Last year, several studies suggested that individuals in Canada who had previously been vaccinated against seasonal influenza faced an increased risk of pandemic H1N1 (pH1N1).

Those studies have undergone further peer review and researchers writing in PLoS Medicine say their conclusions may be valid, though more research needs to be done to confirm the results.

The first of the studies used an ongoing sentinel monitoring system to assess the frequency of prior vaccination with the 2008 seasonal vaccine in people with pH1N1 influenza (cases) compared to people without evidence of infection with an influenza virus (controls). This study confirmed that the seasonal vaccine provided protection against seasonal influenza, but found it to be associated with an increased risk of approximately 68% for pH1N1 disease.

The further 3 studies (which included additional case-control investigations in Ontario and Quebec, as well as a transmission study in 47 Quebec households where pH1N1 influenza had occurred) similarly found between 1.4 and 1.5 times increased likelihood of pH1N1 illness in people who had received the seasonal vaccine compared to those who had not. Prior seasonal vaccination was not associated with an increase in hospitalization among those who developed pH1N1 illness.

If the findings from these studies are real they raise important questions about the biological interactions between pre-existing and novel pandemic influenza strains. The researchers note, however, that the World Health Organization has recommended that pH1N1 be included in subsequent seasonal vaccine formulations. This will provide direct protection against pH1N1 and thereby obviate any risk that might have been due to the seasonal vaccine in 2009, which did not include pH1N1.

Nonetheless, there are plenty of reasons to remain skeptical about the link between seasonal flu vaccines and risk for H1N1. All four studies were observational and, as a result, don't prove a causal relationship. Furthermore, studies conducted in other countries found no relationship between the vaccine and H1N1 susceptibility, or found that the vaccine actually lowered H1N1 risk.

"Given the uncertainty associated with observational studies, we believe it would be premature to conclude that increased the risk of 2009 pandemic illness, especially in light of six other contemporaneous observational studies in civilian populations that have produced highly conflicting results," says an editorial accompanying the new PLoS Medicine study.

: Skowronski et al., 'Association between the 2008–09 Seasonal Influenza Vaccine
and Pandemic H1N1 Illness during Spring–Summer 2009: Four Observational Studies from Canada.', PLoS Med 7(4): e1000258; doi:10.1371/journal.pmed.1000258