Will getting a seasonal vaccine make you more or less likely to get pandemic flu?

Pandemic flu vaccine is not available yet in North America, but seasonal flu vaccine is. Should you get it?

The answer is not clear. There are several facts that are in its favor, and one media story that is strongly against it.

First, the facts in favor of getting the seasonal vaccine.

1. Getting seasonal flu vaccine may protect you against seasonal flu strains. Although H1N1 appears to be the dominant flu strain, the seasonal strains are still circulating at some, apparently low, level. Seasonal flu is no fun to get and can be quite dangerous to people in high risk groups, so getting vaccinated against it makes sense, especially for people at risk of complications from seasonal flu.

2. In an experimental study, ferrets that were exposed to animals infected with both seasonal and pandemic flu were more likely to experience severe symptoms. One of these secondary contacts had to be euthanised. The number of animals involved was small and the mechanism for this phenomenon was not identified, so we don’t know if these results will extrapolate to humans. Still, no-one wants to be a potential source of a virus that causes more severe disease in others. Getting vaccinated against seasonal flu would decrease the probability of this happening.

3. There is limited evidence that vaccination against seasonal flu may provide some protection to some people against pandemic flu. From a study by Hancock et al. in the New England Journal of Medicine:

Vaccination of 344 adults with inactivated seasonal vaccine resulted in seroconversion against the seasonal H1N1 vaccine strain in 65 of 83 adults between the ages of 18 and 40 years (78%), in 111 of 148 of those between the ages of 18 and 64 years (75%), and in 9 of 49 (18%) and 34 of 63 (54%) of those 60 years of age or older, depending on the year (Table 1). Seroconversion to antibodies against 2009 H1N1 was observed in 10 of 83 adults (12%) between the ages of 18 and 40 years, in 33 of 148 adults (22%) between the ages of 18 and 64 years, and in 3 of 63 (5%) or none of 50 adults 60 years of age or older, depending on the year.

Thus, vaccination with a seasonal vaccine resulted in the production of antibodies against pandemic flu in 22% of people between the ages of 18 and 64 years old. It had no significant effect in any other age group. A 22% protection against pandemic flu isn’t much, but it is better than nothing.

Another study provides further support for the idea that seasonal flu vaccines might stimulate antibody production against pandemic flu. From a study by Greenberg et al. also in the New England Journal of Medicine:

At baseline, 76 of 240 subjects (31.7%) had antibody titers of 1:40 or more on hemagglutination-inhibition assay (Table 2 and Figure 2A and 2C), with no significant differences between either age groups (P=0.21) or dose groups (P=0.68). Similarly, there were no significant differences in baseline geometric mean titers (GMTs) between age groups or dose groups (Table 3). Of note, baseline titers of 1:40 or more on hemagglutination-inhibition assay were observed in 48 of 108 subjects who had received the 2009 seasonal vaccine (44.4%; 95% confidence interval [CI], 35.4 to 53.8), as compared with 28 of 132 subjects who had not received the seasonal vaccine (21.2%; 95% CI, 15.1 to 28.9; P<0.001 by Fisher’s exact test).

What this suggests is that 44% of the people who had been vaccinated with seasonal flu vaccine already had antibodies against pandemic flu before they received a vaccine against it. 28% of the people who had *not* been vaccinated against either seasonal or pandemic flu also had antibodies pandemic flu. One explanation for this might be that these people had had seasonal flu at some time in the past and that this had stimulated their immune systems to produce antibodies that happen to cross-react against pandemic flu.

Taken together, the Hancock et al. and Greenberg et al. papers suggest that getting vaccinated against seasonal flu might provide some protection against pandemic flu in about 20% of adults under the age of 65. This is a very modest degree of efficacy, but, on a population basis, could translate to a significant reduction in illness and death.

But now we must consider the argument against getting vaccinated with seasonal flu. There is a single media report, with no explanation of mechanism, suggesting that getting vaccinated with seasonal flu makes people more likely to get pandemic flu. From CBCnews, September 23, 2009:

Preliminary research suggests the seasonal flu shot may put people at greater risk for getting swine flu, CBC News has learned.

“This is some evidence that has been floated. It hasn’t been validated yet, it’s very preliminary,” cautioned Dr. Don Low, microbiologist-in-chief at Mount Sinai Hospital in Toronto.

“This is obviously important data to help guide policy decisions. How can we best protect people against influenza?”

It’s important to validate the information to make sure it’s not just a fluke, and that the observation is confirmed elsewhere such as in the Southern Hemisphere, which just completed its seasonal flu season, Low added.

Four Canadian studies involved about 2,000 people in Ontario, Quebec, British Columbia and Alberta, health officials told CBC News. Researchers found people who had received the seasonal flu vaccine in the past were more likely to get sick with the H1N1 virus.

Without more details, it is impossible to judge the Canadian studies. Ideally, the publication of these studies should have preceded their announcement to the press so that other scientists could give their interpretation of the results. One hopes that the authors will publish a complete description of their work, immediately. Any indication whatsoever that the seasonal flu vaccine increases ones risk of getting pandemic flu will cause large numbers of people who were going to get the vaccine to change their minds.

I had intended to get the seasonal flu vaccine, but had not gotten around to it yet. Now, I will wait and see what I think of the Canadian studies before I get one.

I hope they don’t wait too long to release their results.


Perez et al. (2009) Fitness of Pandemic H1N1 and Seasonal influenza A viruses during Co-infection. PLoS Currents.

Hancock et al. (2009) Cross-Reactive Antibody Responses to the 2009 Pandemic H1N1 Influenza Virus. New England J. Med.

Greenberg et al. (2009) Response after One Dose of a Monovalent Influenza A (H1N1) 2009 Vaccine — Preliminary Report. New England J. Med.


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