Intraseason waning of influenza vaccine protection: Evidence from the US Influenza Vaccine Effectiveness Network, 2011-12 through 2014-15.

Background:Recent studies suggest that influenza vaccine effectiveness (VE) may wane over the course of an influenza season, leading to suboptimal VE during late influenza seasons. Methods:We examined the association between influenza VE and time since vaccination among patients ≥9 years old with medically-attended acute respiratory illness in the US Influenza Vaccine Effectiveness Network using data pooled from the 2011-12 through 2014-15 influenza seasons. We used multivariate logistic regression with PCR-confirmed influenza infection as the outcome and vaccination status defined by days between vaccination and symptom onset as the predictor. Models were adjusted for calendar time and other potential confounding factors. Results:We observed decreasing VE with increasing time since vaccination for influenza A(H3N2) (p=0.004), influenza A(H1N1)pdm09 (p=0.01), and influenza B viruses (p=0.04). Maximum VE was observed shortly after vaccination, followed by a decline in VE of about 7% (absolute) per month for influenza A(H3N2) and influenza B and 6% - 11% per month for influenza A(H1N1)pdm09 viruses. VE remained greater than zero for at least six months for influenza A(H1N1)pdm09 and influenza B and at least five months for influenza A(H3N2) viruses. Decline in VE was more pronounced among patients with prior season influenza vaccination. A similar pattern of increasing influenza risk with increasing time since vaccination was seen in analyses limited to vaccinees. Conclusions:We observed decreasing influenza vaccine protection with increasing time since vaccination across influenza types/subtypes. This association is consistent with intraseason waning of host immunity, but bias or residual confounding could explain these findings.