Individual Patient-Level Data Meta-Analysis of Live Attenuated and Inactivated Influenza Vaccine Effectiveness among US Children, 2013-14 through 2015-16

Background: Quadrivalent live attenuated influenza vaccine (LAIV4) was not recommended for use in the United States for the 2016-17 and 2017-18 influenza seasons based on US observational studies of vaccine effectiveness (VE) from 2013-14 to 2015-16.  We pooled individual patient data on children aged 2–17 years enrolled in 5 US studies during these 3 influenza seasons to further investigate VE by vaccine type.

Methods: Analyses included 17,173 children enrolled in the US Department of Defense Global Laboratory-based Influenza Surveillance Program, US Influenza Vaccine Effectiveness Network, Influenza Incidence Surveillance Project, Influenza Clinical Investigation for Children, and a Louisiana State University study.  Participants’ specimens were tested for influenza by reverse transcription-polymerase chain reaction (RT-PCR), culture, or a combination of rapid antigen testing and RT-PCR.  VE was calculated by comparing odds of vaccination with either inactivated influenza vaccine (IIV) or LAIV4 among influenza-positive cases to test-negative controls and calculated as 100 x (1- odds ratio) in logistic regression models with age, calendar time, influenza season and study site (random effect).   Patients were stratified by prior season vaccination status in a sub-analysis.

Results: Overall, 38% of patients (N=6,558) were vaccinated in the current season, of whom 30% (N=1,979) received LAIV4.  Pooled VE of IIV against any influenza virus was 51% (95% CI: 47, 54) versus 26% (95% CI: 15, 36) for LAIV4.  Point estimates for pooled VE against any influenza by age group ranged from 45–58% for IIV and 19–34% for LAIV4 during the 3 seasons (Figures 1, 2).  Pooled VE against influenza A(H1N1)pdm09 was 67% (95% CI: 62, 72) for IIV versus 20% (95% CI: -6, 39) for LAIV4.  Pooled VE against influenza A(H3N2) was 29% (95% CI: 14, 42) for IIV versus 7% (95% CI: -11, 23) for LAIV4, and VE against influenza B was 52% (95% CI: 42, 60) for IIV and 66% (95% CI: 47, 77) for LAIV4.  VE against influenza A(H1N1)pdm09 was lower for LAIV4 versus IIV across all strata of prior season vaccination (Figure 3).

Conclusion: Consistent with individual studies, our pooled analyses found that LAIV4 effectiveness was reduced for all age groups against influenza A(H1N1)pdm09 compared to IIV.  This result did not vary based on prior vaccination status.