Gran'pop has a touch of the fluWe know that we need to make new vaccines against influenza each year, because new flu strains arise and spread each year and the previous year’s vaccines don’t give protection against the new strains.  Of course, there’s intense research toward developing cross-protective vaccines.  Ideally, flu vaccines would work like measles vaccines — get a shot as a child, be protected throughout life. That may not be a practical goal, but it’s a theoretical target.  More practically, even being able to vaccinate every five years or so would be a big step forward.    It’s clearly not going to be easy, though.  Natural infections don’t particularly offer a lot of cross-protection, and it’s hard1 to get vaccines that induce a stronger immune response than the natural infection.

The pandemic H1N1 influenza last year was an interesting test ground to see how much, if any, cross-protection seasonal influenza vaccines gave.  Unfortunately the results have been pretty confusing, with different studies finding some cross-protection, no cross-protection, or even some increased risk.

The increased risk thing has been hashed out quite extensively already, so if you follow flu stories much you’ve undoubtedly already seen it. This is from the Canadian study2 that found  that people vaccinated against flu in previous years –that is, against different flu strains — were somewhat more likely to get severe flu.

Influenza gargleNo one understands that finding, I think.  (The article itself is open-source, and there’s an excellent commentary on it3 here that’s also open-source, so check it out yourself.)  No one has been able to find any concrete problem with the study, other than its general nature — observational rather than randomized case/control.   But it’s clearly an outlier: Other studies looking at the same thing either find no effect either way, or a modest protective effect.

The latest in the series is a US Army study4 (open source, you can read it yourself) that finds a moderate protective effect of previous flu vaccinations against the pandemic H1N1 (pH1N1):

Our data also suggests that prior receipt of TIV [trivalent inactivated vaccine: IY] or LAIV [live attenuated influenza vaccine: IY] induces an association of protection against pH1N1-associated illness. This may reflect “priming” of the humoral immune system with influenza vaccine as demonstrated in immunologically-naïve children. … Additional findings from our study support the notion that vaccination with seasonal influenza vaccines in the preceding four years (2004–08) also conferred a certain degree of protective immunological memory relevant to the new viral strain. … Thus, it is reasonable to think that CMI [cell-mediated immunity: IY] plays a significant role and that cross-protective CMI to pH1N1 virus may actually exist in individuals who have been frequently immunized and/or exposed to seasonal influenza. 4

You always need to be a little cautious extrapolating army findings like this to the rest of the population. Military populations tend to be more crowded, more stressed, younger, fitter, and more homogeneous than the rest of the population. The vaccination rate among the service members in this study, for example, was much higher than in the general population.  There are a number of other possible sources of confusion that the authors carefully list. And of course, this is again an observational study, not a randomized prospective one.

But in the big picture, it (and similar studies) really do suggest that some cross-protection is possible in a natural population.  That’s really encouraging, because it shows there’s at least a foundation to build on for broadly cross-reactive vaccines.

  1. Though not impossible[]
  2. Skowronski, D., De Serres, G., Crowcroft, N., Janjua, N., Boulianne, N., Hottes, T., Rosella, L., Dickinson, J., Gilca, R., Sethi, P., Ouhoummane, N., Willison, D., Rouleau, I., Petric, M., Fonseca, K., Drews, S., Rebbapragada, A., Charest, H., Hamelin, M., Boivin, G., Gardy, J., Li, Y., Kwindt, T., Patrick, D., Brunham, R., & , . (2010). Association between the 2008–09 Seasonal Influenza Vaccine and Pandemic H1N1 Illness during Spring–Summer 2009: Four Observational Studies from Canada PLoS Medicine, 7 (4) DOI: 10.1371/journal.pmed.1000258[]
  3. Viboud, C., & Simonsen, L. (2010). Does Seasonal Influenza Vaccination Increase the Risk of Illness with the 2009 A/H1N1 Pandemic Virus? PLoS Medicine, 7 (4) DOI: 10.1371/journal.pmed.1000259[]
  4. Johns, M., Eick, A., Blazes, D., Lee, S., Perdue, C., Lipnick, R., Vest, K., Russell, K., DeFraites, R., & Sanchez, J. (2010). Seasonal Influenza Vaccine and Protection against Pandemic (H1N1) 2009-Associated Illness among US Military Personnel PLoS ONE, 5 (5) DOI: 10.1371/journal.pone.0010722[][]