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Diluted flu vaccine works well

November 4, 2004 By Helen Pearson This article courtesy of Nature News.

Splitting dose might help to stretch scarce stocks.

In the midst of the United States' flu vaccine shortage, two studies have shown that the jab could still work at a fraction of its normal strength. But doctors say that it may be premature to water down existing supplies.

Fresh supplies of flu vaccine, or ways to eke out the current stocks, have been desperately sought in the United States since early last month, when fears about bacterial contamination forced manufacturers to ditch half the country's supply.

One of the studies, published in the New England Journal of Medicine, shows that the vaccine may offer good protection at just one-fifth of the normal dose. The team, led by Gregory Glenn of the vaccine company Iomai, compared 50 adults who were injected under the skin with the low dose with 50 adults who received the full, standard dose into their muscle1.

In the second study, published in the same journal, a team led by Robert Belshe of St Louis University, Missouri, gave nearly 120 adults an experimental vaccine equivalent to 40% of the full dose, also under the skin. Like the first group, the team found that the reduced dose triggered just as vigorous an immune response as the standard one, although adults over 60 showed a weaker response2.

Going off-label

Despite the results, regulatory authorities are unlikely to recommend the use of diluted flu vaccine this winter. The studies do not prove decisively that the weaker dose staves off disease during the flu season as effectively as a normal dose, or show what is the best dose for high-risk groups such as young children, the elderly and those suffering chronic diseases.

But doctors facing a shortage of vaccine might now choose to administer a smaller dose off-label, Belshe says: "Doctors and their patients could try this."

Earlier research had shown that halving the dose of vaccine injected into muscle triggers immune responses equal to a full dose. The new studies reveal that the dose can be slashed even further if it is injected shallowly, in between layers of the skin. This is done with a very tiny needle, forming a temporary bubble of liquid.

The skin is thought to be better at triggering an immune response than muscle, because it is constantly exposed to microbes and is policed by white blood cells, which ward off the invaders. These cells eat up the viral proteins in the vaccine and travel to the lymph nodes where they fire up the body's immune system to produce flu-fighting antibodies.

Vaccines delivered to the skin are already being investigated for rabies and hepatitis B vaccines, and some companies are working on alternative ways to deliver the flu vaccine to the skin or other sites. Maryland-based Iomai, for example, is developing a skin patch that is placed over the stab site of the injection to boost the normal response. "It's a hot field," Glenn says.


  1. Kenney R. T., et al. NEJM, 351. (2004).
  2. Belshe R. B., et al. NEJM, 351. (2004).


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