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.

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.

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.

scholarly journals 2753. Induction of Broadly Cross-Reactive Immune Responses Against A(H3N2) Airuses: Results of a Phase 2 Trial of a Novel Recombinant Hemagglutinin Saponin-Adjuvanted Nanoparticle Seasonal Influenza Vaccine

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S970-S970
Author(s):  
Vivek Shinde ◽  
Rongman Cai ◽  
Joyce S Plested ◽  
Bin Zhou ◽  
Haixia Zhou ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza Vaccine ◽  
Seasonal Influenza ◽  
Antibody Responses ◽  
Antigenic Drift ◽  
Influenza Vaccines ◽  
High Dose ◽  
Phase 2 ◽  
Adaptive Mutations ◽  
Phase 2 Trial

Abstract Background We developed a recombinant saponin-adjuvanted (Matrix-M1) quadrivalent hemagglutinin nanoparticle influenza vaccine (qNIV; NanoFlu) for older adults to address two impediments to efficacy of current, predominantly egg-derived, seasonal influenza vaccines: (1) limited protection against antigenic drift variants, particularly H3N2 viruses; and (2) antigenic mismatch between vaccine and circulating strains due to egg-adaptive mutations arising during manufacturing. In a prior Phase 1 trial, we showed that qNIV induced robust, broadly cross-reactive antibody responses against multiple antigenically drifted H3N2 viruses, which were 47–64% better than the egg-derived comparator trivalent high-dose inactivated influenza vaccine (IIV3-HD; Fluzone-High Dose). We undertook a Phase 2 trial to optimize the formulation of qNIV, and to compare qNIV immune responses to those of IIV3-HD and quadrivalent recombinant influenza vaccine (RIV4; FluBlok). Methods In this phase 2 dose and formulation finding RCT, we randomized 1,375 subjects aged ≥65 years to be immunized with 1 of 7 test vaccines: 5 different formulations of qNIV, IIV3-HD, or RIV4; and assessed wild-type hemagglutinin-inhibition (wt-HAI) and microneutralization (wt-MN) antibody responses (Day 0/28/56). Results Matrix-M1-adjuvanted qNIV induced 15–29% higher wt-HAI titers across 5 vaccine homologous or drifted H3N2 strains at Day 28 relative to unadjuvanted qNIV (statistically significantly superior for 5 of 6 strains tested). At Day 28, several qNIV formulations induced significantly superior wt-HAI titers vs. IIV3-HD (39–45%, 17–22%, and 44–48% greater titers for homologous A/Singapore/INFIMH-16–0019/2016—H3N2, historic-drifted A/Switzerland/9715293/2013—H3N2, and forward-drifted A/Wisconsin/19/2017—H3N2, respectively); and comparable HAI titers vs. RIV4. Wt-MN and wt-HAI data showed concordant patterns across treatment groups. Conclusion qNIV induced superior wt-HAI antibody responses vs. IIV3-HD against homologous or drifted H3N2 viruses and similar responses to RIV4. qNIV may address several critical challenges confronting current egg-derived influenza vaccines, especially in the older adult population. Disclosures All authors: No reported disclosures.

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 Alternative-Dose versus Standard-Dose Trivalent Influenza Vaccines for Immunocompromised Patients: A Meta-Analysis of Randomised Control Trials

2019 ◽  
Vol 8 (5) ◽  
pp. 590
Author(s):  
Lai ◽  
Lin ◽  
Ho ◽  
Chen ◽  
Lee
Keyword(s):  
Systematic Review ◽  
Standard Dose ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Influenza Vaccines ◽  
Optimal Timing ◽  
High Dose ◽  
Vaccination Strategies ◽  
The Individual

The study compared immunogenicity and safety between alternative higher-dose and standard-dose trivalent vaccines in immunocompromised individuals. A literature search was performed using the PubMed, Embase, and Cochrane databases from inception until March 2019 to identify studies comparing the immunogenicity of alternative higher-dose (including high-dose, double-dose, and booster-dose vaccines) and standard-dose trivalent influenza vaccines in patients who underwent transplantation or chemotherapy. Effect estimates from the individual studies were derived and calculated using the DerSimonian and Laird random-effect model. The protocol for this systematic review is registered with PROSPERO (number CRD42019129220). Eight relevant studies involving 1020 patients were included in the systematic review and meta-analysis. The meta-analysis demonstrated that the higher-dose strategy provided had significantly superior seroconversion and seroprotection for A/H1N1 strains than the standard dose. Regarding H3N2 and B strains, no differences in immunogenicity responses were noted. No differences in safety were observed between the vaccination strategies. Alternative higher-dose vaccination strategies appear to associate with superior immunogenicity responses for A/H1N1 strains, and the strategies were generally well tolerated in immunocompromised populations. Future studies should clarify the optimal timing, frequency and dose of vaccination and assess whether these strategies improve vaccine immunogenicity and clinical outcomes.

scholarly journals 2745. Efficacy and Effectiveness of High-Dose Influenza Vaccine for Older Adults by Circulating Strain and Antigenic Match: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S966-S967
Author(s):  
Jason K H Lee ◽  
Gary K L Lam ◽  
Thomas Shin ◽  
Sandrine I Samson ◽  
David P Greenberg ◽  
...  
Keyword(s):  
Systematic Review ◽  
Influenza Vaccine ◽  
Clinical Outcomes ◽  
Vaccine Efficacy ◽  
Hospital Admissions ◽  
Standard Dose ◽  
Influenza Infection ◽  
Meta Analysis ◽  
High Dose ◽  
Seasonal Characteristics

Abstract Background Influenza vaccine efficacy/effectiveness can vary from season to season due in part to the dominant circulating strains and antigenic matching. This study reviews the relative vaccine efficacy/effectiveness (rVE) of high-dose inactivated trivalent influenza vaccine (HD-IIV3) compared with standard-dose influenza vaccines (SD-IIV3) in adults ≥65 years against influenza-associated outcomes across all influenza seasons, during seasons where A/H3N2 or A/H1N1 strains predominantly circulated, and where there was an antigenic match or mismatch of the vaccine and circulating strains. Methods A systematic review was conducted for studies assessing the rVE of HD-IIV3 against probable/laboratory-confirmed influenza-like illness (ILI), hospital admissions, and death in adults ≥65 years. Results from individual seasons were extracted from the identified studies, and surveillance data from each season were used to determine the dominant circulating strains and antigenic match. Results were then stratified based on clinical outcomes and seasonal characteristics and meta-analyzed to estimate pooled rVEs of HD-IIV3. Results 11 studies were meta-analyzed after screening 1,018 studies, providing data on 9 consecutive influenza seasons and over 12 million individuals receiving HD-IIV3. Across all influenza seasons, HD-IIV3 demonstrated improved protection against ILI compared with SD-IIV3 (rVE = 15.9%, 95% CI: 4.1–26.3%). HD-IIV3 was also more effective at preventing hospital admissions from all-causes (rVE = 8.4%, 95% CI: 5.7–11.0%), as well as influenza (rVE = 16.1%, 95% CI: 7.4–24.1%), pneumonia (rVE = 27.3%, 95% CI: 15.3–37.6%), pneumonia/influenza (rVE = 13.4%, 95% CI: 7.3–19.2%) and cardiorespiratory events (rVE = 17.9%, 95% CI: 15.0–20.8%). Some numerical differences were observed in the pooled rVE of outcomes in matched and mismatched seasons and in seasons where A/H3N2 or A/H1N1 strains were predominantly circulating (Table 1). Conclusion Evidence over 9 influenza seasons suggest that HD-IIV3 is consistently more effective than SD-IIV3 at reducing the clinical outcomes associated with influenza infection irrespective of circulating strain and antigenic match. This study was funded by sanofi pasteur. Disclosures All authors: No reported disclosures.

scholarly journals Summary of the National Advisory Committee on Immunization (NACI) Seasonal Influenza Vaccine Statement for 2021–2022

2021 ◽  
Vol 47 (09) ◽  
pp. 372-380
Author(s):  
Angela Sinilaite ◽  
◽  
Kelsey Young ◽  
Robyn Harrison
Keyword(s):  
High Risk ◽  
Influenza Vaccine ◽  
Advisory Committee ◽  
Seasonal Influenza ◽  
Health Agency ◽  
Influenza Vaccines ◽  
High Dose ◽  
Influenza Immunization ◽  
Vaccine Recommendations ◽  
Adults And Children

Background: Several influenza vaccines are authorized in Canada and the evidence on influenza immunization is continually evolving. The National Advisory Committee on Immunization (NACI) provides recommendations regarding the use of seasonal influenza vaccines annually to the Public Health Agency of Canada (PHAC). Objective: To summarize NACI recommendations regarding the use of seasonal influenza vaccines for 2021–2022 and to highlight new recommendations. Methods: Annual influenza vaccine recommendations are developed by NACI's Influenza Working Group for consideration and approval by NACI. The development of the recommendations is based on the NACI evidence-based process. Results: The following new recommendations were made: 1) Influvac® Tetra may be considered as an option among the standard dose quadrivalent inactivated influenza vaccines (IIV4-SD) offered to adults and children three years of age and older; 2) Fluzone High Dose Quadrivalent (IIV4-HD) may be considered an option for individuals 65 years of age and older who are currently recommended to receive Fluzone® High Dose (trivalent); and 3) Flucelvax® Quad may be considered amongst the quadrivalent influenza vaccines offered to adults and children nine years of age and older for annual influenza immunization. Guidance for use of influenza immunizations during the coronavirus disease 2019 pandemic is also highlighted. Conclusion: NACI continues to recommend that an age-appropriate influenza vaccine should be offered annually to anyone six months of age and older who does not have contraindications to the vaccine. Vaccination should be offered as a priority to people at high risk of influenza-related complications or hospitalization, people capable of transmitting influenza to those at high risk of complications, and others as indicated.

scholarly journals High-dose trivalent influenza vaccine: safety and immunogenicity

2020 ◽  
Author(s):  
Raúl Ortiz de Lejarazu ◽  
◽  
Federico Martinón Torres ◽  
Ángel Gil de Miguel ◽  
Javier Díez Domingo ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Influenza Vaccine ◽  
Randomized Clinical Trials ◽  
Standard Dose ◽  
Meta Analysis ◽  
Influenza Virus Infection ◽  
The Elderly ◽  
The United States ◽  
High Dose ◽  
Trivalent Influenza Vaccine

Adults aged 65 years or older suffer the most severe health effects of seasonal flu. Although the influenza vaccine is effective in preventing influenza virus infection and its complications, it is not as effective in the elderly due to age-associated immunosenescence phenomenon. Since 2009, a high-dose trivalent influenza vaccine has been approved in the United States for the immunization of people ≥ 65 years with an antigen concentration four times higher than the standard vaccine. Multiple clinical trials carried out over different seasons, and using different methodologies, have shown that the high-dose trivalent influenza vaccine is not only more effective, but it also has a similar safety profile and is more immunogenic than the standard dose vaccine in the prevention of flu and its complications in the elderly. This document reviews the current scientific evidence on the safety and immunogenicity of high-dose influenza vaccine in people aged 65 years and over, and includes information from randomized clinical trials, observational studies with data from real clinical practice, and systematic reviews, and meta-analysis.

scholarly journals Safety and effectiveness of dose-sparing strategies for intramuscular seasonal influenza vaccine: a rapid scoping review

BMJ Open ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. e050596
Author(s):  
Carole Lunny ◽  
Jesmin Antony ◽  
Patricia Rios ◽  
Chantal Williams ◽  
Naveeta Ramkissoon ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Scoping Review ◽  
Seasonal Influenza ◽  
Data Extraction ◽  
Grey Literature ◽  
Clinical Effectiveness ◽  
Influenza Vaccines ◽  
Cochrane Library ◽  
Healthy Humans ◽  
Dose Sparing

BackgroundThe objective of this rapid scoping review was to identify studies of dose-sparing strategies for administration of intramuscular seasonal influenza vaccines in healthy individuals of all ages.MethodsComprehensive literature searches were executed in MEDLINE, Embase and the Cochrane library. The grey literature was searched via international clinical trial registries for relevant studies published in English in the last 20 years. We included studies in healthy humans of any age that used any dose-sparing strategy to administer intramuscular seasonal influenza vaccines. Title/abstract and full-text screening were carried out by pairs of reviewers independently. Data extraction was conducted by a single reviewer and verified by a second reviewer. Our outcomes were influenza infections, intensive care unit admission, pneumonia, hospitalisations, adverse events and mortality. Results were summarised descriptively.ResultsA total of 13 studies with 10 351 participants were included in the review and all studies were randomised controlled trials (RCTs) conducted between 2006 and 2019. The most common interventions were the trivalent influenza vaccine (n=10), followed by the quadrivalent influenza vaccine (n=4). Nine studies included infants/toddlers 6–36 months old and one of these studies also included children and adolescents. In these nine studies, no clinical effectiveness outcomes were reported. Of the four adult studies (≥18 years), two studies reported on effectiveness outcomes, however, only one RCT reported on laboratory-confirmed influenza.ConclusionsDue to the low number of studies in healthy adults and the lack of studies assessing confirmed influenza and influenza-like illness, there remains a need for further evaluation.

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