TORONTO, April 27 — Vaccinating people against a related influenza strain ahead of time might help overcome delays in getting an avian flu pandemic vaccine into the clinic, according to an international team of researchers.

• Explain to interested patients that while a vaccine against H5N1 avian influenza exists, it takes a substantial dose to induce an immune response.
• Note that this study suggests that prevaccinating people with a related — and possibly mismatched — strain primes the immune system so that a later vaccination with a pandemic strain would boost the antibody response with less vaccine.

Because of the difficulty in making a new flu vaccine, there is likely to be a significant delay — perhaps as long as six months — in producing a medication against an emerging pandemic strain, according to Iain Stephenson, F.R.C.P., of the University of Leicester and colleagues.

But priming people beforehand with a related strain generates a pool of immune cells that can react quickly and provide at least some immunity, Dr. Stephenson and colleagues said online in the Proceedings of the National Academy of Sciences.

The study — released as the world watches a swine flu outbreak — concentrates on the H5N1 avian flu threat, long seen as having the potential to cause a pandemic if it develops the ability to jump directly between humans.

The swine flu outbreak, on the other hand, involves an H1N1 strain of influenza A. The strains of flu are characterized by variations in their hemagglutinin and neuraminidase proteins — the ‘H’ and ‘N’ in the name.

A central issue in preparing a vaccine against the H5N1 avian flu is that several studies have shown it takes two doses — a total of nearly 200 micrograms — to induce an immune response.

Given that manufacturing capacity is likely to be a bottleneck, researchers have been seeking ways to improve the efficacy of the vaccine.

In this study, the researchers found that a previous vaccination against a strain related to the H5N1 flu — an H5N3 strain — increased the response to an H5N1 vaccine, compared with volunteers who had not been primed.

Dr. Stephenson and colleagues are not the first to explore such a ‘prime-boost’ strategy. Last year, American researchers reported a similar study. (See ‘Prime-Boost’ Strategy Might Overcome Avian Flu Vaccine Shortage)

But the earlier study used a pool of people who had been previously vaccinated against another H5N1 strain. When they got a vaccine against the current research strain, they had robust immune responses.

In the current study, the researchers were testing a vaccine against the H5N1 influenza strain known as A/Vietnam/1194/2004 clade 1. All told, 54 adults were given two 7.5-microgram doses, along with an adjuvant called MF59.

Of the 54 volunteers, 24 had been previously vaccinated — with or without the MF59 adjuvant — against a clade 0-like A/duck/Singapore/1997 H5N3 strain during 1999 through 2001.

Another 30 volunteers were not primed. The researchers measured B-cell memory to the H5N1 vaccine, as well as antibody responses to diverse clade 0, 1, and 2 reassortant and wild-type H5N1 viruses.

B cells that reacted to the test vaccine were low in both primed and unprimed volunteers before the vaccination. But by day 21, the frequency of such cells had increased in all groups, with the highest frequency seen in MF59-primed volunteers.

The average frequency of such cells was 12% in MF59-primed volunteers, compared with 3.55% in those who were primed without the adjuvant and 2.44 in those who were not primed at all.

Antibody responses were also higher in volunteers who were primed with the adjuvanted vaccine and after six months, high titers of cross-reactive antibody remained detectable among those participants.

The researchers concluded that “distant priming” with the clade 0-like H5N3 induced a pool of memory B cells that could be quickly boosted years later by an adjuvanted vaccine — even if that vaccine had a mismatched strain — to generate high titers of cross-reactive neutralizing antibodies.

“This means that we could vaccinate people potentially many years before a pandemic, to generate memory cells that are long lasting and can be rapidly boosted by a single dose of vaccine when needed,” Dr. Stephenson said in a statement.

The study was supported by Novartis Vaccines and Diagnostics. Dr. Stephenson reported financial links with Novartis and several of the authors are employees of the company.

Primary source: Proceedings of the National Academy of Sciences

Source reference:
Gallia G, et al “Cross-reactive long-lasting B-cell memory against influenza H5N1 after MF59 adjuvanted vaccine: A clinical pre-pandemic vaccine approach” PNAS 2009; DOI: 10.1073/pnas.0903181106.

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• ‘Prime-Boost’ Strategy Might Overcome Avian Flu Vaccine Shortage
  

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