CDC investigators believe they have determined the cause for influenza vaccine effectiveness decline.
There are intra-seasonal decreases in measured vaccine effectiveness (mVE) for the influenza vaccine, according to a paper published in Clinical Infectious Diseases.
Investigators from the US Centers for Disease Control and Prevention (CDC) estimated daily numbers of flu vaccines from the 2011-12 season to the 2014-15 season in order to determine the contribution of “leaky” vaccines to the observed decline of mVE. “Leaky” vaccines are those that provide partial protection in all vaccinated patients rather than complete protection in some vaccinated patients. Leaky vaccines contribute to mVE, as do risk measures that include prior cases in risk denominators, the study authors explained.
Every time mVE declines by -13%, infection risk is reduced by half to 25% among vaccinated patients with leaky vaccines, the study authors added.
The simulation included 4 age groups (9-17 years; 18-49 years; 50-64 years; 65+ years) and the investigators found a total infection rate between 15-31% for each season. They calculated the mVE separately for each virus: H1N1, H3N2, and B and classified “patients” as vaccinated and unvaccinated, though some may have received a vaccine later the day of their inclusion in the simulation.
The study authors conducted their simulations the first time under the parameters that there were no re-infections in a given season, though reinfections during a season would reinforce their results with a leaky vaccine. Their baseline simulation allowed for a 25% infection rate, 50% vaccination coverage, and 50% vaccine effectiveness.
mVE remained stable at 50% during the first simulation, the study authors reported, but it dropped to 41% for the leaky mechanism. mVE was strongly related to seasonal infection when the infection rate was 12.5%, the study authors found. In all of the simulations the investigators conducted, declines in mVE were greater for the leaky than for the variable mechanism, they said.
When testing the effects of varying total infection rate (between 15-31%) for all ages and seasons, the higher infection rates were associated with greater decreases in mVE, the study authors determined. Among leaky vaccines with no reinfections for H1N1, mVE was -4.6% for the higher vs. -1.7% for the lower rate, they said. This was consistent and similar for the H3N2 and B viruses when simulated.
The study ultimately identified key parameters that can impact mVE associated with the leaky vaccine mechanism, most importantly infection rate, the investigators said. Total infection rate had the greatest effect on declining mVE, for both symptomatic and asymptomatic cases.
In a model the investigators ran where vaccinated patients experienced a varying vaccine effect, mVE declined similarly to the leaky mechanism. A variable mechanism seemed more biologically plausible in this case, the study authors said, but a leaky mechanism is easier computationally and produces the maximum estimate for mVE decrease.
“While it is not known whether the influenza vaccine mechanism is leaky, the possibility that leaky
vaccine effect could account for observed decreases in mVE creates uncertainty,” the study authors concluded. “Our simulations suggest that a leaky vaccine mechanism would likely account for only some of the observed decline in mVE.”
They noted that the CDC recommends that flu vaccination be administered before the end of October, however, the study authors believe their findings open the possibility of delaying vaccination until the fall when a vaccine with higher VE may be produced and offer more protection.
“Our results underscore the need to better understand factors contributing to and devise strategies to deal with intra-seasonal VE decline,” they wrote.