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Background. During the 2012–2013 influenza season, there was cocirculation of influenza A(H3N2) and 2 influenza B lineage viruses in the United States.Methods. Patients with acute cough illness for ≤7 days were prospectively enrolled and had swab samples obtained at outpatient clinics in 5 states. Influenza vaccination dates were confirmed by medical records. The vaccine effectiveness (VE) was estimated as [100% × (1 − adjusted odds ratio)] for vaccination in cases versus test-negative controls.Results. Influenza was detected in 2307 of 6452 patients (36%); 1292 (56%) had influenza A(H3N2), 582 (25%) had influenza B/Yamagata, and 303 (13%) had influenza B/Victoria. VE was 49% (95% confidence interval [CI], 43%–55%) overall, 39% (95% CI, 29%–47%) against influenza A(H3N2), 66% (95% CI, 58%–73%) against influenza B/Yamagata (vaccine lineage), and 51% (95% CI, 36%–63%) against influenza B/Victoria. VE against influenza A(H3N2) was highest among persons aged 50–64 years (52%; 95% CI, 33%–65%) and persons aged 6 months–8 years (51%; 95% CI, 32%–64%) and lowest among persons aged ≥65 years (11%; 95% CI, −41% to 43%). In younger age groups, there was evidence of residual protection from receipt of the 2011–2012 vaccine 1 year earlier.Conclusions. The 2012–2013 vaccines were moderately effective in most age groups. Cross-lineage protection and residual effects from prior vaccination were observed and warrant further investigation.

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The effect of prior influenza vaccination history on vaccine effectiveness was assessed in a community cohort over 8 seasons. Current- and previous-season vaccination generated similar levels of protection; vaccine-induced protection was greatest for individuals with no recent vaccination history.

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.)

Background. Circulating A/H3N2 influenza viruses drifted significantly after strain selection for the 2014-2015 vaccines. Also in 2014-2015, the Advisory Committee on Immunization Practices recommended preferential use of live attenuated influenza vaccine (LAIV) over inactivated influenza vaccine (IIV) among children aged 2-8 years.Methods. Vaccine effectiveness (VE) across age groups and vaccine types was examined among outpatients with acute respiratory illness at 5 US sites using a test-negative design, that compared the odds of vaccination among reverse transcription polymerase chain reaction-confirmed influenza positives and negatives.Results. Of 9311 enrollees with complete data, 7078 (76%) were influenza negative, 1840 (19.8%) were positive for influenza A (A/H3N2, n = 1817), and 395 (4.2%) were positive for influenza B (B/Yamagata, n = 340). The overall adjusted VE was 19% (95% confidence interval [CI], 10% to 27%) and was statistically significant in all age strata except those aged 18-64 years. The adjusted VE of 6% (95%CI, −5% to 17%) against A/H3N2-associated illness was not statistically significant, unlike VE for influenza B/Yamagata, which was 55% (95%CI, 43% to 65%). Among those aged 2-8 years, VE against A/H3N2 was 15% (95%CI, −16% to 38%) for IIV and −3% (CI, −50% to 29%) for LAIV; VE against B/Yamagata was 40% (95%CI, −20% to 70%) for IIV and 74% (95%CI, 25% to 91%) for LAIV.Conclusions. The 2014-2015 influenza vaccines offered little protection against the predominant influenza A/H3N2 virus but were effective against influenza B. Preferential use of LAIV among young children was not supported.

Introduction: Studies in the 1970s and 1980s signaled concern that repeated influenza vaccination could affect vaccine protection. The antigenic distance hypothesis provided a theoretical framework to explain variability in repeat vaccination effects based on antigenic similarity between successive vaccine components and the epidemic strain. Areas covered: A meta-analysis of vaccine effectiveness studies from 2010-11 through 2014-15 shows substantial heterogeneity in repeat vaccination effects within and between seasons and subtypes. When negative effects were observed, they were most pronounced for H3N2, especially in 2014-15 when vaccine components were unchanged and antigenically distinct from the epidemic strain. Studies of repeated vaccination across multiple seasons suggest that vaccine effectiveness may be influenced by more than one prior season. In immunogenicity studies, repeated vaccination blunts the hemagglutinin antibody response, particularly for H3N2. Expert commentary: Substantial heterogeneity in repeated vaccination effects is not surprising given the variation in study populations and seasons, and the variable effects of antigenic distance and immunological landscape in different age groups and populations. Caution is required in the interpretation of pooled results across multiple seasons, since this can mask important variation in repeat vaccination effects between seasons. Multi-season clinical studies are needed to understand repeat vaccination effects and guide recommendations. ARTICLE HISTORY

During 2013-2014, IIV was significantly effective against A(H1N1)pdm09. Lack of LAIV4 effectiveness in children highlights the importance of continued annual monitoring of effectiveness of influenza vaccines in the United States.