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Background RIV4 and cell-culture based inactivated influenza vaccine (ccIIV4) have not been compared to egg-based IIV4 in healthcare personnel, a population with frequent influenza vaccination that may blunt vaccine immune responses over time. We conducted a randomized trial among healthcare personnel (HCP) aged 18–64 years to compare humoral immune responses to ccIIV4 and RIV4 to IIV4. Methods During the 2018–2019 season, participants were randomized to receive ccIIV4, RIV4, or IIV4 and had serum samples collected prevaccination, 1 and 6 months postvaccination. Serum samples were tested by hemagglutination inhibition (HI) for influenza A/H1N1, B/Yamagata, and B/Victoria and microneutralization (MN) for A/H3N2 against cell-grown vaccine reference viruses. Primary outcomes at 1 month were seroconversion rate (SCR), geometric mean titers (GMT), GMT ratio, and mean fold rise (MFR) in the intention-to-treat population. Results In total, 727 participants were included (283 ccIIV4, 202 RIV4, and 242 IIV4). At 1 month, responses to ccIIV4 were similar to IIV4 by SCR, GMT, GMT ratio, and MFR. RIV4 induced higher SCRs, GMTs, and MFRs than IIV4 against A/H1N1, A/H3N2, and B/Yamagata. The GMT ratio of RIV4 to egg-based vaccines was 1.5 (95% confidence interval [CI] 1.2–1.9) for A/H1N1, 3.0 (95% CI: 2.4–3.7) for A/H3N2, 1.1 (95% CI: .9–1.4) for B/Yamagata, and 1.1 (95% CI: .9–1.3) for B/Victoria. At 6 months, ccIIV4 recipients had similar GMTs to IIV4, whereas RIV4 recipients had higher GMTs against A/H3N2 and B/Yamagata. Conclusions RIV4 resulted in improved antibody responses by HI and MN compared to egg-based vaccines against 3 of 4 cell-grown vaccine strains 1 month postvaccination, suggesting a possible additional benefit from RIV4., In this randomized trial among healthcare personnel comparing antibody responses to cell-culture based and recombinant influenza vaccines (RIV4) versus standard-dose egg-based vaccines, RIV4 recipients had higher antibody responses against 3 cell-grown vaccine strains suggesting a possible additional benefit from RIV4.

Background Seasonal influenza causes substantial morbidity and mortality in older adults. High-dose inactivated influenza vaccine (HD-IIV), with increased antigen content compared to standard-dose influenza vaccines (SD-IIV), is licensed for use in people aged ≥65 years. We sought to evaluate the effectiveness of HD-IIV and SD-IIV for prevention of influenza-associated hospitalizations. Methods Hospitalized patients with acute respiratory illness were enrolled in an observational vaccine effectiveness study at 8 hospitals in the United States Hospitalized Adult Influenza Vaccine Effectiveness Network during the 2015–2016 and 2016–2017 influenza seasons. Enrolled patients were tested for influenza, and receipt of influenza vaccine by type was recorded. Effectiveness of SD-IIV and HD-IIV was estimated using a test-negative design (comparing odds of influenza among vaccinated and unvaccinated patients). Relative effectiveness of SD-IIV and HD-IIV was estimated using logistic regression. Results Among 1487 enrolled patients aged ≥65 years, 1107 (74%) were vaccinated; 622 (56%) received HD-IIV, and 485 (44%) received SD-IIV. Overall, 277 (19%) tested positive for influenza, including 98 (16%) who received HD-IIV, 87 (18%) who received SD-IIV, and 92 (24%) who were unvaccinated. After adjusting for confounding variables, effectiveness of SD-IIV was 6% (95% confidence interval [CI] −42%, 38%) and that of HD-IIV was 32% (95% CI −3%, 54%), for a relative effectiveness of HD-IIV versus SD-IIV of 27% (95% CI −1%, 48%). Conclusions During 2 US influenza seasons, vaccine effectiveness was low to moderate for prevention of influenza hospitalization among adults aged ≥65 years. High-dose vaccine offered greater effectiveness. None of these findings were statistically significant.

Identifying optimal priming strategies for children2 years could substantially improve the public health benefits of influenza vaccines. Adjuvanted seasonal influenza vaccines were designed to promote a better immune response among young vaccine-naïve children.We systematically reviewed randomized trials to assess hemagglutination inhibition (HAI) antibody response to MF59-adjuvanted inactivated influenza vaccine (aIIV) versus nonadjuvanted IIV among children. We estimated pooled ratios of post-vaccination HAI geometric mean titer (GMT) for aIIV versus IIV and confidence intervals (CIs) using the pooled variances derived from reported CIs.Mean age was 28 months (range, 6-72 months). Children received vaccines with either 7.5 μg (6-35 months) or 15 μg (≥36 months) hemagglutinin of each strain depending on age. Seven of eight trials administered trivalent vaccines and one used quadrivalent vaccine. Pooled post-vaccination GMT ratios against the three influenza vaccine strains were 2.5-3.5 fold higher after 2-dose-aIIV versus 2-dose-IIV among children 6-72 months, and point estimates were higher among children 6-35 months compared with older children. When comparing 1-dose-aIIV to 2-dose-IIV doses, pooled GMT ratios were not significantly different against A/H1N1 (1.0; 95% CI: 0.5-1.8; p = 0.90) and A/H3N2 viruses (1.0; 95% CI: 0.7-1.5; p = 0.81) and were significantly lower against B viruses (0.6; 95% CI: 0.4-0.8; p 0.001) for both age groups. Notably, GMT ratios for vaccine-mismatched heterologous viruses after 2-dose-aIIV compared with 2-dose-IIV were higher against A/H1N1 (2.0; 95% CI: 1.1-3.4), A/H3N2 (2.9; 95% CI: 1.9-4.2), and B-lineage viruses (2.1; 95% CI: 1.8-2.6).Two doses of adjuvanted IIV consistently induced better humoral immune responses against Type A and B influenza viruses compared with nonadjuvanted IIVs in young children, particularly among those 6-35 months. One adjuvanted IIV dose had a similar response to two nonadjuvanted IIV doses against Type A influenza viruses. Longer-term benefits from imprinting and cell-mediated immunity, including trials of clinical efficacy, are gaps that warrant investigation.

Background The evolution of influenza A viruses results in birth cohorts that have different initial influenza virus exposures. Historically, A/H3 predominant seasons have been associated with more severe influenza-associated disease; however, since the 2009 pandemic, there are suggestions that some birth cohorts experience more severe illness in A/H1 predominant seasons. Methods United States influenza virologic, hospitalization, and mortality surveillance data during 2000–2017 were analyzed for cohorts born between 1918 and 1989 that likely had different initial influenza virus exposures based on viruses circulating during early childhood. Relative risk/rate during H3 compared with H1 predominant seasons during prepandemic versus pandemic and later periods were calculated for each cohort. Results During the prepandemic period, all cohorts had more influenza-associated disease during H3 predominant seasons than H1 predominant seasons. During the pandemic and later period, 4 cohorts had higher hospitalization and mortality rates during H1 predominant seasons than H3 predominant seasons. Conclusions Birth cohort differences in risk of influenza-associated disease by influenza A virus subtype can be seen in US influenza surveillance data and differ between prepandemic and pandemic and later periods. As the population ages, the amount of influenza-associated disease may be greater in future H1 predominant seasons than H3 predominant seasons.

Background Human immunodeficiency virus (HIV)–infected persons are at a higher risk of severe influenza. Although we have shown that a standard-dose intradermal influenza vaccine versus a standard-dose intramuscular influenza vaccine does not result in differences in hemagglutination-inhibition titers in this population, a comprehensive examination of cell-mediated immune responses remains lacking. Methods Serological, antigen-specific B-cell, and interleukin 2–, interferon γ–, and tumor necrosis factor α–secreting T-cell responses were assessed in 79 HIV-infected men and 79 HIV-uninfected men. Results The route of vaccination did not affect the immunoglobulin A and immunoglobulin G (IgG) plasmablast or memory B-cell response, although these were severely impaired in the group with a CD4+ T-cell count of Conclusions The route of vaccination had no effect on antibody responses, antibody avidity, T-cell responses, or B-cell responses in HIV-infected or HIV-uninfected subjects. With the serological and cellular immune responses to influenza vaccination being impaired in HIV-infected individuals with a CD4+ T-cell count of Clinical trials registration NCT01538940.

Background The ACIP recommends influenza and Tdap vaccination during pregnancy to reduce the risk of influenza and pertussis in the mother and her infant. We assessed influenza and Tdap vaccination coverage and associated factors among pregnant women enrolled in PREVAIL, a prospective birth cohort study in Cincinnati, OH. We assessed sensitivity and specificity of self report for both vaccines against state registry, maternal healthcare provider, and work-place records. Methods We enrolled and interviewed 265 pregnant women regarding self-reported receipt of influenza and Tdap vaccines, and obtained vaccine records from registry, electronic medical record, provider, employer, or pharmacy. We grouped subjects by documented vaccination status and analyzed demographic variables and vaccine attitudes regarding efficacy, safety, and hesitancy using unadjusted Fisher exact tests. We analyzed sensitivity and specificity of maternal recall. Results We identified documentation of influenza and Tdap vaccine receipt during pregnancy in 172/265 (64.9%) and 238/265 (89.8%) of women, respectively (Figure 1); by self report, 177/265 (66.8%) reported receiving influenza and 221/265 (83.4%) Tdap vaccine. The two most common primary reasons cited for receiving influenza vaccine were “to protect my baby” (36.7%) and “to protect myself” (26%; Figure 2). Pregnant women were more likely to get Tdap vaccine if a healthcare worker recommended it (OR 5.4). Subjects were more likely to get influenza vaccine if they believed it was effective in preventing influenza in themselves (OR 9.0) or their babies (OR 8.1). While positive recall had a high concordance (95.2% and 93.4% for influenza and Tdap, respectively), 12.5% and 32.1% of mothers incorrectly recalled not receiving an influenza or Tdap vaccine, respectively, that was documented as received in the records (Figure 3). Conclusion We found high concordance between maternal recall and verification for both influenza and Tdap vaccines. In this single-site cohort of 265 women, self report was a reliable measure of vaccination status among pregnant women. Provider communication to pregnant women regarding effectiveness of influenza and Tdap vaccinations for themselves and their infants may lead to higher maternal vaccination rates. Disclosures All authors: No reported disclosures.

Background Annual national estimates of influenza vaccine effectiveness (VE) typically measure protection against outpatient medically attended influenza illness. We assessed influenza VE in preventing laboratory-confirmed influenza hospitalization in children across two influenza A(H3N2)-predominant seasons. Methods Children < 18 years hospitalized with acute respiratory illness were enrolled at 7 pediatric hospitals in the New Vaccine Surveillance Network. We included subjects ≥6 months with ≤10 days of symptoms enrolled during the 2016–2017 and 2017–2018 seasons (date of first through last influenza-positive case for each site). Combined mid-turbinate and throat swabs were tested using molecular assays. We estimated age-stratified VE from a test-negative design using logistic regression to compare the odds of vaccination among cases positive for influenza with controls testing negative, adjusting for age, enrollment month, site, underlying comorbidities, and race/ethnicity. Full/partial vaccination was defined using ACIP criteria. We verified vaccine receipt from state immunization registries and/or provider records. Results Among 3441 children with complete preliminary data, in 2016–2017, 156/1,710 (9%) tested positive for influenza: 91 (58%) with influenza A(H3N2), 5 (3%) with A(H1N1), and 60 (38%) with B viruses. In 2017–2018, 193/1,731 (11%) tested positive: 87 (45%) with influenza A(H3N2), 47 (24%) with A(H1N1), and 58 (30%) with B. VE for all vaccinated children (full and partial) against any influenza was 48% (95% confidence interval, 26%–63%) in 2016–2017 and 45% (24%–60%) in 2017–2018. Combining seasons, VE for fully and partially vaccinated children against any influenza type was 46% (32%–58%); by virus, VE was 30% (4%–49%) for influenza A(H3N2), 71% (46%–85%) for A(H1N1), and 57% (36%–70%) for B viruses. There was no statistically significant difference in VE by age or full/partial vaccination status for any virus (table). Conclusion Vaccination in the 2016–2017 and 2017–2018 seasons nearly halved the risk of children being hospitalized with influenza. These findings support the use of vaccination to prevent severe illness in children. Our study highlights the need for a better understanding of the lower VE against influenza A(H3N2) viruses. Disclosures All Authors: No reported Disclosures.

Background Influenza vaccination has been shown to reduce influenza risk in pregnant women and their infants who are not yet age-eligible for vaccine. Ascertainment of vaccination history is important for vaccine safety and effectiveness evaluations. Our goals were to (a) determine coverage, location, and timing of maternal influenza vaccination and (b) compare a subset of self-reported influenza vaccinations with documented vaccine records. Methods We enrolled children < 18 years. with acute respiratory illness in 7 pediatric hospitals and emergency departments in the New Vaccine Surveillance Network from December 1, 2016 to October 31, 2018. We interviewed all mothers of enrolled infants < 1 year, and obtained mother’s influenza vaccine information while pregnant. As an option, sites obtained maternal influenza vaccine records from reported sources (e.g., registries, provider records, pharmacies). Results Among 5,458 mothers, 2,944 (54%) self-reported receiving influenza vaccine during pregnancy (57% in 2016–2017; 51% in 2017–2018), varying from 49% to 74% by site. Among self-reported vaccinees, 17%, 36%, and 47% received vaccine during their first, second, and third trimester, respectively. Most women (76%) were vaccinated at their OB/GYN or midwife office, 7% at their primary care provider, 7% at their workplace, and 5% at a retail pharmacy. Among 1,338 infants < 6 months. during early influenza season (i.e., born from June to August) and thus ineligible for vaccination, only 46% of mothers reported receiving vaccine during pregnancy (42% reported not receiving it, 12% were unsure). Of 2,242 women for whom vaccine verification was attempted, 1,491 (67%) self-reported receiving influenza vaccine during pregnancy; of those, documentation of vaccine receipt was found for 901 (60%). Conclusion Influenza vaccination coverage among pregnant women was suboptimal, potentially increasing the risk of influenza in unvaccinated pregnant women. Infants born to unvaccinated women, particularly those born from June to August, may also be at higher risk since they are not age-eligible to receive vaccine before influenza season. The optimal approach to ascertainment of maternal vaccination history with accuracy and completeness merits further investigation. Disclosures All authors: No reported disclosures.

Background Influenza vaccination may reduce illness severity among those with influenza; however, data are limited. We determined whether outcomes were less severe among vaccinated compared with unvaccinated adults hospitalized with influenza over 5 seasons. Methods We included adults (≥18 years) hospitalized with laboratory-confirmed influenza during seasons 2013–2014 through 2017–2018 and identified through the US Influenza Hospitalization Surveillance Network (FluSurv-NET). Vaccination status was obtained through medical records, vaccine registries, and interviews. We excluded patients who were institutionalized, did not receive antivirals, or had unknown vaccine status or vaccine receipt Results Among 67,452 adults hospitalized with influenza, 43,608 were included; 47% were 18–64 years (38% vaccinated) and 53% were ≥65 years (65% vaccinated). Among patients with influenza A(H1N1)pdm09, vaccination was associated with decreased odds of ICU admission (odds ratio (OR) 0.81; OR 0.72) and MV (OR 0.66; OR 0.54) in adults 18–64 and ≥65 years, respectively; decreased odds of pneumonia (OR 0.83), death (OR 0.64) and shortened ICU LOS (relative hazard (RH) 0.82) in adults 18–64 years; and shortened hospital LOS (RH 0.91) in adults ≥65 years (figure). Vaccination was not associated with attenuation of severe outcomes in patients with influenza A(H3N2) and B. Conclusion Vaccination was associated with reduced odds of severe outcomes, including death, by up to 36% in adults hospitalized with influenza A(H1N1)pdm09. All adults without contraindications should receive annual influenza vaccination as there is evidence that it can improve outcomes among those who develop influenza despite vaccination. Disclosures All Authors: No reported Disclosures.

Background Seasonal influenza causes substantial morbidity and mortality, and older adults are disproportionately affected. Newer vaccines have been developed for use in people 65 years and older, including a trivalent inactivated vaccine with a 4-fold higher dose of antigen (IIV-HD). In recent years, the use of IIV-HD has increased sufficiently to evaluate its effectiveness compared with standard-dose inactivated influenza vaccines (IIV-SD). Methods Hospitalized patients with acute respiratory illness were enrolled in an observational vaccine effectiveness study at 8 hospitals in 4 states participating in the United States Hospitalized Adult Influenza Vaccine Effectiveness Network during the 2015–2016 and 2016–2017 influenza seasons. Predominant influenza A virus subtypes were H1N1 and H3N2, respectively, during these seasons. All enrolled patients were tested for influenza virus with polymerase chain reaction. Receipt and type of influenza vaccine was determined from electronic records and chart review. Odds of laboratory-confirmed influenza were compared among vaccinated and unvaccinated patients. Relative odds of laboratory-confirmed influenza were determined for patients who received IIV-HD or IIV-SD, and adjusted for potential confounding variables via logistic regression. Results Among 1,744 enrolled patients aged ≥ 65 years, 1,105 (63%) were vaccinated; among those vaccinated, 621 (56%) received IIV-HD and 484 (44%) received IIV-SD. Overall, 315 (18%) tested positive for influenza, including 97 (6%) who received IIV-HD, 86 (5%) who received IIV-SD, and 132 (8%) who were unvaccinated. Controlling for age, race, sex, enrollment site, date of illness, index of comorbidity, and influenza season, the adjusted odds of influenza among patients vaccinated with IIV-HD vs. IIV-SD were 0.72 (P = 0.06, 95% CI: 0.52 to 1.01). Conclusion Comparison of high-dose vs. standard-dose vaccine effectiveness during 2 recent influenza seasons (1 H1N1 and 1 H3N2-predominant) suggested relative benefit (nonsignificant) of high-dose influenza vaccine in protecting against influenza-associated hospitalization among persons aged 65 years and older; additional years of data are needed to confirm this finding. Disclosures H. K. Talbot, sanofi pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none.