45-microgram doses now used in vaccines for ordinary flu.As New Scientist reported at the time, previous experimental work on bird flu suggested that without adjuvant these doses of the virus would be unlikely to elicit much of an immune response. Barrier to developmentIn August, Anthony Fauci, head of the US National Institute of Allergy and Infectious Diseases, revealed that this was exactly what happened: to get a significant immune response people needed to be given 90 micrograms of killed vaccine virus, in two doses four weeks apart.That is 12 times as much virus as is needed to make an effective vaccine out of an ordinary influenza virus. That in turn means that the world’s vaccine-making capacity would be able to make a mere 25 million doses a year.The Sanofi Pasteur trials currently under way are believed to involve doses as low as 3.5 micrograms, which if effective would quadruple the number of vaccine doses the world could produce per month.The barrier to development has been the availability of public money, or at least promises to purchase the vaccine, without which commercial companies cannot fund large-scale clinical trials. So far, Canada, Australia and Japan have pledged public money for vaccine trials, but none has started yet. France has pledged to buy enough vaccine for its population, and in August the UK asked companies to tender bids, but no firm figures have emerged. In Malta this week, Germany pledged E20 million to fund vaccine trials. On Friday, Italy announced it would spend E50 million on vaccines, after announcing purchasing contracts with three unspecified companies.Drug company officials in Malta pointed out that Europe produces 70% of the world’s flu vaccine. Considering that, and compared with the $350 million the US has so far invested in testing and producing pandemic vaccine, they said Europe’s involvement had so far been puny.But the US order “will drive investment in R&D”, says Bram Palache, global medical affairs director of the Belgian-owned vaccine firm Solvay. “More countries will decide they need this kind of contract. The snowball is starting to roll.”(Source: New Scientist: Debora MacKenzie: September 2005.)