Control of influenza through vaccination is a particularly difficult task because of the continued antigenic evolution of influenza viruses.
Influenza viruses rapidly accumulate mutations… that allow them to escape from immunity generated by prior vaccination or infection, a process known as “antigenic drift.”
One consequence of this phenomenon is that for optimal protection, the viruses contained in the vaccine should match the virus(es) causing the outbreaks as closely as possible, requiring comprehensive surveillance for new emerging variants, and continuous updating of the vaccine.
Multiple large networks have been established in the United States, Canada, Europe, and other countries to monitor the effectiveness of influenza vaccine on a yearly basis…
[I]ndividuals with acute respiratory illness are assessed, and the vaccination history of subjects with laboratory-documented influenza (test-positive cases) is com- pared to that of those whose tests were negative (test-negative controls).
Over the last several years, many of these studies have suggested that vaccination in prior seasons can reduce the effectiveness of vaccination in the current season…
The mechanisms that might be responsible for a negative effect of prior vaccination on vaccine effectiveness are not known, but are reviewed in detail in the article.
[A] person who has not been previously vaccinated might mount a broader response…
Other potential mechanisms could include interference by prior immunity on antigenic presentation, or the “infection-block hypothesis.” In this case, prior vaccination reduces prior infections with influenza virus, which in turn would have provided more effective protection against subsequent drifted influenza infection than the vaccine does, resulting in lower rates of influenza in subjects with infection-based immunity than in those with vaccine-induced immunity.
In one year of the study, it appeared that multiply vaccinated subjects were actually more likely to develop influenza than unvaccinated subjects (that is, VE was statistically significantly less than zero).
A similar effect was noted during the 2009 influenza A virus subtype H1N1 pandemic when increased rates of pandemic H1N1 were reported in patients who had previously received seasonal H1N1 vaccine in Canada…
The authors speculate that this might be consistent with a disease-enhancing effect of influenza vaccine.
Vaccine-enhanced disease has been recognized as a potential problem in other human infectious diseases such as dengue, and respiratory syncytial virus, and can be a significant obstacle to vaccine development.
There is relatively little evidence to support any form of enhanced influenza disease in humans, although disease enhancement… was reported in the 2009 pandemic.
Measurements of disease severity were not reported in the current study, so it is not possible to judge whether the disease was more severe in multiply vaccinated individuals.
Because there is no current practical alternative to annual vaccination… [public health recommendations] will probably not change…