High-dose Influenza Vaccine Research Articles

Summary of the National Advisory Committee on Immunization (NACI) Seasonal Influenza Vaccine Statement for 2024-2025.

The National Advisory Committee on Immunization (NACI) reviews the evolving evidence on influenza immunization and provides annual recommendations regarding the use of seasonal influenza vaccines. The NACI Statement on Seasonal Influenza Vaccine for 2024-2025 updates the NACI recommendations from the previous year. To summarize the 2024-2025 NACI seasonal influenza vaccine recommendations and to highlight new and updated information. For the development of the Statement on Seasonal Influenza Vaccine for 2024-2025, the NACI Influenza Working Group applied the NACI evidence-based process to assess available evidence and formulate recommendations. These recommendations underwent a thorough evaluation and were approved by NACI based on the available evidence. Key updates for the 2024-2025 influenza season include updated immunization recommendations reflecting changes in influenza epidemiology and revised guidance for vaccine administration during pregnancy and in older adults. The National Advisory Committee on Immunization recommends that any age-appropriate quadrivalent or trivalent influenza vaccine should be used for individuals six months of age and older who do not have contraindications or precautions. NACI reaffirms the importance of influenza vaccination with inactivated or recombinant influenza vaccines in pregnancy. Finally, NACI recommends that inactivated high-dose (IIV-HD), inactivated adjuvanted (IIV-Adj) or recombinant influenza vaccine (RIV) should be offered, when available, over other influenza vaccines for adults 65 years of age and older.

Summary of the National Advisory Committee on Immunization (NACI) Supplemental Guidance on Influenza Vaccination in Adults 65 Years of Age and Older.

Adults 65 years of age and older are at higher risk of influenza complications, such as hospitalization and death. As a result, seasonal influenza immunization is particularly important for this group. This supplemental statement provides an evidence summary on the preferential use of one or more of the age-appropriate influenza vaccines for adults 65 years of age and older, over other age-appropriate influenza vaccines. The National Advisory Committee on Immunization (NACI)'s Influenza Working Group undertook an overview of existing systematic reviews on the efficacy, effectiveness, safety and cost effectiveness of influenza vaccination in adults 65 years of age and older. Additionally, NACI's evidence-based process was used to assess the quality of eligible studies, summarize and analyze the findings and apply an ethics, feasibility and acceptability lens to develop recommendations. The evidence suggests that high-dose inactivated influenza vaccine (IIV-HD), adjuvanted inactivated influenza vaccine (IIV-Adj) and recombinant influenza vaccine (RIV) offer increased benefits for adults 65 years of age and older when compared to standard dose influenza vaccines. The IIV-HD had the most supporting evidence, followed by IIV-Adj and then RIV. Evidence comparing these enhanced vaccines was limited. Following a thorough review of the complete body of evidence, NACI recommends that IIV-HD, IIV-Adj or RIV should be offered over other influenza vaccines for adults 65 years of age and older. NACI also continues to strongly recommend the inclusion of adults 65 years of age and older among those for whom it is particularly important to receive influenza vaccination.

Effect of high-dose vs. standard-dose quadrivalent influenza vaccine on death and hospitalizations in older adults with cardiovascular disease: a prespecified analysis of the DANFLU-1 study

Abstract Background The results of the DANFLU-1 trial indicated that high-dose quadrivalent influenza vaccines (HDQIV) as compared to standard-dose quadrivalent influenza vaccines (SDQIV) may reduce the incidence of death and hospitalization with pneumonia or influenza in older adults. Whether this effect differs by the presence of cardiovascular disease is unknown. Purpose To conduct a prespecified analysis aimed at assessing whether the presence of cardiovascular disease at baseline modified the effect of HDQIV vs SDQIV on clinical outcomes in the DANFLU-1 trial. Methods DANFLU-1 was a pragmatic, open-label trial randomizing 12,477 adults aged 65-79 years 1:1 to HDQIV vs SDQIV during the 2021/2022 influenza season. The trial used the Danish nationwide registers to collect both baseline and outcome data. Participants were included in October and November of 2021 and follow-up ended on May 31, 2022. In this prespecified analysis, we assessed the effectiveness of HDQIV vs SDQIV on clinical endpoints according to the presence of cardiovascular disease at baseline and across different cardiovascular subgroups including ischemic heart disease, heart failure and atrial fibrillation. Effectiveness was assessed with Cox proportional hazards regression. In addition, hospitalizations were also assessed with recurrent event analysis using negative binomial regression. Results The mean age of the 12,477 participants in the DANFLU-1 trial was 71.7 years (SD 3.9) and 6600 (53%) were male. During a median follow-up of 237 days (interquartile range 232-239 days), 62 participants died (0.5%), 38 (0.3%) were hospitalized with pneumonia or influenza, 220 (1.8%) were hospitalized with a cardiorespiratory diagnosis, and 192 (1.5%) were hospitalized with a cardiovascular diagnosis. HDQIV was associated with a lower incidence of death during follow-up as compared with SDQIV (HR 0.51 [95% CI 0.30-0.86], p=0.012), and this effect was consistent in participants with CVD and without CVD and across cardiovascular subgroups (Figure 1). HDQIV was also associated with a lower incidence of hospitalization with pneumonia or influenza (IRR 0.30 (95% CI 0.14-0.64, p=0.002), and this effect was consistent irrespective of CVD (subgroup estimates were inestimable due to low power) (Figure 2). There was no difference in the incidence of cardiorespiratory or cardiovascular hospitalization between the HDQIV and SDQIV group. No significant effect modification by the presence of CVD or cardiovascular subgroups was observed (Figure 1 and 2). Conclusions In this prespecified analysis of the DANFLU-1 randomized trial, high-dose influenza vaccine was associated with a reduced rate of death and hospitalization with influenza or pneumonia and this effect was consistent in participants with CVD and across cardiovascular subgroups.Figure 1:Time to event analysisFigure 2:Recurrent event analysis

Relative effectiveness of high-dose versus standard-dose quadrivalent influenza vaccine against hospitalizations and mortality according to frailty score: a post-hoc analysis of the DANFLU-1 trial

Abstract Background Frailty is a major risk factor for adverse cardiovascular events. Influenza vaccination has been shown to protect against cardiovascular fatal and nonfatal events. However, limited data exist on the added benefit of high-dose versus standard-dose influenza vaccination according to frailty status. Purpose We sought to assess the relative effectiveness of high-dose (QIV-HD) versus standard-dose (QIV-SD) quadrivalent influenza vaccination according to frailty status in elderly individuals. Methods This is a post-hoc analysis of the randomized controlled feasibility trial of QIV-HD versus QIV-SD conducted during the 2021–2022 influenza season in adults aged 65–79 years. We assessed the following prespecified outcomes: hospitalizations for pneumonia or influenza, cardio-respiratory hospitalizations, cardiovascular hospitalizations, all-cause hospitalizations and all-cause mortality. Level of frailty was defined according to the Hospital Frailty Risk Score based on ICD-10 codes for relevant comorbidities any time prior to vaccination. We divided the participants into two categories according to Frailty Score (FS): low frailty (0-4 points) and intermediate or high frailty (≥5 points). We analyzed outcomes as time to first event using Cox proportional hazards regression. Results Among 12,473 randomly assigned participants to QIV-HD versus QIV-SD (mean age 71.7 years, 47.1% female), 10,711 (85.9%) were categorized as having low frailty and 1,762 (14.1%) had intermediate or high frailty. In total, 38 individuals were hospitalized for pneumonia or influenza during follow-up, 219 were hospitalized for cardiorespiratory illness, 1055 were hospitalized due to any cause and 62 died during follow-up. FS significantly modified the effect of QIV-HD versus QIV-SD for all-cause mortality (P for interaction 0.02). In participants with low frailty, QIV-HD was associated with a lower risk of all-cause mortality (Figure 1: HR 0.26, 95% CI 0.13 to 0.55), whereas there was no evidence of effect among those with intermediate or high frailty (HR 1.68, 95% CI 0.66 to 4.26). QIV-HD versus QIV-SD was associated with a lower incidence of hospitalizations for pneumonia and influenza, this effect was consistent regardless of frailty status (P for interaction 0.88). QIV-HD was not associated with a significantly lower incidence of hospitalizations due to cardiovascular, cardiorespiratory or respiratory disease or any cause regardless of frailty status. Conclusions In this post-hoc analysis of a large-scale pragmatic trial, QIV-HD was similarly associated with a lower incidence of hospitalizations for pneumonia and influenza among older adults irrespective of frailty status. The potential benefit of QIV-HD versus QIV-SD may therefore be applicable regardless of frailty status. However, our results suggest that QIV-HD is associated with a lower risk of all-cause mortality among adults with low frailty only.Figure 1.

Relative effectiveness of high-dose vs. standard-dose quadrivalent influenza vaccine according to time of day of vaccination: a post-hoc analysis of the DANFLU-1 randomised clinical trial

Abstract Background Circadian variations have been shown to affect antibody response following vaccination. We sought to evaluate whether time of day of vaccination (ToV) modified the relative effectiveness of high-dose (QIV-HD) vs. standard-dose (QIV-SD) quadrivalent influenza vaccination, and further whether ToV was independently associated with hospitalisations and mortality. Methods This is a post-hoc analysis of the DANFLU-1 trial which was a randomized trial of QIV-HD vs. QIV-SD in adults aged 65-79 years conducted during the 2021-2022 influenza season. Vaccination took place between 7:05 AM and 8:08 PM. For this study, we stratified participants into early and late vaccination groups according to ToV before or after 11 AM, respectively. Prespecified outcomes included hospitalisations for pneumonia or influenza, respiratory disease, cardiovascular disease, and cardio-respiratory disease as well as all-cause hospitalisations and mortality. Hospitalisations were analysed as recurrent events using negative binomial regression, while mortality was analysed using Cox proportional hazard models, both of which were also used to test for interaction. For multivariable analysis, models were adjusted for baseline risk factors including sex, age, and multiple lung diseases. ToV was furthermore assessed as a continuous variable with 2-hour increments. Results In the final study population, the early group consisted of 5,371 (43%) participants (mean age 71.6±3.9 years, male sex 53.6%, QIV-SD 50.1%), while the late group consisted of 7,106 (57%) (mean age 71.8±4.0 years, male sex 52.4%, QIV-HD 49.9%). During follow-up, we observed 43 hospitalisations for pneumonia or influenza, 76 respiratory hospitalisations, and 62 mortalities. In recurrent event analysis, QIV-HD was associated with lower incidence of hospitalisation for pneumonia or influenza compared with QIV-SD irrespective of whether administered early (IRR 0.17 (95% CI 0.03-0.86), p=0.032) or late (IRR 0.37 (95% CI 0.16-0.88), p=0.024) (p-value for interaction = 0.69) (Figure 1). Effect estimates were consistent for all outcomes excluding cardiovascular hospitalisations regardless of early or late vaccination, and no effect modification was found (Figure 1). Interestingly, late vaccination was associated with higher incidence rate of respiratory hospitalisation (IRR 3.00 (95% CI 1.13-7.98), p=0.024, Figure 2), irrespective of vaccine type. The same association was found for ToV as a continuous variable (IRR 1.28 per 2-hour increment (95% CI 1.02-1.60), p=0.035). All above associations remained significant in multivariable analysis. Conclusion QIV-HD was associated with lower incidence of hospitalisation for pneumonia or influenza regardless of time of day for vaccination. In addition, later vaccination was associated with higher incidence of respiratory hospitalisation independent of vaccine type and known risk factors. Due to low power, however, this finding should be regarded as exploratory.Figure 1:Forest plotFigure 2:Incidence rates

Similar humoral responses but distinct CD4+ T cell transcriptomic profiles in older adults elicited by MF59 adjuvanted and high dose influenza vaccines.

Older age (≥ 65 years) is associated with impaired responses to influenza vaccination, leading to the preferential recommendation of MF59-adjuvanted (MF59Flu) or high-dose (HDFlu) influenza vaccines for this age group in the United States. Herein, we characterized transcriptomic profiles of CD4+ T cells isolated from 234 recipients (≥ 65 years) of either MF59Flu or HDFlu vaccine, prior to vaccination and 28 days thereafter. We identified 412 and 645 differentially expressed genes (DEGs) in CD4+ T cells of older adults after receiving MF59Flu and HDFlu, respectively. DEGs in CD4+ T cells of MF59Flu recipients were enriched in 14 KEGG pathways, all of which were downregulated. DEGs in CD4+ T cells of HDFlu recipients were enriched in 11 upregulated pathways and 20 downregulated pathways. CD4+ T cells in both vaccine groups shared 50 upregulated genes and 75 downregulated genes, all of which were enriched in 7 KEGG pathways. The remaining 287 and 520 DEGs were specifically associated with MF59Flu and HDFlu, respectively. Unexpectedly, none of these DEGs was significantly correlated with influenza A/H3N2-specific HAI titers, suggesting these DEGs at the individual level may have a limited role in protection against influenza. Our findings emphasize the need for further investigation into other factors influencing immunity against influenza in older adults.

Comparison of immunogenicity of adjuvanted and high dose influenza vaccination in long-term care facility residents.

The CDC recommends the more immunogenic adjuvanted and high-dose flu vaccines over standard-dose, non-adjuvanted vaccines for individuals above 65 years old. The current study compares adjuvanted trivalent inactivated flu vaccine (aTIV, FLUAD) versus high-dose flu vaccine (HD-IIV3, FLUZONE HD) to determine if they met non-inferiority standards for older long-term care facility (LTCF) residents. We collected blood from long-term care facility residents participating in a randomized 1:1 active control trial comparing MF59C.1 adjuvanted trivalent inactivated flu vaccine, aTIV versus HD-IIV3 over the course of two flu seasons, 2018-2019 and 2019-2020 (Trial, NCT03694808). We assessed humoral immunity at set time points via hemagglutinin inhibition assays (HAI) and anti-neuraminidase (enzyme-linked lectin assays (ELLA)). The recombinant influenza vaccine (RIV, Flublok) was assessed similarly in year two for a small number of participants who were carried over from year 1 (n=32). We enrolled 387 volunteers and administered either aTIV (n=194), HD-IIV3 (n=193) over the course of the 2018-2019 and 2019-2020 flu seasons. Among those enrolled and randomized in year one, a subset were administered RIV and studied in year two (n = 32). At 28 days post-vaccination, aTIV exhibited non-inferiority to HD-IIV3 for HAI for both H1N1 and H3N2 strains (GMT ratios (95% CI) for HD-IIV3/aTIV of 1.03(0.76, 1.4) and 1.04(0.73, 1.48), respectively; both 95% CI upper bounds < 1.5 to meet non-inferiority criteria) but not for Influenza B (GMT ratio (95% CI) = 1.21 (0.91, 1.61)). Non-inferiority criteria for HAI seroconversion were not met for any of the three strains. Applying the same non-inferiority criteria to neuraminidase inhibition (NI), both day 28 titer and seroconversion in aTIV were non-inferior to HD-IIV3 for H1N1 and H3N2 strains. Both aTIV and HD-IIV3 elicited similar immune responses with robust antibody responses. For the primary outcome, aTIV is non-inferior to HD-IIV3 for HAI titer of H1N1 and H3N2 but failed to meet non-inferiority criteria for Influenza B and seroconversion for all assessed strains. For the secondary outcome, aTIV was non-inferior to HD-IIV3 for both titer and seroconversion of anti-neuraminidase for both H1N1 and H3N2.

Safety of Simultaneous Vaccination With Adjuvanted Zoster Vaccine and Adjuvanted Influenza Vaccine

Quadrivalent adjuvanted inactivated influenza vaccine (aIIV4) and adjuvanted recombinant zoster vaccine (RZV) contain novel adjuvants. Data are limited on the comparative safety, reactogenicity, and health-related quality of life (HRQOL) effects of the simultaneous administration of these vaccines. To compare the safety and reactogenicity after simultaneous doses of RZV and aIIV4 administration (opposite arms) with simultaneous doses of RZV with quadrivalent high-dose inactivated influenza vaccine [HD-IIV4]). This randomized blinded clinical trial was conducted during the 2021-2022 and 2022-2023 influenza seasons at 2 centers in the US among community-dwelling adults aged 65 years or older. Analysis was performed on an intention-to-treat basis. Simultaneous intramuscular administration of RZV dose 1 and aIIV4 or HD-IIV4 in opposite arms after age stratification (65-69 and ≥70 years) and randomization. The primary outcome was the proportions of participants with 1 or more severe solicited reactions during days 1 to 8, using a noninferiority test (10% noninferiority margin). Additional measures included serious adverse events and adverse events of clinical interest during days 1 to 43 of the study period. A total of 267 adults (median age, 71 years [range, 65-92 years]; 137 men [51.3%]) were randomized; 130 received simultaneous RZV and aIIV4, and 137 received simultaneous RZV and HD-IIV4. The proportion of patients reporting 1 or more severe reactions after simultaneous administration of RZV and aIIV4 (15 of 115 [11.5%]) was noninferior compared with simultaneous RZV and HD-IIV4 (17 of 119 [12.5%]) (absolute difference, -1.0% [95% CI, -8.9% to 7.1%]). There were no significant differences in the number of serious adverse events or adverse events of clinical interest between the groups. In this clinical trial of simultaneous doses of RZV and aIIV4 compared with simultaneous doses of RZV and HD-IIV4, overall safety findings were similar between groups. From a safety standpoint, this study supports the simultaneous administration of RZV and aIIV4 among older adults. ClinicalTrials.gov Identifier: NCT05007041.

Immunogenicity and Reactogenicity of High-dose or Standard-dose Influenza Vaccine in a Second Consecutive Influenza Season.

Pediatric hematopoietic cell transplant (HCT) recipients are at high-risk for morbidity from influenza virus infection. We demonstrated in a primary phase II randomized controlled trial that two post-HCT doses of high-dose trivalent influenza vaccine (HD-TIV) given four weeks apart were more immunogenic than two doses of standard-dose quadrivalent influenza vaccine (SD-QIV). Herein, we present immunogenicity and safety of influenza vaccination in a consecutive season post-HCT using the same dosing regimen. A subcohort of study participants re-enrolled and had hemagglutinin inhibition (HAI) titers measured at baseline and four weeks after each vaccine dose in year two. We estimated geometric mean fold rise (GMFR) in HAI titer from baseline for each group and used linear mixed effects models to estimate adjusted geometric mean ratios (aGMR, comparing HD-TIV to SD-QIV) for each antigen at each time point. We described systemic and injection-site reactions. A total of 65 subcohort patients participated (33 SD-QIV, 32 HD-TIV). Post-vaccine GMFR and aGMR estimates were higher for both groups following a single influenza vaccine dose in year two compared to two doses of the same formulation in year one. Both groups had similar frequencies of injection-site and systemic reactions. A single dose of HD-TIV or SD-QIV was more immunogenic in year two than two doses of the same formulation in year one. Reactogenicity was comparable between groups. One dose of influenza vaccine may be sufficient after a two-dose schedule in the prior year post-HCT.

Protection against influenza hospitalizations from enhanced influenza vaccines among older adults: A systematic review and network meta-analysis.

Influenza vaccines are available to help protect persons aged ≥65 years, who experience thousands of influenza hospitalizations annually. Because some influenza vaccines may work better than others, we sought to assess benefit of high-dose (HD), adjuvanted (ADJ), and recombinant (RIV) influenza vaccines ("enhanced influenza vaccines") compared with standard-dose unadjuvanted influenza vaccines (SD) and with one another for prevention of influenza-associated hospitalizations among persons aged ≥65 years. We searched MEDLINE, Embase, CINAHL, Scopus, and Cochrane Library to identify randomized or observational studies published between January 1990 and October 2023 and reporting relative vaccine effectiveness (rVE) of HD, ADJ, or RIV for prevention of influenza-associated hospitalizations among adults aged ≥65 years. We extracted study data, assessed risk of bias, and conducted random-effects network meta-analysis and meta-regression. We identified 32 studies with 90 rVE estimates from five randomized and 27 observational studies (71,459,918 vaccinated participants). rVE estimates varied across studies and influenza seasons. Pooled rVE from randomized studies was 20% (95% CI -54 to 59) and 25% (95% CI -19 to 53) for ADJ and HD compared with SD, respectively; rVE was 6% (95% CI -109 to 58) for HD compared with ADJ; these differences were not statistically significant. In observational studies, ADJ, HD, and RIV conferred modestly increased protection compared with SD (rVE ranging from 10% to 19%), with no significant differences between HD, ADJ, and RIV. With enhanced vaccines combined, rVE versus SD was 18% (95% CI 3 to 32) from randomized and 11% (95% CI 8 to 14) from observational evidence. Meta-regression of observational studies suggested that those requiring laboratory confirmation of influenza reported greater benefit of enhanced vaccines. HD, ADJ, and RIV provided stronger protection than SD against influenza hospitalizations among older adults. No differences in benefit were observed in comparisons of enhanced influenza vaccines with one another.

Time of day for vaccination, outcomes, and relative effectiveness of high-dose vs. standard-dose quadrivalent influenza vaccine: A post hoc analysis of the DANFLU-1 randomized clinical trial

Morning influenza vaccination enhances antibody response. In this post hoc analysis of the DANFLU-1 trial, we sought to evaluate the association between time of day for vaccination (ToV) and outcomesand whether ToV modified the relative effectiveness of high-dose (QIV-HD) vs. standard-dose (QIV-SD) quadrivalent influenza vaccine. DANFLU-1 was a pragmatic feasibility trial of QIV-HD vs. QIV-SD. Outcomes included hospitalizations and mortality. For subgroup analysis, the population was dichotomized at median ToV into two groups (early and late). The study population included 12,477 participants. Mean age was 71.7±3.9 years with 5877 (47.1%) female participants. Median ToV was 11.29AM. Earlier ToV was associated with fewer respiratory hospitalizations independent of vaccine type, which persisted in adjusted analysis (IRR 0.88 per 1-hour decrement (95% CI 0.78- 0.98, p=0.025). No effect modification by continuous or dichotomous ToV was found. In subgroup analysis, effects consistently favored QIV-HD against hospitalizations for pneumonia or influenza (early: IRR 0.30; late: 0.29), all-cause hospitalizations (early: IRR 0.87; late: 0.86), and mortality (early: HR 0.53; late: 0.50). In this exploratory post hoc analysis, earlier ToV was associated with fewer respiratory hospitalizations. The relative effectiveness of QIV-HD vs. QIV-SD was not modified by ToV. Further research is needed to confirm findings. Clinicaltrials.gov: NCT05048589.

Relative Effectiveness of High-Dose vs. Standard-Dose Quadrivalent Influenza Vaccine in Older Adults with Cardiovascular Disease: A Prespecified Analysis of the DANFLU-1 Randomized Clinical Trial.

Background: Influenza vaccination reduces the risk of adverse outcomes in patients with cardiovascular disease (CVD). We sought to evaluate whether the presence of CVD modified the relative effectiveness of high-dose (QIV-HD) vs. standard-dose (QIV-SD) quadrivalent influenza vaccine in this prespecified analysis of the DANFLU-1 trial. Methods: DANFLU-1 was a pragmatic, open-label, randomized feasibility trial of QIV-HD vs. QIV-SD in adults aged 65-79 years during the 2021/2022 influenza season in Denmark. Vaccines were allocated in a 1:1 ratio. Baseline and follow-up data regarding diagnoses and mortality were obtained from Danish national registers. The trial is registered at Clinicaltrials.gov: NCT05048589. The CVDs assessed included heart failure (HF), ischemic heart disease (IHD), atrial fibrillation, and a combined group denoted "chronic CVD" consisting of the aforementioned diseases, among others. Prespecified outcomes included hospitalizations for pneumonia or influenza, respiratory disease, CVD, cardiorespiratory disease, all-cause hospitalizations, and mortality. Effect modification was tested using interaction terms. Results: The final study population included 12,477 participants (mean age 71.7±3.9 years, 5,877 (47.1%) female), of whom 2,540 (20.4%) had chronic CVD. QIV-HD vs. QIV-SD was associated with a lower incidence of hospitalizations for pneumonia or influenza (IRR 0.30 (95%-CI 0.14-0.64)) and all-cause mortality (IRR 0.51 (0.30-0.86)) regardless of chronic CVD (p for interaction=0.57 and 0.49, respectively). The relative effectiveness of QIV-HD vs. QIV-SD against all-cause hospitalizations was modified in participants with chronic CVD (Overall: IRR 0.87 (0.76-0.99); no chronic CVD: 0.79 (0.67-0.92); chronic CVD: 1.11 (0.88-1.39); p for interaction=0.026). No other effect modification was observed by the presence of chronic CVD, HF, IHD, or atrial fibrillation. Conclusions: The relative effectiveness of QIV-HD vs. QIV-SD was consistent against hospitalizations for pneumonia or influenza and all-cause mortality regardless of chronic CVD. However, the relative effectiveness against all-cause hospitalizations was modified by the presence of chronic CVD. These results should be considered hypothesis-generating.

High-Dose vs Standard-Dose Influenza Vaccine in Chronic Kidney Disease: A Secondary Analysis of DANFLU-1

High-Dose vs Standard-Dose Influenza Vaccine in Chronic Kidney Disease: A Secondary Analysis of DANFLU-1

The relative effectiveness of a high-dose quadrivalent influenza vaccine versus standard-dose quadrivalent influenza vaccines in older adults in France: a retrospective cohort study during the 2021–2022 influenza season

ObjectivesHigh-dose quadrivalent influenza vaccine (HD-QIV) was introduced during the 2021/2022 influenza season in France for adults aged ≥65 years as an alternative to standard-dose quadrivalent influenza vaccine (SD-QIV). The aim of this study is to estimate the relative vaccine effectiveness of HD-QIV vs. SD-QIV against influenza-related hospitalizations in France. MethodsCommunity-dwelling individuals aged ≥65 years with reimbursed influenza vaccine claims during the 2021/2022 influenza season were included in the French national health insurance database. Individuals were followed up from vaccination day to 30 June 2022, nursing home admission or death date. Baseline socio-demographic and health characteristics were identified from medical records over the five previous years. Hospitalizations for influenza and other causes were recorded from 14 days after vaccination until the end of follow-up. HD-QIV and SD-QIV vaccinees were matched using 1:4 propensity score matching with an exact constraint on age group, sex, week of vaccination, and region. Incidence rate ratios were estimated using zero-inflated Poisson or zero-inflated negative binomial regression models. ResultsWe matched 405 385 HD-QIV to 1 621 540 SD-QIV vaccinees. HD-QIV was associated with a 23.3% (95% CI, 8.4–35.8) lower rate of influenza hospitalizations compared with SD-QIV (69.5/100 000 person years vs. 90.5/100 000 person years). Post-matching, we observed higher rates in the HD-QIV group for hospitalizations non-specific to influenza and negative control outcomes, suggesting residual confounding by indication. DiscussionHD-QIV was associated with lower influenza-related hospitalization rates vs. SD-QIV, consistent with existing evidence, in the context of high SARS-CoV-2 circulation in France and likely prioritization of HD-QIV for older/more comorbid individuals.

Viral infection after hematopoietic stem cell transplantation.

Viral infections are important complications after allogeneic hematopoietic stem cell transplantation. New infections develop such as SARS-CoV-2 with the potential for severe consequences. In this review, newly published information regarding management of viral infections is discussed. Letermovir and maribavir are antiviral agents that have positively impacted the management of cytomegalovirus infections. These should today be included in treatment algorithms. The first antiviral cellular therapy for anti-CD20 refractory EBV-associated lymphoproliferative disease is now licensed and available. Vaccination as well as introduction of antiviral agents, mAbs and possibly the development of different viral strains have reduced mortality in COVID-19 in this patient population. Well designed studies have shown the improved immunogenicity of high-dose influenza vaccines. There is still an unmet medical need for patients infected with human metapneumovirus and parainfluenza viruses. Although improvements in patient management for several important posttransplantation viral infections have been reported, an unmet medical need still exists for other viruses occurring in this high-risk population.

Relative Effectiveness of the MF59-Adjuvanted Influenza Vaccine Versus High-Dose Influenza Vaccine in Older Adults With Influenza Risk Factors During the 2019-2020 US Influenza Season.

This study estimated the relative vaccine effectiveness (rVE) of the MF59-adjuvanted trivalent influenza vaccine (aTIV) versus high-dose trivalent inactivated influenza vaccine (HD-TIV) for prevention of influenza-related medical encounters (IRMEs) during the 2019-2020 United States (US) influenza season stratified by the cumulative number of influenza risk factors. A secondary objective evaluated outpatient IRMEs and influenza- and pneumonia-related hospitalizations. This retrospective cohort study included US adults ≥65 years old vaccinated with aTIV or HD-TIV between 1 August 2019 and 31 January 2020. Electronic health records linked to claims were used to ascertain exposure, covariates, risk factors, and outcomes. Multivariable adjusted odds ratios (ORs) were derived using inverse probability of treatment-weighted samples to calculate rVEs independently for individuals with 0, ≥1, 1-2, or ≥3 risk factors. The study included 1 115 725 aTIV and 2 561 718 HD-TIV recipients. For the primary outcome of any IRME, the analysis found comparable effectiveness between aTIV and HD-TIV (rVE, 5.2% [95% confidence interval {CI}, -5.9% to 15.1%]) among those with 0 risk factors, whereas aTIV was more effective than HD-TIV among patients with ≥1, 1-2, or ≥3 risk factors (12.5% [95% CI, 10.0%-15.0%], 18.4% [95% CI, 13.7%-22.9%], and 10.4% [7.4%-13.3%], respectively). The same trends were observed for the secondary outcomes. This study demonstrated comparable effectiveness of aTIV and HD-TIV among individuals with no identified risk factors and higher effectiveness of aTIV compared with HD-TIV in preventing any IRMEs, outpatient IRMEs, and influenza- or pneumonia-related hospitalizations among those with at least 1 or multiple high-risk factors in adults ≥65 years old.

Trivalent and quadrivalent seasonal influenza vaccine in adults aged 60 and older: a systematic review and network meta-analysis

ObjectivesTo compare the efficacy of influenza vaccines of any valency for adults 60 years and older.Design and settingSystematic review with network meta-analysis (NMA) of randomised controlled trials (RCTs). MEDLINE, EMBASE,...

Cost-effectiveness of recombinant influenza vaccine compared with standard dose influenza vaccine in adults 18–64 years of age

BackgroundThe Advisory Committee on Immunization Practices (ACIP) uses the Evidence to Recommendations Framework that includes cost-effectiveness analyses (CEA) for determining vaccine recommendations. ACIP’s preference for protecting adults ≥ 65 years is enhanced vaccines, including recombinant influenza vaccine (RIV4), adjuvanted or high dose influenza vaccine. Less is known about the CEA of enhanced vaccines for younger adults. MethodsWe used decision analysis modeling from a societal perspective to determine the cost-effectiveness, measured in quality adjusted life years (QALYs), of RIV4 compared with standard dose quadrivalent influenza vaccine (SD-IIV4) in adults 18–64 years old. Model inputs included 2018–2020 vaccine effectiveness (VE) estimates based on medical record data from a large local health system, 2019–2020 national vaccination and influenza epidemic parameters, with costs and population distributions fitted to the season. ResultsAmong adults ages 18–64 years, RIV4 cost $94,186/QALY gained, compared to SD-IIV4. Among those 50–64 years old, RIV4 was relatively more cost-effective ($61,329/QALY gained). Cost-effectiveness estimates for 18–64-year-olds were sensitive to the absolute difference in VE between SD-IIV4 and RIV4, among other parameters. Use of RIV4 in 18–64-year-olds would result in fewer cases (669,984), outpatient visits (261,293), hospitalizations (20,046) and deaths (1,018) annually. The majority (59 %; 597 of 1018) of the decreases in deaths occurred in the 50–64-year-olds. ConclusionsWhile RIV4 was effective and cost-effective relative to SD-IIV4 for both 50–64-year-old and 18–64-year-old adults, cost-effectiveness was sensitive to small changes in parameters among 18–64-year-olds. Because substantial public health benefits occur with enhanced vaccines, health systems and policy makers may opt for preferential product use in select age/risk groups (e.g., 50–64 year olds) to maximize their cost-benefit ratios.

Relative vaccine effectiveness of MF59-adjuvanted vs high-dose trivalent inactivated influenza vaccines for prevention of test-confirmed influenza hospitalizations during the 2017–2020 influenza seasons

ObjectivesThis study evaluated relative vaccine effectiveness (rVE) of MF59-adjuvanted trivalent inactivated influenza vaccine (aTIV) vs high-dose trivalent inactivated influenza vaccine (HD-TIV) for prevention of test-confirmed influenza emergency department visits and/or inpatient admissions (“ED/IP”) and for IP admissions alone pooled across the 2017–2020 influenza seasons. Exploratory individual season analyses were also performed. MethodsThis retrospective test-negative design study included United States (US) adults age ≥65 years vaccinated with aTIV or HD-TIV who presented to an ED or IP setting with acute respiratory or febrile illness during the 2017–2020 influenza seasons. Test-positive cases and test-negative controls were grouped by vaccine received. The rVE of aTIV vs HD-TIV was evaluated using a combination of inverse probability of treatment weighting and logistic regression to adjust for potential confounders. ResultsPooled analyses over the three seasons found no significant differences in the rVE of aTIV vs HD-TIV for prevention of test-confirmed influenza ED/IP (−2.5% [−19.6, 12.2]) visits and admissions or IP admissions alone (−1.6% [−22.5, 15.7]). The exploratory individual season analyses also showed no significant differences. ConclusionsEvidence from the 2017–2020 influenza seasons indicates aTIV and HD-TIV are comparable for prevention of test-confirmed influenza ED/IP visits in US adults age ≥65 years.

Protecting the elderly from influenza in the context of immune system senescence. Elderly aged 65 and over are vulnerable to influenza and its associated complications.: Position paper by the Romanian Society of Gerontology and Geriatrics.

Influenza affects millions globally each year, often causing severe complications, hospitalizations, and deaths, particularly among the elderly. As the global population ages, infections will pose a growing health risk. Annual vaccination remains the most effective way to prevent influenza and its complications. After the age of 65, people suffering from chronic diseases become the majority of this population category. All the data support that most of the population over 65 years old, whose immune system goes through immunosenescence, presents multimorbidity, requiring age-appropriate anti-influenza protection. The immune response to the traditional influenza vaccine has been proven to be lower in the elderly, highlighting the need for a more immunogenic vaccine specifically tailored to the elderly population group. Therefore, high-dose (HD) influenza vaccines have demonstrated their safety and are more effective in preventing influenza and its associated complications compared to standard-dose (SD) vaccines in the elderly in the context of immunosenescence. These recommendations focus on the safety, effectiveness, and efficacy of HD influenza vaccines, adapted to the elderly and available on the Romanian market, to increase the vaccination rate and, thus, protect against influenza infection and its complications. Therefore, strategies such as increased accessibility and free immunizations, as well as ensuring that flu vaccines for the elderly are prescribed without restrictions based on the number of comorbidities, should be used.