Influenza Vaccine Effectiveness in the United States during the 2015–2016 Season

Abstract

BACKGROUND The A(H1N1)pdm09 virus strain used in the live attenuated influenza vaccine was changed for the 2015–2016 influenza season because of its lack of effectiveness in young children in 2013–2014. The Influenza Vaccine Effectiveness Network evaluated the effect of this change as part of its estimates of influenza vaccine effectiveness in 2015–2016. METHODS We enrolled patients 6 months of age or older who presented with acute respiratory illness at ambulatory care clinics in geographically diverse U.S. sites. Using a test-negative design, we estimated vaccine effectiveness as (1 – OR) × 100, in which OR is the odds ratio for testing positive for influenza virus among vaccinated versus unvaccinated participants. Separate estimates were calculated for the inactivated vaccines and the live attenuated vaccine. RESULTS Among 6879 eligible participants, 1309 (19%) tested positive for influenza virus, predominantly for A(H1N1)pdm09 (11%) and influenza B (7%). The effectiveness of the influenza vaccine against any influenza illness was 48% (95% confidence interval [CI], 41 to 55; P<0.001). Among children 2 to 17 years of age, the inactivated influenza vaccine was 60% effective (95% CI, 47 to 70; P<0.001), and the live attenuated vaccine was not observed to be effective (vaccine effectiveness, 5%; 95% CI, −47 to 39; P = 0.80). Vaccine effectiveness against A(H1N1)pdm09 among children was 63% (95% CI, 45 to 75; P<0.001) for the inactivated vaccine, as compared with −19% (95% CI, −113 to 33; P = 0.55) for the live attenuated vaccine. CONCLUSIONS Influenza vaccines reduced the risk of influenza illness in 2015–2016. However, the live attenuated vaccine was found to be ineffective among children in a year with substantial inactivated vaccine effectiveness. Because the 2016–2017 A(H1N1)pdm09 strain used in the live attenuated vaccine was unchanged from 2015–2016, the Advisory Committee on Immunization Practices made an interim recommendation not to use the live attenuated influenza vaccine for the 2016–2017 influenza season. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health.)

Differential gene expression elicited by children in response to the 2015–16 live attenuated versus inactivated influenza vaccine

“…The dramatic difference between transcriptomic responses to the two vaccines and previous findings that children who received LAIV generated a less robust IgG antibody response than those who received IIV [8] provide new insights to help explain the lower vaccine effectiveness of LAIV observed during the 2015–16 influenza season [7]. Cao et al, found differential expression in the IIV group of plasma cell-mediated and inflammation genes, but in the LAIV group found IFN and cell-cycle-related transcripts [11].…”

“…Certain IFN-related DEGs were also correlated with antibody response. We add to this important work of Cao et al, by including a larger sample size of children using data from the last season that LAIV was widely used and a season when LAIV did not perform well, as reported by the US Flu VE Network [7]. …”

“…The reason for the reported decline in LAIV VE from previous seasons [3, 4] is unclear. Initially believed to be due to heat instability of the A/H1N1 construct in 2014–2015 [5, 6], manufacturer’s modifications of the vaccine did not improve VE in 2015–2016 season [7]. In response to this low VE, the Advisory Committee on Immunization Practices does not currently support the use of LAIV, thereby removing the intranasal delivery mechanism preferred by many children.…”

Burden of medically attended influenza infection and cases averted by vaccination – United States, 2013/14 through 2015/16 influenza seasons

“…[12] Subjects were classified according to age on September 1 st of each season (6 months to 8 years; 9 to 17 years; 18 to 49 years, 50 to 64 years; and 65 years or older) and receipt of current season’s influenza vaccine, as defined from administrative healthcare databases and state immunization registries. [15] We identified all ambulatory care visits for presumptive medically attended acute respiratory illness (ARI) based on International Classification of Diseases, Version 9, Clinical Modification (ICD-9, for encounters prior to 1 October 2014) and Version 10 (ICD-10, for encounters on or after 1 October 2014) codes (Supplemental Appendix). …”

Functional growth inhibition of influenza A and B viruses by liquid and powder components of leaves from the subtropical plant Melia azedarach L.

“…H1N1, H3N2, and B influenza viruses, trivalent vaccines have been established to combat A (H1N1) pdm 09, H3N2 subtype, and B viruses [1]. Despite major vaccination efforts, antigenic variation occurring in epidemic seasons frequently reduces the efficacy of seasonal inactivated or live vaccines in Japan and the United States of America (USA) [2, 3]. For example, although 100% of children in primary and junior high schools in the southwestern region of Japan are vaccinated, large outbreaks have occurred in these schools, indicating that influenza virus variants quite different from the vaccine strains are prevalent in this area during the spring season [2].…”