Providing Additional “Muscle” for Older Adults Through Optimal Influenza Vaccine Selection

2018 ◽  
Vol 52 (9) ◽  
pp. 936-941 ◽  
Author(s):  
John A. Dougherty ◽  
Elias B. Chahine
Keyword(s):  
Older Adults ◽  
Influenza Vaccine ◽  
Disease Control ◽  
Older Patients ◽  
Standard Dose ◽  
Influenza Vaccines ◽  
High Dose ◽  
Control And Prevention ◽  
Reasonable Evidence ◽  
Age Appropriate

Immunization is the best strategy to protect individuals from influenza; however, older adults tend to respond less favorably to vaccines because of immunosenescence. The Centers for Disease Control and Prevention states that any licensed, recommended, and age-appropriate influenza vaccine may be used in older adults despite reasonable evidence suggesting that the high-dose and, to a lesser extent, the adjuvanted and recombinant influenza vaccines provide better protection than the standard-dose vaccines in this vulnerable population. In this era of precision medicine, clinicians can preferentially recommend these contemporary vaccines to equip their older patients with the best possible protection against influenza.

High-Dose Inactivated Influenza Vaccine Quadrivalent for Older Adults

2020 ◽  
Vol 55 (1) ◽  
pp. 89-97
Author(s):  
Elias B. Chahine
Keyword(s):  
Older Adults ◽  
Influenza Vaccine ◽  
English Language ◽  
Standard Dose ◽  
Data Extraction ◽  
High Dose ◽  
Efficacy And Safety ◽  
Study Selection ◽  
Control And Prevention ◽  
Age Appropriate

Objective: To review the efficacy and safety of the high-dose inactivated influenza vaccine quadrivalent (HD-IIV4) in the prevention of influenza in older adults. Data Sources: A literature search was performed using PubMed and Google Scholar with the search terms high-dose, influenza vaccine, and quadrivalent. Other resources included the Centers for Disease Control and Prevention (CDC), the prescribing information, and the manufacturer’s website. Study Selection and Data Extraction: All relevant English-language articles of studies assessing the efficacy and safety of HD-IIV4 were included. Data Synthesis: HD-IIV4 is licensed by the Food and Drug Administration for the prevention of influenza in adults aged 65 years and older. The safety and immunogenicity of HD-IIV4 was demonstrated in a phase 3 trial, and the efficacy of the trivalent formulation (HD-IIV3) was demonstrated in a phase 3b-4 trial. HD-IIV4 carries a warning regarding the occurrence of Guillain-Barré syndrome. Adverse reactions, including injection-site pain and myalgia, were reported more frequently with HD-IIV4 than with HD-IIV3. Relevance to Patient Care and Clinical Practice: Although the CDC recommends any age-appropriate influenza vaccine for adults aged 65 years and older, HD-IIV4 was associated with improved immunogenicity against the added B strain and HD-IIV3 provided better protection against influenza than the standard-dose vaccine. Other influenza vaccines have weaker evidence of efficacy in older adults. Therefore, HDIIV4 should be recommended as the vaccine of choice in adults aged 65 years and older. Conclusion: HD-IIV4 has proven immunogenic, safe, and effective in preventing influenza in older adults and should be recommended as the vaccine of choice in this patient population.

Comparative Reactogenicity of Enhanced Influenza Vaccines in Older Adults

2020 ◽  
Vol 222 (8) ◽  
pp. 1383-1391
Author(s):  
Benjamin J Cowling ◽  
Mark G Thompson ◽  
Tiffany W Y Ng ◽  
Vicky J Fang ◽  
Ranawaka A P M Perera ◽  
...  
Keyword(s):  
Older Adults ◽  
Influenza Vaccine ◽  
Standard Dose ◽  
Controlled Trial ◽  
Community Dwelling ◽  
Influenza Vaccines ◽  
High Dose ◽  
Systemic Reactions ◽  
Local Reactions ◽  
Systemic Symptoms

Abstract Background We analyzed data from a randomized controlled trial on the reactogenicity of 3 enhanced influenza vaccines compared with standard-dose (SD) inactivated influenza vaccine. Methods We enrolled community-dwelling older adults in Hong Kong, and we randomly allocated them to receive 2017–2018 northern hemisphere formulations of SD vaccine (FluQuadri; Sanofi Pasteur), MF59-adjuvanted vaccine (FLUAD; Seqirus), high-dose (HD) vaccine (Fluzone High-Dose; Sanofi Pasteur), or recombinant hemagglutinin vaccine (Flublok; Sanofi Pasteur). Local and systemic reactions were evaluated at days 1, 3, 7, and 14 after vaccination. Results Reported reactions were generally mild and short-lived. Systemic reactions occurred in similar proportions of participants by vaccine. Some local reactions were slightly more frequently reported among recipients of the MF59-adjuvanted and HD vaccines than among SD vaccine recipients. Participants reporting feverishness 1 day after vaccination had mean fold rises in postvaccination hemagglutination inhibition titers that were 1.85-fold higher (95% confidence interval, 1.01–3.38) for A(H1N1) than in those who did not report feverishness. Conclusions Some acute local reactions were more frequent after vaccination with MF59-adjuvanted and HD influenza vaccines, compared with SD inactivated influenza vaccine, whereas systemic symptoms occurred at similar frequencies in all groups. The association between feverishness and immunogenicity should be further investigated in a larger population. Clinical Trials Registration NCT03330132.

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

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S764-S764 ◽  
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.

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

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.

scholarly journals Choice of influenza vaccine in people over 65 years old. Analysis of reports from international vaccination advisory committees

2021 ◽  
Author(s):  
Alberto Pérez-Rubio ◽  
◽  
José Javier Castrodeza ◽  
José María Eiros
Keyword(s):  
Influenza Vaccine ◽  
Influenza Vaccines ◽  
High Dose ◽  
Advisory Committees ◽  
Individual Level ◽  
Age Appropriate ◽  
Working Groups ◽  
Flu Vaccine ◽  
The Individual ◽  
The Uk

Introduction. Annual recommendations on influenza vaccine use in different countries are developed by influenza-specific working groups within their Immunization Advisory Committees. Adults aged 65 years and over are included in the groups for which vaccination against influenza is particularly recommended due to the morbidity associated. A variety of influenza vaccines are available, some of which boosted immunity, are licensed for use only in this specific age group, where the immune response to traditional influenza vaccines may be suboptimal. We analyze the main annual recommendations on the use of the influenza vaccine issued by advisory committees on immunization for the population over 65 years of age. Material and methods. The latest influenza vaccination guidelines have been selected and the recommendations for people over 65 years of age published by the main vaccination advisory committees have been reviewed. Results. The UK Advisory Committee (JCVI) recommends the use of Quadruvalent Inactivated Influenza Vaccine with Adjuvant (aQIV) or High Dose Quadrivalent Inactivated Influenza Vaccine (QIV-HD). The US committee (ACIP) does not express a preference for any type of vaccine. The Australian committee (ATAGI) preferably recommends adjuvanted influenza vaccine. The advisory committees of Canada and Germany (NACI, STIKO) and the European Center for Disease Control (Ecdc) recommend using any of the age-appropriate flu vaccines available, although they bet on the use of inactivated quadrivalent flu vaccine high dose at the individual level for those over 65 years. Conclusion. It is necessary further studies and improvement in their quality that analyze the different vaccines available and their comparability, although the use of reinforced immunity vaccines is generally recommended in the population over 65 years of age.

scholarly journals Key Determinants of Cell-Mediated Immune Responses: A Randomized Trial of High Dose Vs. Standard Dose Split-Virus Influenza Vaccine in Older Adults

2021 ◽  
Vol 2 ◽  
Author(s):  
Chris P. Verschoor ◽  
Laura Haynes ◽  
Graham Pawelec ◽  
Mark Loeb ◽  
Melissa K. Andrew ◽  
...  
Keyword(s):  
Older Adults ◽  
Immune Responses ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Standard Dose ◽  
Serum Antibody ◽  
High Dose ◽  
Post Vaccination ◽  
Antibody Titers ◽  
Virus Influenza

Background: Efforts to improve influenza vaccine effectiveness in older adults have resulted in some successes, such as the introduction of high-dose split-virus influenza vaccine (HD-SVV), yet studies of cell-mediated immune responses to these vaccines remain limited. We have shown that granzyme B (GrB) activity in influenza A/H3N2 challenged peripheral blood mononuclear cells (PBMC) correlates with protection against influenza following standard dose vaccination (SD-SVV) in older adults. Further, the interferon-γ (IFNγ) to interleukin-10 (IL-10) ratio can be a correlate of protection.Methods: In a double-blind trial (ClinicalTrials.gov NCT02297542) older adults (≥65 years, n = 582) were randomized to receive SD-SVV or HD-SVV (Fluzone®) from 2014/15 to 2017/18. Young adults (20–40 years, n = 79) received SD-SVV. At 0, 4, 10, and 20 weeks post-vaccination, serum antibody titers, IFNγ, IL-10, and inducible GrB (iGrB) were measured in ex vivo influenza-challenged PBMC. iGrB is defined as the fold change in GrB activity from baseline levels (bGrB) in circulating T cells. Responses of older adults were compared to younger controls, and in older adults, we analyzed effects of age, sex, cytomegalovirus (CMV) serostatus, frailty, and vaccine dose.Results: Prior to vaccination, younger compared to older adults produced significantly higher IFNγ, IL-10, and iGrB levels. Relative to SD-SVV recipients, older HD-SVV recipients exhibited significantly lower IFNγ:IL-10 ratios at 4 weeks post-vaccination. In contrast, IFNγ and iGrB levels were higher in younger SD vs. older SD or HD recipients; only the HD group showed a significant IFNγ response to vaccination compared to the SD groups; all three groups showed a significant iGrB response to vaccination. In a regression analysis, frailty was associated with lower IFNγ levels, whereas female sex and HD-SVV with higher IL-10 levels. Age and SD-SVV were associated with lower iGrB levels. The effect of prior season influenza vaccination was decreased iGrB levels, and increased IFNγ and IL-10 levels, which correlated with influenza A/H3N2 hemagglutination inhibition antibody titers.Conclusion: Overall, HD-SVV amplified the IL-10 response consistent with enhanced antibody responses, with little effect on the iGrB response relative to SD-SVV in either younger or older adults. These results suggest that enhanced protection with HD-SVV is largely antibody-mediated.Clinical Trial Registration: ClinicalTrials.gov (NCT02297542).

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

2020 ◽  
Author(s):  
Joshua D Doyle ◽  
Lauren Beacham ◽  
Emily T Martin ◽  
H Keipp Talbot ◽  
Arnold Monto ◽  
...  
Keyword(s):  
United States ◽  
Older Adults ◽  
Influenza Vaccine ◽  
Standard Dose ◽  
Relative Effectiveness ◽  
Respiratory Illness ◽  
The United States ◽  
Vaccine Effectiveness ◽  
High Dose ◽  
Confounding Variables

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.

scholarly journals Effectiveness of the MF59-adjuvanted trivalent or quadrivalent seasonal influenza vaccine among adults 65 years of age or older, a systematic review and meta-analysis

2021 ◽  
Author(s):  
Brenda Coleman ◽  
Ruth Sanderson ◽  
Mendel Haag ◽  
Ian McGovern
Keyword(s):  
Influenza Vaccine ◽  
Seasonal Influenza ◽  
Standard Dose ◽  
Meta Analysis ◽  
Grey Literature ◽  
Influenza Vaccines ◽  
High Dose ◽  
Case Control Studies ◽  
Cluster Randomized ◽  
Meta Analyses

Background: Standard dose seasonal influenza vaccines often produce modest immunogenic responses in adults ≥65 years old. MF59 is intended to elicit a greater magnitude and increased breadth of immune response. Objective: To determine the effectiveness of seasonal MF59-adjuvanted trivalent/quadrivalent influenza vaccine (aTIV/aQIV) relative to no vaccination or vaccination with standard or high dose egg-based influenza vaccines among people ≥65 years old. Methods: Cochrane methodological standards and PRISMA-P guidelines were followed. Real-world evidence from non-interventional studies published in peer reviewed journals and grey literature from 1997 through to July 15, 2020, including cluster-randomized trials, were eligible. Two reviewers independently extracted data and risk of bias was assessed using the ROBINS-I tool. Results: Twenty-one studies conducted during the 2006/07-2019/20 influenza seasons were included in the qualitative review; 16 in the meta-analyses. Meta-analysis of test-negative studies found that aTIV reduced medical encounters due to lab-confirmed influenza with pooled estimates of 40.7% (95% CI: 21.9, 54.9; I2=0%) for general practitioner visits and 58.5% (40.7, 70.9; I2=52.9%) for hospitalized patients. The pooled estimate of VE from case-control studies was 51.3% (39.1, 61.1; I2=0%) against influenza- or pneumonia-related hospitalization. The pooled estimates for the relative VE of aTIV for the prevention of influenza related medical encounters were 13.9% (4.2, 23.5; I2=95.9%) compared with TIV, 13.7% (3.1, 24.2; I2=98.8%) compared with QIV, and 2.8% (-2.9, 8.5; I2=94.5%) compared with HD TIV. Conclusions: Among adults ≥65 years aTIV demonstrated significant absolute VE, improved relative VE compared to non-adjuvanted standard-dose TIV/QIV, and comparable relative VE to high-dose TIV.

Efficacy of High-Dose versus Standard-Dose Influenza Vaccine in Older Adults

2014 ◽  
Vol 371 (7) ◽  
pp. 635-645 ◽  
Author(s):  
Carlos A. DiazGranados ◽  
Andrew J. Dunning ◽  
Murray Kimmel ◽  
Daniel Kirby ◽  
John Treanor ◽  
...  
Keyword(s):  
Older Adults ◽  
Influenza Vaccine ◽  
Standard Dose ◽  
High Dose
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