— As vaccine manufacturers struggle to make a standard flu vaccine for the deadly H5N1 bird flu, US scientists have found that a totally different approach might work better.
A live synthetic virus carrying the surface proteins of H5N1, and simply squirted up the noses of test animals, has induced the kind of wide-ranging immunity necessary to make it worthwhile stockpiling vaccine before a pandemic. Tests are already underway in humans.
Most flu vaccines are injected, and contain killed virus. But H5N1 vaccine has been stubbornly ineffective prepared this way two shots containing large amounts of virus or novel, still-unlicensed additives have been needed for recipients to develop immunity, and even then not in all people tested. H5N1 vaccine virus also grows very slowly in production plants, for reasons as yet unknown.
Worse still, what little information is available suggests that these killed vaccines do not induce immunity that cross-reacts with other strains of H5N1. This is crucial if we are to stockpile vaccine ahead of any H5N1 pandemic, as it is impossible to predict the precise strain (see Today's bird flu vaccines will have to do here).
So the new trials, led by Kanta Subbarao at the National Institutes of Allergy and Infectious Diseases in Bethesda, US, represent good news. The researchers used a live, weakened flu virus carrying surface proteins from H5N1. Squirted up the noses of test animals, the spray protected mice and ferrets completely after just two doses, and kept mice from dying from later H5N1 infection after only one dose.
Most importantly, vaccines made from H5N1 strains isolated in either 1997, 2003 or 2004 protected against the other viruses, and against H5N1 taken from Indonesia in 2005. These viruses have the kinds of small differences that might emerge between the H5N1 circulating now and a pandemic strain.
We need a vaccine capable of inducing an effective human immune response against a range of H5N1 viruses that may emerge in future, says Subbarao. While killed virus vaccines induce mainly antibodies, the live synthetic virus induces more cell-mediated immunity, based on blood cells called lymphocytes. That tends to be more broadly reactive with different strains, say vaccine experts.
The live vaccine was based on a weakened flu virus developed by Medimmune of Gaithersburg, Maryland, US, which already markets it as a nose-spray vaccine for ordinary flu. When fitted with surface proteins from H5N1 the live vaccine virus remained harmless, even to chickens, which are extremely sensitive to H5N1. Nonetheless, the 20 people who received the live vaccine in June are in isolation to prevent any virus escaping.
Journal reference: PLoS Medicine (vol 3, e360)