Flu shot mismatched on B virus, early data suggests

It appears there may be a partial flu shot mismatch again this year, with early data from Canada, the United States and Britain suggesting the vaccine component meant to protect against influenza B is not a match for the flu B viruses causing the most disease.

Predicting which family of influenza B viruses will dominate in a coming year — and therefore should be covered by the flu shot — is a challenge that has defied the experts in five of the last seven flu seasons, at least so far as disease patterns in North America are concerned.

The ongoing problem has prompted exploration of the idea that flu shots should be reformulated to add a second B component to a vaccine that currently protects against one family of B viruses and the two influenza A subtypes, H3N2 and H1N1.

Scientists from the U.S. Centers of Disease Control are working on a cost-benefit analysis of just such a move and are to meet Monday to begin going over the pros and cons. They plan to present their findings sometime next month to the Food and Drug Administration, which regulates vaccines in the United States.

"Historically, it's obviously been difficult to predict which one's coming next," Dr. Joseph Bresee, the CDC's chief of influenza surveillance and prevention, says of the flu B viruses.

"And so one way to hedge those bets is just put them both in the vaccine."

Whether vaccine manufacturers would welcome the added task is unclear. Because influenza viruses mutate so rapidly, flu shots are reformulated almost every year. Manufacturers could argue that adding a fourth component to an already complex task might cause more problems than it fixes.

Bresee admits the CDC analysis suggests the answer isn't clear cut. "If you look at it, it's more complicated than you'd think."

Until about eight years ago, only one family or lineage of B viruses circulated globally at one time. But in 2001 a second emerged from Asia and the two — known as B/Yamagata and B/Victoria — have co-circulated since. Each year one or the other has been dominant, though there is no clear pattern of how or when they alternate.

Because the viruses are from distinct lineages, it is thought vaccine made to protect against viruses from one would offer little or no protection against viruses from the other. However, ongoing Canadian vaccine effectiveness studies show that isn't always the case.

"All is not lost if there is that lineage level mismatch, because in the seasons that we have monitored it, we have — at least so far — shown that there has been some cross protection," says Dr. Danuta Skowronski, a flu expert with the British Columbia Centre for Disease Control.

Some years that cross protection can be reasonably high, though Skowronski admits other years mismatched B vaccine appears to offer little protection to the people who get it.

This year's flu vaccine was designed to protect against B/Yamagata viruses. But in Canada, the U.S. and Britain so far this season, B/Victoria viruses have been responsible for a majority of confirmed flu B cases. It is still early in the season, though, and  patterns could still change.

"I think it's way too early to tell," says Bresee when asked if the B component of the vaccine is mismatched.

Even if there is a mismatch, it may not matter too much in the United States and Britain.

Influenza A viruses like H3N2 have dominated in Britain's raging flu season; flu B has been a bit player there so far. And in the United States, H1N1 viruses have to date been the major source of disease.

The H3N2 and H1N1 components of this year's flu shot are well matched to circulating viruses.

But in Canada, where flu activity is just starting to pick up, B viruses have made up the bulk of confirmed cases so far — making a vaccine mismatch potentially more problematic here.

"The activity is I think beginning and it's looking like it's mostly B at the moment — although you know it's still a shade early to be sure, I think," says Dr. Allison McGeer, an infectious diseases expert at Toronto's Mount Sinai Hospital.

"And the majority of B isolates so far have been mismatched.... So it's probably true that there's going to be a B mismatch."

If that trend continues to hold, there are some mitigating factors.

Influenza B viruses typically cause less severe illness than influenza A viruses. And unlike the H1N1 viruses, B viruses have not developed resistance to the antiviral drug Tamiflu.

So if it is clear Canada is having a flu B season, doctors treating seriously ill flu patients should have a reasonable expectation that the drug will work, McGeer says.

As for whether or not the flu shot should contain two B components, McGeer thinks it's an idea whose time may have come.

"We're … going to have to try to deal with the fact that we've now got these two lineages and they look like they're staying. It would be very helpful to know what the right thing to do is," she says.

But Bresee sounds unsure whether the benefits — fewer people catching flu B and fewer people hospitalized because of it — will in the end outweigh the added challenge for manufacturers and the added cost.

"It's easy for us to do the science and do the models. And it's easy for us to give an opinion about the relative health benefits. What I don't know is our FDA partners, our industry partners — what these data mean for them," he admits.

"Whether a good idea meets with practical considerations that make it impossible, I don't know."