Progressing toward a universal flu vaccine

U.S. scientists are reporting they have made progress in the search for what’s called the Holy Grail of influenza research — a universal flu vaccine.

TORONTO — U.S. scientists are reporting they have made progress in the search for what’s called the Holy Grail of influenza research — a universal flu vaccine.

In a study published Thursday in the journal Science, they showed that a two-step vaccination process they developed protected mice, ferrets and monkeys against a broad range of flu viruses.

The process triggered development of antibodies that were protective against H1N1 flu viruses dating from 1934 to 2009 — an extraordinary range that could not be matched by conventional flu vaccine.

“I think the way I look at the paper is that it’s a proof of concept study for the idea of a universal vaccine,” said senior author Dr. Gary Nabel, director of the vaccine research centre at the U.S. National Institute of Allergy and Infectious Diseases.

“I think that if you apply what we’ve learned from this, you can certainly generate the kind of multi-valent vaccine” — covering multiple viruses — “that would give you the type of breadth that we would hope to see in a universal vaccine.”

Nabel said that if the work continues in a positive vein, a trial to test the vaccine combination’s efficacy in people might get off the ground in about three years.

Experts concur that finding better flu vaccines is critical because the current process takes too long and is too hit and miss.

“This has got to be the future of influenza vaccine and the fact that groups like this are doing this work is very encouraging,” said Dr. Michael Osterholm, director of the Center for Infectious Diseases Research and Policy at the University of Minnesota.

Osterholm, who was not involved in this research, said the failure to make enough H1N1 vaccine in time to vaccinate before the second wave of last year’s pandemic underscores the limitations of the existing process.

“The vaccine is decades behind the current technology we have,” he said. “This study provides another proof of concept that we can make a 21st-century vaccine that can do it better, faster and for more people.”

Traditional flu vaccine targets a part of the virus that evolves constantly, which is why flu shots are updated virtually annually. The target is the head of the hemagglutinin, the spiky protein on the exterior of the virus that attaches to and invades cells in the respiratory tract.

All flu viruses have a hemagglutinin. But the shape of the protein varies from subtype to subtype.

H1N1’s looks different from that of H3N2. And even within a subtype — the H1 viruses, for instance — the shape changes over time as the virus tries to evade immune systems that have seen earlier viruses from that family.

So a vaccine made to protect against viruses in 2006 might offer some protection against viruses from years just before and just after, but would never be expected to protect against viruses from a decade later or decades earlier.

However, last year another group of researchers in the U.S. reported finding a portion of the hemagglutinin that is what science calls “conserved” — unchanged from virus to virus. It is on a region of the protein that is called the stalk or stem.

In fact, it appears that there are two types of these stems, one for Group 1 flu viruses (including H1, H2 and H5 viruses) and one for Group 2 viruses (including H3 viruses).

Those researchers said they had found antibodies that specifically target the hemagglutinin stalk. But the challenge remained to develop a vaccine that would prompt the immune system to make enough of those antibodies so that it could protect against all Group 1 or all Group 2 viruses.

“We knew that such antibodies could be made. The real question is: Is it possible to elicit them by vaccination?” Nabel said.

His team did that, using two different vaccines. The first, to “prime” the immune system, was a vaccine made up of hemagglutinin DNA from a 1999 H1N1 virus. That was followed up with traditional 1999 flu vaccine (made with killed virus) that was given as a “booster” shot.

Mice were vaccinated with the primer-booster combination and then exposed to what should have been a fatal dose of H1N1 virus from 1934. Nabel said 80 per cent of the mice that received the vaccines survived; all the mice that weren’t vaccinated died.

The work was also done in ferrets and monkeys, though there the scientists were measuring how much virus there was in vaccinated animals’ respiratory tracts after they were exposed to virus. (H1N1 virus would not be fatal to these animals.) They saw substantial reduction in the viral load in the vaccinated animals when they were exposed to 1934 and 2007 viruses.

Nabel said the vaccine combination prepared to protect against H1N1 also neutralized other Group 1 flu viruses like H2N2 and H5N1.

A vaccine combination made with an H3N2 virus didn’t produce antibodies that neutralized Group 1 viruses, but it did protect against a range of H3 viruses.

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