Several observational studies have shown decreases in measured influenza vaccine effectiveness (mVE) during influenza seasons. One study found decreases of 6%-11% per month during the 2011-12 to 2014-15 seasons. These findings could indicate waning immunity but could also occur if vaccine effectiveness is stable and vaccine provides partial protection in all vaccinees ("leaky") rather than complete protection in a subset of vaccinees. Since it is not known whether influenza vaccine is leaky, we simulated the 2011-12 to 2014-15 influenza seasons to estimate the potential contribution of leaky vaccine effect to the observed decline in mVE.
We used available data to estimate daily numbers of vaccinations and infections with A/H1N1, A/H3N2 and B viruses. We assumed that vaccine effect was leaky, calculated mVE as 1 minus the Mantel-Haenszel relative risk of vaccine on incident cases and determined the mean mVE change per 30 days since vaccination. Because change in mVE was highly dependent on infection rates, we performed simulations using low (15%) and high (31%) total (including symptomatic and asymptomatic) seasonal infection rates.
For the low infection rate, decreases (absolute) in mVE per 30 days after vaccination were 2% for A/H1N1 and 1% for A/H3N2and B viruses. For high infection rate, decreases were 5% for A/H1N1, 4% for A/H3, and 3% for B viruses.
The leaky vaccine bias could account for some, but probably not all of the observed intra-seasonal decreases in mVE. These results underscore the need for strategies to deal with intra-seasonal vaccine effectiveness decline.