Adverse events of interest vary by influenza vaccine type and brand: Sentinel network study of eight seasons (2010–2018)

BackgroundInfluenza contributes significantly to the burden of disease worldwide; the United Kingdom has a policy of vaccination across all ages. Influenza vaccinations are known to be associated with common minor adverse events of interest (AEIs). The European Medicines Agency (EMA) recommends ongoing surveillance of AEIs following influenza vaccination to monitor common and detect infrequent but important AEIs.MethodsA retrospective cohort study using computerised medical record data from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) sentinel network database 2010–2018 (N = 848,375). We extracted data about vaccine exposure (n = 3,121,334) and consultations for AEIs within seven days of receiving vaccinations specified by the EMA (1,488,870 consultations by 430,029 unique individuals). We used a self-case series design which employs a likelihood estimation method using conditioning of observed adverse events. Such a model assumes non-homogenous Poisson intensity processes for each exposure period and age interval. We compared AEI between QIV and TIV reporting relative incidence (RI) of AEIs. A RI < 1 signified lower AEI rate compared to TIV.ResultsQIV was associated with a RI of AEIs of 1.14 (95%CI, 1.10–1.18, p < 0.01), though the number of years exposure was limited. By way of contrast, LAIV had a lower rate 0.60 (95%CI 0.63–0.68, p < 0.001). Cellular manufacture was also associated with a lower rate 0.78 (95%CI 0.61–0.99, p = 0.04). AEIs varied by season: Rash and musculoskeletal conditions are particularly pronounced in the 2014/15 season and respiratory conditions in 2016/17. In an analysis of all seasons, we found an elevated relative incidence of AEIs of 1.78 (95%CI, 1.62–1.95) in pregnant women and 1.76 (95%CI, 1.56 – 1.99) in children under 5 years.ConclusionRoutine sentinel network data can be used to contrast AEIs between vaccine types and may provide a consistent method of observation of vaccine benefit-risk over time.     

Immunogenicity and safety of MF59-adjuvanted quadrivalent influenza vaccine versus standard and alternate B strain MF59-adjuvanted trivalent influenza vaccines in older adults

ObjectiveEvaluate whether adjuvanted quadrivalent influenza vaccine (aQIV) elicits a noninferior immune response compared with a licensed adjuvanted trivalent influenza vaccine (aTIV-1; Fluad™) and aTIV-2 containing an alternate B strain, examine whether aQIV had immunological superiority for the B strain absent from aTIV comparators, and evaluate reactogenicity and safety among adults ≥65 years.MethodsIn a multicenter, double-blind, randomized controlled trial, adults ≥65 years were randomized 2:1:1 to vaccination with aQIV (n = 889), aTIV-1 (n = 445), or aTIV-2 (n = 444) during the 2017-2018 influenza season. Immunogenicity was assessed by hemagglutination inhibition (HI) assay conducted on serum samples collected before vaccination and 21 days after vaccination for homologous influenza strains.ResultsaQIV met non-inferiority criteria for geometric mean titer ratios (GMT ratios) and seroconversion rate (SCR) differences against aTIV. The upper bounds of the 2-sided 95% confidence interval (CI) for GMT ratios were <1.5 for all 4 strains (A/H1N1 = 1.27, A/H3N2 = 1.09, B-Yamagata = 1.08, B-Victoria = 1.08). The upper bounds of the 95% CI of the SCR differences were <10% for all 4 strains (A/H1N1 = 7.76%, A/H3N2 = 4.96%, B-Yamagata = 3.27%, B-Victoria = 2.55%). aQIV also met superiority criteria (upper bound of 95% CI for GMT ratios <1 and SCR differences <0) for B strain absent from aTIV comparators (B-Yamagata GMT ratio = 0.70, SCR difference = −8.81%; B-Victoria GMT ratio = 0.78, SCR difference = −8.11%). aQIV and aTIV vaccines were immunogenic and well-tolerated. The immunological benefit of aQIV was also demonstrated in age subgroups 65–74 years, 75–84 years, and ≥85 years and in those with high comorbidity risk scores. Reactogenicity profiles were generally comparable.ConclusionaQIV induces a similar immune response as the licensed aTIV vaccine against homologous influenza strains and has a comparable reactogenicity and safety profile. Superior immunogenicity against the additional B strain was observed, indicating that aQIV could provide a broader protection than aTIV against influenza in older adults (NCT03314662).     

Importance and value of adjuvanted influenza vaccine in the care of older adults from a European perspective – A systematic review of recently published literature on real-world data

BackgroundThere is an urgent need for improved influenza vaccines especially for older adults due to the presence of immunosenescence. It is therefore highly relevant to compare enhanced influenza vaccines with traditional influenza vaccines with respect to their effectiveness.ObjectiveTo compare vaccine efficacy and effectiveness of adjuvanted influenza vaccines (aTIV/aQIV) vs. non-adjuvanted standard-dose (TIV/QIV) and high-dose (TIV-HD/QIV-HD) influenza vaccines regarding influenza-related outcomes in older adults, complementing findings from the European Centre for Disease Prevention and Control (ECDC)’s systematic review of enhanced seasonal influenza vaccines from February 2020.MethodsA systematic literature search was conducted in Embase and MEDLINE to identify randomised controlled trials, observational studies and systematic reviews, published since ECDC’s systematic review (between 7 February 2020 and 6 September 2021). Included studies were appraised with either the Cochrane Risk of Bias tool, ROBINS-I or AMSTAR 2.ResultsEleven analyses from nine real-world evidence (RWE) studies comprising ～53 million participants and assessing the relative vaccine effectiveness (rVE) of aTIV vs. TIV, QIV and/or TIV-HD in adults aged ≥65 years over the 2006/07–2008/09 and 2011/12–2019/20 influenza seasons were identified. Nine analyses found that aTIV was significantly more effective than TIV and QIV in reducing influenza-related outcomes by clinical setting and suspected influenza outbreaks (rVE ranging from 7.5% to 25.6% for aTIV vs. TIV and 7.1% to 36.3% for aTIV vs. QIV). Seven analyses found similar effectiveness of aTIV vs. TIV-HD in reducing influenza-related medical encounters, inpatient stays and hospitalisations/emergency room visits. In three analyses, aTIV was significantly more effective than TIV-HD in reducing influenza-related medical encounters and office visits (rVE ranging from 6.6% to 16.6%). Risk of bias of identified studies was moderate to high.ConclusionsOur study suggests that both adjuvanted and high-dose vaccines are effective alternatives for vaccination programmes in older adults and preferable over conventional standard-dose vaccines.     

2011-2019年中国B型流感季节性、年龄特征和疫苗匹配度分析

目的 分析2011-2019年中国B型流感的季节性、年龄分布以及与疫苗的匹配程度,为今后B型流感的监测和疾病负担评价、四价流感疫苗应用、免疫策略制定提供证据。方法 利用全国流感监测网络2011年第14周至2019年第13周的流行病学和病原学监测数据,绘制热图、进行描述性统计,分析B型流感季节性和年龄分布特征。利用流感周报公布的抗原性分析结果,分析B型流感流行株与疫苗毒株的匹配情况。结果 2011-2019年中国B型流感呈现明显的季节性特征,在6个冬春季和A型共同流行,且B/Victoria和B/Yamagata系交替流行,部分南方地区在个别年度出现B型2个系共同流行。B型流感的年龄分布呈双峰,2个系的病毒均在5～15岁组阳性率最高,10岁为峰值;B/Victoria系病毒在25～35岁组为次高峰;B/Yamagata系病毒在55～65岁组为次高峰。B型流感流行株在2015-2016、2017-2018年度与三价流感疫苗所含B型系别不匹配,在2011-2012、2012-2013、2013-2014、2014-2015、2016-2017年度与疫苗所含B型系别匹配,2018-2019年度与疫苗所含B型系别匹配但抗原性中等程度匹配,交叉反应性低。结论 中国B型流感主要在冬春季流行,强度低于A型流感,不同系病毒的年龄分布存在差异,B型流感流行株与疫苗株多个季节不匹配,需持续开展B型流感的监测和疾病负担评价,完善疫苗免疫策略,提高流感疫苗接种率,降低流感对高危人群的危害。     

Effectiveness of the current and prior influenza vaccinations in Northern Spain, 2018–2019

BackgroundThe population targeted for influenza vaccination can be repeatedly vaccinated over successive seasons, and vaccines received in previous seasons may retain preventive effect. This study aims to estimate the effectiveness of inactivated influenza vaccines received in the current and prior seasons in the 2018–2019 season.MethodsInfluenza-like illness patients attended by sentinel general practitioners or admitted to hospitals in Navarre, Spain, were tested for influenza. Vaccination status in the current and three prior seasons was obtained from the vaccination registry. The test-negative design was used to estimate the vaccine effectiveness.ResultsA total of 381 influenza A(H1N1)pdm09 cases, 341 A(H3N2) cases and 1222 controls were analysed. As compared to individuals unvaccinated in the current and three prior seasons, the influenza vaccine effectiveness against A(H1N1)pdm09 was 57% (95% confidence interval [CI]: 40%, 70%) for current season vaccination regardless of prior doses and 48% (95%CI: 14%, 68%) for vaccination in prior seasons but not in the current season. These estimates were 12% (95%CI: −23%, 37%) and 27% (95%CI: −22%, 56%), respectively, against influenza A(H3N2). Individuals vaccinated with the two A(H1N1)pdm09 strains in influenza vaccines since 2009, A/Michigan/45/2015 and A/California/07/2009, had higher protection (68%; 95%CI: 53%, 77%) than those vaccinated with A/Michigan/45/2015 only (29%, p = 0.020) or with A/California/07/2009 only (34%, p = 0.005).ConclusionThese results suggest moderate effectiveness of influenza vaccination against A(H1N1)pdm09 and low effectiveness against A(H3N2) influenza in the 2018–2019 season. Vaccination in prior seasons maintained a notable protective effect. Strains included in previous vaccines were as effective as the current vaccine strain, and both added their effects against influenza A(H1N1)pdm09.     

Cost-effectiveness of introducing an MF59-adjuvanted trivalent influenza vaccine for older adults in Argentina

IntroductionInfluenza surveillance in Argentina reported influenza-like illness at a rate of 3500/100,000, a hospitalization rate of 15.5/100,000, and a death rate of 0.32/100,000 annually in adults aged over 65 years. The high burden of disease may be due to a combination of immunosenescence and the suboptimal clinical effectiveness of conventional, non-adjuvanted influenza vaccines in this age group. There is a clinical need for more effective influenza vaccines in this population. This study evaluated the cost-effectiveness of an MF59®-adjuvanted trivalent influenza vaccine (aTIV) in adults aged over 65 years in Argentina compared with the non-adjuvanted trivalent influenza vaccine (TIV) used under the current national vaccination policy.MethodsA decision tree cost-effectiveness model was developed to estimate the cost-effectiveness of switching from TIV to aTIV in Argentinian older adults. The model compared cost and health benefits of vaccination in one influenza season from the payer perspective. The main predictions included survival, quality-adjusted survival, and costs. Model inputs were sourced from Argentina or internationally where local data was considered inaccurate. Vaccine efficacy assumptions were extracted from recently published, peer-reviewed scientific literature.ResultsSwitching from TIV to aTIV would result in 170 deaths averted and 1310 incremental quality-adjusted life years (QALYs) gained. The incremental cost-effectiveness ratio per QALY was US $2660.59 from the payer perspective. In all sensitivity analyses, aTIV remained highly cost-effective. The probabilistic sensitivity analyses showed a 95% CI per QALY of US $113.74–7721.67.ConclusionIntroducing an adjuvanted influenza vaccine in Argentina is potentially beneficial and cost-effective relative to the currently-used TIV through the reduction of disease burden and utilization of healthcare resources.     

Factors associated with humoral immune response in older adults who received egg-free influenza vaccine

BackgroundImmune responses to influenza vaccination tend to be lower among older, frequently vaccinated adults. Use of egg-free influenza vaccines is increasing, but limited data exist on factors associated with their immunogenicity in older adults.MethodsCommunity-dwelling older adults ≥ 56 years of age were enrolled in a prospective, observational study of immunogenicity of 2018–2019 influenza vaccine. Hemagglutination inhibition (HAI) antibody titers were measured pre-vaccination (Day 0) and four weeks after vaccination (Day 28) to calculate geometric mean titers, seropositivity (HAI titers ≥ 1:40), seroconversion (fourfold rise in HAI titer with post-vaccination titer ≥ 1:40) and geometric mean fold rise (GMFR). Linear regression models assessed the association of predictors of GMFR for each vaccine antigen.ResultsAmong 91 participants who received egg-free influenza vaccines, 84 (92.3 %) received quadrivalent recombinant influenza vaccine (RIV4, Flublok, Sanofi Pasteur), and 7 (7.7 %) received quadrivalent cell culture-based influenza vaccine (ccIIV4, Flucelvax, Seqirus). Pre-vaccination seropositivity was 52.8 % for A(H1N1), 94.5 % for A(H3N2), 61.5 % for B/Colorado and 48.4 % for B/Phuket. Seroconversion by antigen ranged from 16.5 % for A(H1N1) and B/Colorado to 37.4 % for A(H3N2); 40 participants failed to seroconvert to any antigen. Factors independently associated with higher GMFR in multivariable models included lower pre-vaccination HAI antibody titer for A(H1N1), B/Colorado and B/Phuket, and younger age for A(H1N1).ConclusionOverall pre-vaccination seropositivity was high and just over half of the cohort seroconverted to ≥ 1 vaccine antigen. Antibody responses were highest among participants with lower pre-vaccination titers. Among older adults with high pre-existing antibody titers, approaches to improve immune responses are needed.     

End of season influenza vaccine effectiveness in primary care in adults and children in the United Kingdom in 2018/19

2018/19 was the first season of introduction of a newly licensed adjuvanted influenza vaccine (aTIV) for adults aged 65 years and over and the sixth season in the roll-out of a childhood influenza vaccination programme with a quadrivalent live attenuated influenza vaccine (LAIV). The season saw mainly A(H1N1)pdm09 and latterly A(H3N2) circulation.End-of-season adjusted vaccine effectiveness (aVE) estimates against laboratory confirmed influenza infection in primary care were calculated using the test negative case control method adjusting for key confounders. End-of-season aVE was 44.3% (95% CI: 26.8, 57.7) against all laboratory-confirmed influenza; 45.7% (95% CI: 26.0, 60.1) against influenza A(H1N1)pdm09 and 35.1% (95% CI: −3.7,59.3) against A(H3N2). Overall aVE was 49.9% (95%CI: −13.7, 77.9) for all those ≥ 65 years of age and 62.0% (95% CI: 3.4, 85.0) for those who received aTIV. Overall aVE for 2–17 year olds receiving LAIV was 48.6% (95% CI: −4.4, 74.7). The paper provides evidence of overall significant influenza VE in 2018/19, most notably against influenza A(H1N1)pdm09, however, as seen in 2017/18, there was reduced, non-significant VE against A(H3N2). aTIV provided significant protection for those 65 years of age and over.     

Factors associated with uptake of seasonal and pandemic influenza vaccine among clinical risk groups in the UK: an analysis using the General Practice Research Database

Background

Influenza vaccine uptake rates are low compared with uptake rates of many other vaccines. It is unclear how this differs between risk groups in the population and between pandemic and non-pandemic influenza vaccines.

Aim

This study sought to estimate uptake rates of pandemic and seasonal influenza vaccines among clinical risk groups in the UK during the 2009/2010 influenza season and to identify predictors of vaccine uptake in this cohort.

Methods

Uptake rates were calculated using data from the UK General Practice Research Database (GPRD). Predictors of vaccination were identified using a modified Poisson regression with robust standard error estimates.

Results

Uptake of pandemic influenza vaccine in clinical risk groups was 40.3% and uptake of seasonal influenza vaccine was 61.3%. Factors found to be predictive of seasonal and pandemic influenza vaccination included age and the total number of underlying health conditions an individual had. At risk individuals in those age groups in which universal vaccination of the general population was recommended were more likely to have been vaccinated than individuals in age groups in which only clinical risk groups were recommended for vaccination; hence children in clinical risk groups were more likely to receive pandemic than seasonal influenza vaccine. In older people, having a history of Guillain Barré syndrome was associated with a reduced likelihood of receipt of both seasonal (IRR_adj 0.83, CI₉₅ 0.77–0.90) and pandemic influenza vaccines (IRR_adj 0.82, CI₉₅ 0.73–0.92).

Discussion

Uptake of pandemic influenza vaccine was lower than that of seasonal influenza vaccine among those at a clinically high risk of influenza related morbidity. This suggests that vaccination strategies may need to be altered during future pandemics. Recommending universal vaccination within age categories in which there is a large proportion of high risk individuals could be considered as this may result in higher uptake among clinical risk groups.     

Cost-Effectiveness of Quadrivalent Versus Trivalent Influenza Vaccination in the Dutch National Influenza Prevention Program

ObjectivesAs of 2019, quadrivalent influenza vaccine (QIV) has replaced trivalent influenza vaccine (TIV) in the national immunization program in The Netherlands. Target groups are individuals of 60+ years of age and those with chronic diseases. The objective was to estimate the incremental break-even price of QIV over TIV at a threshold of €20 000 per quality-adjusted life-year (QALY).MethodsAn age-structured compartmental dynamic model was adapted for The Netherlands to assess health outcomes and associated costs of vaccinating all individuals at higher risk for influenza with QIV instead of TIV over the seasons 2010 to 2018. Influenza incidence rates were derived from a global database. Other parameters (probabilities, QALYs and costs) were extracted from the literature and applied according to Dutch guidelines. A threshold of €20 000 per QALY was applied to estimate the incremental break-even prices of QIV versus TIV. Sensitivity analyses were performed to test the robustness of the model outcomes.ResultsRetrospectively, vaccination with QIV instead of TIV could have prevented on average 9500 symptomatic influenza cases, 2130 outpatient visits, 84 hospitalizations, and 38 deaths per year over the seasons 2010 to 2018. This translates into 385 QALYs and 398 life-years potentially gained. On average, totals of €431 527 direct and €2 388 810 indirect costs could have been saved each year.ConclusionUsing QIV over TIV during the influenza seasons 2010 to 2018 would have been cost-effective at an incremental price of maximally €3.81 (95% confidence interval, €3.26-4.31). Sensitivity analysis showed consistent findings on the incremental break-even price in the same range.     

Usage of quadrivalent influenza vaccine among children in the United States, 2013–14

Annual influenza vaccination is recommended for everyone ≥6 months in the U.S. During the 2013–14 influenza season, in addition to trivalent influenza vaccines, quadrivalent vaccines were available, protecting against two influenza A and two influenza B viruses. We analyzed 1,976,443 immunization records from six sentinel sites to compare influenza vaccine usage among children age 6 months–18 years. A total of 983,401 (49.8%) influenza vaccine doses administered were trivalent and 920,333 (46.6%) were quadrivalent (unknown type: 72,709). Quadrivalent vaccine administration varied by age and was least frequent among those <2 years of age.     

Cost-Effectiveness of Routine Childhood Vaccination Against Seasonal Influenza in Germany

ObjectivesIn Germany, routine influenza vaccination with quadrivalent influenza vaccines (QIV) is recommended and reimbursed for individuals ≥60 years of age and individuals with underlying chronic conditions. The present study examines the cost-effectiveness of a possible extension of the recommendation to include strategies of childhood vaccination against seasonal influenza using QIV.MethodsA dynamic transmission model was used to examine the epidemiological impact of different childhood vaccination strategies. The outputs were used in a health economic decision tree to calculate the costs per quality-adjusted life year (QALY) gained from a societal and a third-party payer (TPP) perspective. Strain-specific epidemiology, vaccine uptake, and vaccine efficacy data from the 10 non-pandemic seasons from 2003/2004 to 2013/2014 were used, and cost data were drawn mainly from a health insurance claims data analysis and supplemented by estimates from literature. Uncertainty is explored via scenario, deterministic, and probabilistic sensitivity analyses.ResultsVaccinating 2- to 9-year-olds with QIV assuming a vaccine uptake of 40% is cost-saving with a benefit–cost ratio of 1.66 from a societal perspective and an incremental cost-effectiveness ratio of €998/QALY from a TPP perspective. Lower and higher vaccine uptakes show marginal effects, while extending the target group to 2- to 17-year-olds further increases the health benefits while still being below the willingness-to-pay (WTP) threshold. Assuming no vaccine-induced herd protection has a negative effect on the cost-effectiveness ratio, but childhood vaccination remains cost-effective.ConclusionRoutine childhood vaccination against seasonal influenza in Germany is most likely to be cost-saving from a societal perspective and highly cost-effective from a TPP perspective.     

Active SMS-based influenza vaccine safety surveillance in Australian children

IntroductionAustralia’s novel, active surveillance system, AusVaxSafety, monitors the post-market safety of vaccines in near real time. We analysed cumulative surveillance data for children aged 6 months to 4 years who received seasonal influenza vaccine in 2015 and/or 2016 to determine: adverse event following immunisation (AEFI) rates by vaccine brand, age and concomitant vaccine administration.MethodsParent/carer reports of AEFI occurring within 3 days of their child receiving an influenza vaccine in sentinel immunisation clinics were solicited by Short Message Service (SMS) and/or email-based survey. Retrospective data from 2 years were combined to examine specific AEFI rates, particularly fever and medical attendance as a proxy for serious adverse events (SAE), with and without concomitant vaccine administration. As trivalent influenza vaccines (TIV) were funded in Australia’s National Immunisation Program (NIP) in 2015 and quadrivalent (QIV) in 2016, respectively, we compared their safety profiles.Results7402 children were included. Data were reported weekly through each vaccination season; no safety signals or excess of adverse events were detected. More children who received a concomitant vaccine had fever (7.5% versus 2.8%; p < .001). Meningococcal B vaccine was associated with the highest increase in AEFI rates among children receiving a specified concomitant vaccine: 30.3% reported an AEFI compared with 7.3% who received an influenza vaccine alone (p < .001). Reported fever was strongly associated with medical attendance (OR: 42.6; 95% Confidence Interval (CI): 25.6–71.0). TIV and QIV safety profiles included low and expected AEFI rates (fever: 4.3% for TIV compared with 3.2% for QIV (p = .015); injection site reaction: 1.9% for TIV compared with 3.0% for QIV (p < .001)). There was no difference in safety profile between brands.DiscussionActive participant-reported data provided timely vaccine brand-specific safety information. Our surveillance system has particular utility in monitoring the safety of influenza vaccines, given that they may vary in composition annually.     

Prospective associations of regional social media messages with attitudes and actual vaccination: A big data and survey study of the influenza vaccine in the United States

ObjectiveUsing longitudinal methods to assess regional associations between social media posts about vaccines and attitudes and actual vaccination against influenza in the US.MethodsGeolocated tweets from U.S. counties (N = 115,330) were analyzed using MALLET LDA (Latent Dirichlet allocation) topic modeling techniques to correlate with prospective individual survey data (N = 3005) about vaccine attitudes, actual vaccination, and real-life discussions about vaccines with family and friends during the 2018–2019 influenza season.ResultsTen topics were common across U.S. counties during the 2018–2019 influenza season. In the overall analyses, two of these topics (i.e., Vaccine Science Matters and Big Pharma) were associated with attitudes and behaviors. The topic concerning vaccine science in November-February was positively correlated with attitudes in February-March, r = 0.09, BF₁₀ = 3. Moreover, among respondents who did not discuss the influenza vaccine with family and friends, the topic about vaccine fraud and children in November-February was negatively correlated with attitudes in February-March and with vaccination in February-March, and April-May (rs = −0.18 to −0.25, BF₁₀ = 4–146). However, this was absent when participants had discussions about the influenza vaccine with family and friends.DiscussionRegional vaccine content correlated with prospective measures of vaccine attitudes and actual vaccination.ConclusionsSocial media have demonstrated strong associations with vaccination patterns. When the associations are negative, discussions with family and friends appear to eliminate them. Programs to promote vaccination should encourage real-life conversations about vaccines.     

Reducing Hospital Capacity Needs for Seasonal Respiratory Infections: The Case of Switching to High-Dose Influenza Vaccine for Dutch Older Adults

ObjectivesInfluenza is responsible for considerable health and economic burden every year. Especially older adults are vulnerable for influenza infection and its complications due to immunosenescence and often-underlying medical conditions. Recently, the innovative quadrivalent high-dose influenza vaccine (QIV-HD) has become available in Europe. Through its enhanced immunogenicity, QIV-HD offers improved protection for older adults against respiratory as well as cardiovascular complications. We estimated the potential impact—specifically in terms of hospital admissions and related costs—of a hypothetical past switch from QIV-Standard dose (SD) to QIV-HD in The Netherlands.MethodsEstimates of hospitalizations for the older adults vaccinated with QIV-SD were derived from the seasons 2010/2011-2017/2018. Subsequently, the number of respiratory infections and cardiovascular complications of influenza were estimated for the year 2019/2020 for both QIV-SD and QIV-HD. To calculate the overall corresponding savings, costs for hospital complications, derived from literature, were used.ResultsWhen QIV-HD would have been used instead of QIV-SD during the season 2019/2020, an additional 220 hospitalizations would have been averted among older adults of 60 years and older in the Netherlands. This corresponds to savings of €1 219 779 (uncertainty interval: 1 089 813-1 348 549), of which 69% is attributable to cardiovascular-related hospitalizations.ConclusionsWe demonstrate that a relevant improvement in influenza vaccination among older adults in The Netherlands can be achieved by switching from the current QIV-SD to QIV-HD. Not only comes a switch from QIV-SD to QIV-HD with a significant reduction in pressure on hospital capacity but also with notable cost savings.     

A real-world study evaluating the relative vaccine effectiveness of a cell-based quadrivalent influenza vaccine compared to egg-based quadrivalent influenza vaccine in the US during the 2017–18 influenza season

BackgroundCell-based influenza vaccine manufacturing reduces egg adaptations that can decrease vaccine effectiveness. We evaluated the relative vaccine effectiveness (rVE) of cell-based quadrivalent influenza vaccine (QIVc) compared to standard-dose egg-based quadrivalent influenza vaccines (QIVe-SD) against influenza-related and serious respiratory events among subjects 4–64 years of age during the 2017–18 influenza season.MethodsA retrospective cohort analysis was conducted using administrative claims data in the US (IQVIA PharMetrics Plus® database). Subjects vaccinated with QIVc or QIVe-SD from 8/2017–1/2018 were identified (date of vaccination termed the index date). Influenza-related hospitalizations/ER visits, all-cause hospitalizations and serious respiratory hospitalizations/ER visits were assessed post-vaccination. Inverse probability of treatment weighting (IPTW) and Poisson regression were used to evaluate the adjusted rVE of QIVc compared to QIVe-SD. In a subgroup analysis, rVE was assessed for several subgroups of interest (4–17, 18–64 and 50–64 years, and subjects with ≥1 high-risk condition). In a secondary economic analysis, annualized all-cause costs over the follow-up were compared using propensity score matching (PSM) and generalized estimating equation (GEE) models.ResultsThe study sample comprised 555,538 QIVc recipients and 2,528,524 QIVe-SD recipients. Prior to adjustment, QIVc subjects were older and had higher total costs in the 6-months pre-index. Following IPTW-adjustment and Poisson regression, QIVc was more effective in reducing influenza-related hospitalizations/ER visits, all-cause hospitalizations, and hospitalizations/ER visits related to asthma/COPD/bronchial events and other respiratory events compared to QIVe-SD. Similar trends were generally observed in the subgroup analysis. Following PSM adjustment and GEE regression, QIVe-SD was associated with significantly higher annualized all-cause total costs compared to QIVc, driven by higher costs for outpatient medical services and inpatient hospitalizations.ConclusionsAfter adjustment for confounders and selection bias, QIVc reduced influenza-related hospitalizations/ER visits, all-cause hospitalizations, and serious respiratory hospitalizations/ER visits compared to QIVe-SD. QIVc was associated with significantly lower all-cause total costs.     

Receipt of COVID-19 and seasonal influenza vaccines in California (USA) during the 2021–2022 influenza season

BackgroundDespite lower circulation of influenza virus throughout 2020–2022 during the COVID-19 pandemic, seasonal influenza vaccination has remained a primary tool to reduce influenza-associated illness and death. The relationship between the decision to receive a COVID-19 vaccine and/or an influenza vaccine is not well understood.MethodsWe assessed predictors of receipt of 2021–2022 influenza vaccine in a secondary analysis of data from a case-control study enrolling individuals who received SARS-CoV-2 testing. We used mixed effects logistic regression to estimate factors associated with receipt of seasonal influenza vaccine. We also constructed multinomial adjusted marginal probability models of being vaccinated for COVID-19 only, seasonal influenza only, or both as compared with receipt of neither vaccination.ResultsAmong 1261 eligible participants recruited between 22 October 2021–22 June 2022, 43% (545) were vaccinated with both seasonal influenza vaccine and >1 dose of a COVID-19 vaccine, 34% (426) received >1 dose of a COVID-19 vaccine only, 4% (49) received seasonal influenza vaccine only, and 19% (241) received neither vaccine. Receipt of >1 COVID-19 vaccine dose was associated with seasonal influenza vaccination (adjusted odds ratio [aOR]: 3.72; 95% confidence interval [CI]: 2.15–6.43); this association was stronger among participants receiving >1 COVID-19 booster dose (aOR = 16.50 [10.10–26.97]). Compared with participants testing negative for SARS- CoV-2 infection, participants testing positive had lower odds of receipt of 2021-2022 seasonal influenza vaccine (aOR = 0.64 [0.50–0.82]).ConclusionsRecipients of a COVID-19 vaccine were more likely to receive seasonal influenza vaccine during the 2021–2022 season. Factors associated with individuals’ likelihood of receiving COVID-19 and seasonal influenza vaccines will be important to account for in future studies of vaccine effectiveness against both conditions. Participants who tested positive for SARS-CoV-2 in our sample were less likely to have received seasonal influenza vaccine, suggesting an opportunity to offer influenza vaccination before or after a COVID-19 diagnosis.     

Safety of recombinant quadrivalent influenza vaccine compared to inactivated influenza vaccine in Chinese adults: An observational study

BackgroundRecombinant influenza vaccine (RIV) has been in use in US adults since 2013. This study evaluated the safety of quadrivalent recombinant influenza vaccine (RIV4, Flublok® Quadrivalent, Sanofi Pasteur) compared with standard-dose quadrivalent inactivated influenza vaccine (SD-IIV4) in self-identified Chinese adults at Kaiser Permanente Northern California (KPNC).MethodsThis study evaluated adults aged 18–64 years within KPNC during the 2018–2019 influenza season who self-identified as Chinese (NCT03694392). We compared the rates of prespecified diagnoses of interest in the emergency department and inpatient settings as done in prior influenza studies, for three risk intervals: 0–2 days, 0–13 days, and 0–41 days following influenza vaccination, as well as number of deaths within 0–180 days after vaccination. We estimated the odds ratios (ORs) and 95% confidence intervals using logistic regression adjusted for sex, age group, presence of comorbidities, and same-day concomitant vaccination.ResultsComparing 15,574 adults who received RIV4 with 27,110 who received SD-IIV4, there was no statistically significant difference in the prespecified diagnoses of interest and deaths between the 2 groups. There were 35 deaths total, none of which were considered to be related to influenza vaccination.ConclusionsThis study did not identify any safety concerns regarding RIV4 use among 18–64-year-olds who self-identified as Chinese. This study supports the safety of RIV4 vaccine in this population.