Relative and Absolute Effectiveness of High-Dose and Standard-Dose Influenza Vaccine Against Influenza-Related Hospitalization Among Older Adults—United States, 2015–2017

Abstract 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.

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150. Relative Effectiveness of High-Dose and Standard-Dose Influenza Vaccine Against Influenza-Related Hospitalization Among Older Adults—United States, 2015–2017

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy209.020 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S10-S10

Author(s):

Joshua Doyle ◽

Lauren Beacham ◽

Elif Alyanak ◽

Manjusha Gaglani ◽

Emily T Martin ◽

...

Keyword(s):

United States ◽

Older Adults ◽

Influenza Vaccine ◽

Influenza A ◽

Standard Dose ◽

Relative Effectiveness ◽

The United States ◽

Vaccine Effectiveness ◽

High Dose ◽

Research Grant

Abstract 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.

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Influenza vaccine effectiveness against hospitalization in the United States, 2019-2020

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa800 ◽

2020 ◽

Author(s):

Mark W Tenforde ◽

H Keipp Talbot ◽

Christopher H Trabue ◽

Manjusha Gaglani ◽

Tresa M McNeal ◽

...

Keyword(s):

United States ◽

Influenza Vaccine ◽

Influenza Vaccination ◽

Respiratory Illness ◽

The United States ◽

Vaccine Effectiveness ◽

Influenza Viruses ◽

Current Season ◽

Hospital Resources ◽

Negative Controls

Abstract Background Influenza causes significant morbidity and mortality and stresses hospital resources during periods of increased circulation. We evaluated the effectiveness of the 2019-2020 influenza vaccine against influenza-associated hospitalizations in the United States. Methods We included adults hospitalized with acute respiratory illness at 14 hospitals and tested for influenza viruses by reserve transcription polymerase chain reaction. Vaccine effectiveness (VE) was estimated by comparing the odds of current-season influenza vaccination in test-positive influenza cases versus test-negative controls, adjusting for confounders. VE was stratified by age and major circulating influenza types along with A(H1N1)pdm09 genetic subgroups. Results 3116 participants were included, including 18% (553) influenza-positive cases. Median age was 63 years. Sixty-seven percent (2079) received vaccination. Overall adjusted VE against influenza viruses was 41% (95% confidence interval [CI]: 27-52). VE against A(H1N1)pdm09 viruses was 40% (95% CI: 24-53) and 33% against B viruses (95% CI: 0-56). Of the two major A(H1N1)pdm09 subgroups (representing 90% of sequenced H1N1 viruses), VE against one group (5A+187A,189E) was 59% (95% CI: 34-75) whereas no significant VE was observed against the other group (5A+156K) [-1%, 95% CI: -61-37]. Conclusions In a primarily older population, influenza vaccination was associated with a 41% reduction in risk of hospitalized influenza illness.

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A retrospective cohort study assessing relative effectiveness of adjuvanted versus high-dose trivalent influenza vaccines among older adults in the United States during the 2018–19 influenza season

Vaccine ◽

10.1016/j.vaccine.2021.03.054 ◽

2021 ◽

Author(s):

Stephen I. Pelton ◽

Victoria Divino ◽

Maarten J. Postma ◽

Drishti Shah ◽

Joaquin Mould-Quevedo ◽

...

Keyword(s):

United States ◽

Older Adults ◽

Cohort Study ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Influenza Season ◽

Relative Effectiveness ◽

The United States ◽

Influenza Vaccines ◽

High Dose

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LB14. Safety and Immunogenicity of High-Dose Quadrivalent Influenza Vaccine Administered by Intramuscular Route in Subjects Aged 65 Years and Older

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy229.2188 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S764-S764 ◽

Cited By ~ 1

Author(s):

Lee-Jah Chang ◽

Ya Meng ◽

Helene Janosczyk ◽

Victoria Landolfi ◽

H Keipp Talbot ◽

...

Keyword(s):

United States ◽

Immune Response ◽

Influenza Vaccine ◽

Standard Dose ◽

The United States ◽

Influenza Vaccines ◽

High Dose ◽

Post Vaccination ◽

B Lineage ◽

Research Grant

Abstract Background Older adults (≥65 years of age) remain at increased risk of influenza because they do not respond to standard dose influenza vaccines as well as younger adults. A high dose, inactivated trivalent influenza vaccine, IIV3-HD, containing four times the antigen content (60 µg hemagglutinin per influenza strain) of standard-dose influenza vaccines has been available in the United States since 2010. Two distinct B influenza lineages (Victoria and Yamagata) have co-circulated for over a decade, making it difficult to predict which will predominate the next season. IIV4-HD has been developed to address the frequent influenza B strain mismatches by incorporating a strain from each B lineage. This pivotal Phase III study evaluated the safety and immunogenicity of IIV4-HD as compared with two IIV3-HD vaccines. Method A randomized, modified double-blind, multicenter study (NCT03282240) was conducted in 2670 healthy subjects in the United States, who were randomly assigned to receive IIV4-HD, a licensed IIV3-HD, or an IIV3-HD with the alternate B influenza strain. Using the hemagglutinin inhibition (HAI) assay at baseline and 28 days after vaccination, post-vaccination geometric mean titers and seroconversion rates were measured. Safety data were collected through 6 months post-vaccination. Result IIV4-HD was noninferior to the licensed IIV3-HD and the investigational IIV3-HD (containing the alternate B strain) for all four influenza strains as assessed by HAI GMTs and seroconversion rates. Moreover, IIV4-HD induced a superior immune response (HAI GMTs and seroconversion rates) compared with the immune response induced by the IIV3-HD that does not contain the corresponding B strain. Reactogenicity profiles were comparable across all study groups. Most unsolicited adverse events were of Grade 1 or Grade 2 intensity. One serious adverse event considered related by the Investigator was reported in the IIV4-HD group. Conclusion Vaccination of adults 65 years of age and older with IIV4-HD was found to be noninferior to two IIV3-HD vaccines with a similar safety profile. The addition of a second B lineage strain does not adversely affect the safety or immunogenicity profile of IIV4-HD compared with IIV3-HD. Disclosures L. J. Chang, Sanofi Pasteur: Employee, Salary. Y. Meng, Sanofi Pasteur: Employee, Salary. H. Janosczyk, Sanofi Pasteur: Employee, Salary. V. Landolfi, Sanofi Pasteur: Employee, Salary. H. K. Talbot, Sanofi Pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none.

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2737. Comparison of Antibody Responses to Vaccination with a Pure Hemagglutinin Influenza Vaccine (rHA) and Licensed Subvirion Influenza Vaccine Made in Eggs or Cell Culture in Adults 60 Years and Older

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2415 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S963-S963

Author(s):

Moumita Sarker ◽

Angela Branche ◽

Michael Peasley ◽

David Topham

Keyword(s):

Older Adults ◽

Influenza Vaccine ◽

Vaccine Development ◽

Standard Dose ◽

Geometric Mean ◽

The United States ◽

Antibody Responses ◽

Influenza B Virus ◽

Influenza B ◽

High Dose

Abstract Background Influenza is associated with increased mortality and morbidity for older adults. High-dose egg grown trivalent inactivated influenza vaccine (Fluzone HD) is safe and provides superior immune responses in older adults compared with standard dose (SD). Recently, two new vaccines have been licensed in the United States: cell cultured inactivated vaccine FluCelVax and baculovirus-expressed pure hemagglutinin (HA) vaccine FluBlok. Data from one study demonstrated higher efficacy with FluBlok than SD Fluzone in older adults. There is no data however comparing HD Fluzone to FluBlok and FluCelVax has not been studied at all. The purpose of this study was to assess hemagglutinin inhibition (HAI) antibody responses to vaccination with three vaccines in adults ≥ 60 years. Methods Adults ≥ 60 years were randomly assigned to receive one of the three vaccines: Fluzone HD, FluBlok and FluCelVax (Figure 1). Active influenza-like illness (ILI) surveillance was conducted with bi-weekly telephone calls. Serum samples were collected prior to vaccination and at day 7, 14, 28 and 180 and antibody responses assessed by HAI titer to A/Singapore/INFIMH-16–0019(H3N2), A/Michigan/45/2015(H1N1) and B/Colorado/6/2017 (Victoria) viruses as well as a circulating H3N2 strain. The primary endpoint was a 4-fold rise in antibody titer at day 28. Results 48 subjects were vaccinated in October 2018. Mean age was 69 and 65% were female. Two subjects reported ILI symptoms and one was positive for infection (H1N1). A majority of subjects demonstrated pre-existing antibody to all three viruses (Figure 2, Blue). Geometric mean titers (GMT) for antibody responses to the influenza A viruses were similar for FluBlok (FB) and HD Fluzone (FZ) but lower for FluCelVax(FCB) subjects (Figure 2, Orange). A higher percent of FlubBlok subjects demonstrated 4-fold rise in antibody responses to the Victoria influenza B virus (FB GMT 140 vs. FZ GMT 116, P = 0.26). Conclusion In this small study, antibody responses were similar or higher in older adults after vaccination with FluBlok compared with Fluzone HD with lower responses demonstrated with FluCelvax. Emerging concerns about HA egg adaptation during vaccine development compels further study to determine the appropriate vaccination strategy for this vulnerable population. Disclosures All authors: No reported disclosures.

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Relative Effectiveness of Cell-Cultured and Egg-Based Influenza Vaccines Among Elderly Persons in the United States, 2017–2018

The Journal of Infectious Diseases ◽

10.1093/infdis/jiy716 ◽

2018 ◽

Vol 220 (8) ◽

pp. 1255-1264 ◽

Cited By ~ 35

Author(s):

Hector S Izurieta ◽

Yoganand Chillarige ◽

Jeffrey Kelman ◽

Yuqin Wei ◽

Yun Lu ◽

...

Keyword(s):

Influenza Vaccine ◽

Interim Analysis ◽

Standard Dose ◽

Relative Effectiveness ◽

The United States ◽

Vaccine Virus ◽

High Dose ◽

Elderly Persons ◽

Medicare Beneficiaries ◽

Quadrivalent Vaccines

Abstract Background The low influenza vaccine effectiveness (VE) observed during the A(H3N2)-dominated 2017–2018 season may be due to vaccine virus adaptation to growth in eggs. We compared the effectiveness of cell-cultured and egg-based vaccines among Medicare beneficiaries. Methods Retrospective cohort study on Medicare beneficiaries aged ≥65 years who received an influenza vaccine (cell-cultured, egg-based quadrivalent; egg-based high-dose, adjuvanted, or standard-dose trivalent) during the 2017–2018 season. We used Poisson regression to evaluate relative VE (RVE) in preventing influenza-related hospital encounters. Results Of >13 million beneficiaries, RVE for cell-cultured vaccines relative to egg-based quadrivalent vaccines was 10% (95% confidence interval [CI], 7%–13%). In a midseason interim analysis, this estimate was 16.5% (95% CI, 10.3%–22.2%). In a 5-way comparison, cell-cultured (RVE, 11%; 95% CI, 8%–14%) and egg-based high-dose (RVE, 9%; 95% CI, 7%–11%) vaccines were more effective than egg-based quadrivalent vaccines. Conclusions The modest VE difference between cell-cultured and egg-based vaccines only partially explains the low overall VE reported by the Centers for Disease Control and Prevention, suggesting that egg adaptation was not the main contributor to the low VE found among individuals aged ≥65 years. The midseason interim analysis we performed demonstrates that our methods can be used to evaluate VE actively during the influenza season.

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Influenza Vaccine Effectiveness in Inpatient and Outpatient Settings in the United States, 2015–2018

Clinical Infectious Diseases ◽

10.1093/cid/ciaa407 ◽

2020 ◽

Author(s):

Mark W Tenforde ◽

Jessie Chung ◽

Emily R Smith ◽

H Keipp Talbot ◽

Christopher H Trabue ◽

...

Keyword(s):

United States ◽

High Risk ◽

Influenza Vaccine ◽

Patient Characteristics ◽

Respiratory Illness ◽

The United States ◽

Vaccine Effectiveness ◽

Influenza Activity ◽

Outpatient Settings ◽

Negative Controls

Abstract Background Demonstration of influenza vaccine effectiveness (VE) against hospitalized illness in addition to milder outpatient illness may strengthen vaccination messaging. Our objective was to compare patient characteristics and VE between United States (US) inpatient and outpatient VE networks. Methods We tested adults with acute respiratory illness (ARI) for influenza within 1 outpatient-based and 1 hospital-based VE network from 2015 through 2018. We compared age, sex, and high-risk conditions. The test-negative design was used to compare vaccination odds in influenza-positive cases vs influenza-negative controls. We estimated VE using logistic regression adjusting for site, age, sex, race/ethnicity, peak influenza activity, time to testing from, season (overall VE), and underlying conditions. VE differences (ΔVE) were assessed with 95% confidence intervals (CIs) determined through bootstrapping with significance defined as excluding the null. Results The networks enrolled 14 573 (4144 influenza-positive) outpatients and 6769 (1452 influenza-positive) inpatients. Inpatients were older (median, 62 years vs 49 years) and had more high-risk conditions (median, 4 vs 1). Overall VE across seasons was 31% (95% CI, 26%–37%) among outpatients and 36% (95% CI, 27%–44%) among inpatients. Strain-specific VE (95% CI) among outpatients vs inpatients was 37% (25%–47%) vs 53% (37%–64%) against H1N1pdm09; 19% (9%–27%) vs 23% (8%–35%) against H3N2; and 46% (38%–53%) vs 46% (31%–58%) against B viruses. ΔVE was not significant for any comparison across all sites. Conclusions Inpatients and outpatients with ARI represent distinct populations. Despite comparatively poor health among inpatients, influenza vaccination was effective in preventing influenza-associated hospitalizations.

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