Influenza vaccine's efficacy far from perfect

There are substantial gaps in the evidence supporting the effectiveness of influenza vaccines, particularly in the elderly, according to the findings of large systematic review and meta-analysis.

Although the published report highlights the death of data that support influenza vaccine, it should not be interpreted as a suggestion to stop vaccinating, the study’s lead author and director of the center for infectious disease research and policy at the University of Minnesota, Minneapolis said.

His intent in conducting and publishing this analysis was not to cast doubt on current influenza immunization efforts, but rather to influence the pace of new vaccine development. “There is a major barrier to entry right now for venture capital and start-up companies to bring new novel technologies forward. When you have a vaccine that’s universally recommended, said by public health to be effective, and is quite cheap, why would anybody spend a billion-dollars to try to make a new vaccine that’s going to be much more expensive?”

Of a total 5,707 studies published from 1967 through Feb. 15, 2011, just 31 (17 randomized and 14 observational studies) met a list of strict criteria, the most salient being the use of influenza confirmed by culture or real-time polymerase chain reaction as an outcome.

“Efficacy” was defined as the reduction in influenza risk assessed from randomized clinical trials, whereas vaccine “effectiveness” was determined in observational, “real-world” trials.

The analysis included studies of both the trivalent inactivated vaccine (TIV) and the live attenuated (intranasal) influenza vaccine (LAIV). Among the 10 randomized, controlled trials of TIV over 12 influenza seasons, analyses for 8 of the seasons showed significant efficacy, whereas 4 did not. Of eight studies that were conducted in healthy adults aged 18-64 years over a total of nine flu seasons, the pooled efficacy was 59%. One study conducted in children aged 6-24 months over two flu seasons produced dramatically different efficacy results: 66% in the first year, -7% in the next. The “minus” essentially means zero, rather than suggesting an increased risk from the vaccine.

No randomized, controlled trials met the criteria for children, aged 2-17 years, or for adults aged 65 years and older. Indeed, conducting placebo-controlled trials in adults aged 65 and older would be considered unethical because influenza vaccine has been recommended for that age group since 1960.

The picture for LAIV was different: Of the 10 randomized controlled trials assessing LAIV efficacy during 12 flu seasons, 9 showed significant efficacy. All of these were done in healthy individuals. In children aged 6 months to 7 years, there were six studies covering eight influenza seasons. The vaccine was effective in all eight, with a pooled efficacy of 83%.

But LAIV data in other age groups were less impressive. One study of LAIV in adults aged 60 and older showed significant overall efficacy (42%), but — oddly — efficacy was lower in those aged 60-69 years and higher in those aged 70 and older.

Of three randomized, controlled trials of LAIV in adults aged 18-49, none showed significant protection, and no such trials met the inclusion criteria for children aged 8-17 years.

Vaccine effectiveness varied in the nine observational trials of seasonal flu vaccine, with 6 of 17 embedded analyses showing significant protection against medical-attended, laboratory-confirmed influenza. The proportion of patients receiving TIV or LAIV was not explicit stated for these studies, but based on the age and license use, most estimates were for TIV. Of the five observational studies that assessed effectiveness of the 2009 pandemic H1N1 vaccine, Median efficacy was 69% (range, 60%-93%).