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Background. In the United States (US) the 2014–2015 influenza season was severe, with widespread circulation of influenza A (H3N2) viruses that were antigenically drifted from the vaccine virus. We assessed influenza vaccine effectiveness (VE) against influenza illness requiring hospitalization during the 2014–2015 season; low VE was anticipated due to circulation of drifted viruses.  Method. Adults hospitalized at two hospitals in Southeast Michigan for treatment of acute respiratory illnesses, broadly defined by admission diagnoses, of ≤10 days duration were prospectively enrolled. Throat and nasal swab specimens were collected, combined, and tested for influenza by RT-PCR. Patients were considered vaccinated if receipt of influenza vaccine ≥14 days prior to illness onset was documented in medical records or state registry, or self-reported at enrollment with plausible location and timing of vaccination. VE was estimated by comparing the vaccination status of those who tested positive for influenza with those who tested negative and calculated as 100 × (1-odds ratio) in logistic regression models; models were adjusted for age, sex, hospital, calendar time, time from illness onset to specimen collection, frailty score, and Charlson Comorbidity Index (CCI).  Result. Among 642 patients included in the analysis, 430 (67%) were considered vaccinated, 345 (54%) were female, 228 (36%) were age ≥65 years, and 92% had CCI > 0 indicating ≥1 comorbid condition. One hundred sixteen (18%) patients tested positive for influenza, including 98 (84%) influenza A (H3N2), 9 (8%) influenza A that was not subtyped, and 9 (8%) influenza B Yamagata; 88% of influenza A (H3N2) viruses tested by pyrosequencing belonged to the drifted 3C.2a genetic group. Adjusted VE was 45% (95% CI: 10 to 67) against all influenza, 44% (95% CI: 4 to 68) against A(H3N2) and 82% (95% CI: −7 to 97) against B Yamagata. Adjusted VE against all influenza was 41% (95% CI: −6 to 67) for those <65 years of age and 56% (95% CI: −11 to 83) for those ≥65.  Conclusion. VE estimates appear higher than interim reports from US studies in ambulatory care settings in a year with mismatched vaccine and circulating viruses. Influenza vaccine may have been more effective in preventing severe illness requiring hospitalization; sensitivity analyses are in progress to assess the robustness of estimates.  Disclosures. S. E. Ohmit, Sanofi Pasteur: Grant Investigator, Research grant; E. T. Martin, Pfizer: Grant Investigator, Grant recipient; L. Lamerato, pfizer: Investigator, Research support

Influenza Vaccine Effectiveness Against Antigenically Drifted Influenza Higher Than Expected in Hospitalized Adults: 2014–2015