Quadrivalent Inactivated Vaccine Research Articles

Immunogenicity and safety of inactivated quadrivalent influenza vaccine compared with the trivalent vaccine for influenza infection: an overview of systematic reviews

BackgroundInfluenza infection is a highly preventable transmissible viral disease associated with mild upper respiratory symptoms and more severe conditions such as lethal pneumonia. Studies have shown that a broader spectrum influenza vaccine could reduce influenza’s burden of disease in low- and middle-income countries. A considerable number of systematic reviews reported that quadrivalent influenza vaccines are considered more effective compared to trivalent vaccines, hence, there is a need for an overview in order to synthesize the current evidence pertaining to the comparison between quadrivalent and trivalent inactivated influenza vaccines. Objective: The aim was to summarize the evidence from systematic reviews that investigated the immunogenicity and safety of the Influenza’s inactivated quadrivalent vaccine (QIV) compared to the trivalent vaccine (TIV), in the general population.MethodsWe searched articles up to December 2022 at: Web of Science, EMBASE, MEDLINE, Cochrane Library, and SCOPUS. The search strategy was conducted following the PICO model. We included systematic reviews comparing the primary outcomes of immunogenicity (seroprotection rate and seroconversion rate) and adverse events using risk ratios. The AMSTAR 2 and ROBIS were used for quality assessments, and GRADE was used for evidence certainty assessments.FindingsWe included five systematic reviews, totalling 47,740 participants. The Quadrivalent Inactivated Influenza Vaccine (QIV) exhibited enhanced immunogenicity in the context of B-lineage mismatch when compared to the Trivalent Inactivated Influenza Vaccine (TIV). While the safety profile of QIV was found to be comparable to that of TIV, the QIV showed a higher incidence of solicited local pain among children and adolescents, as well as an increased frequency of local adverse events within the adult population.ConclusionOur findings suggest that the QIV provides a superior immunogenicity response compared to the TIV in all age groups evaluated, especially when a lineage mismatch occurred. The safety of QIV was considered similar to the TIV, with no serious or systemic solicited or unsolicited adverse events; tough pain at the injection site was greater for QIV. We recommend caution owing to the high risk of bias in the selection process and no protocol registration.

Cost-Effectiveness and Health Impacts of Different Influenza Vaccination Strategies for Children in China

Authors aimed to evaluate the economic and health impacts of three influenza vaccines available in China, including trivalent inactivated vaccine, quadrivalent inactivated vaccine, and live attenuated influenza vaccine, for children aged six months to 18 years. Two decision-analytic models were developed to simulate four vaccination strategies. Outcomes included total costs from a societal perspective in 2021, quality-adjusted life-year loss, numbers of outpatient and inpatient cases, and deaths avoided using each strategy. Deterministic and probabilistic sensitivity analyses were performed to examine the uncertainty of model inputs. For children aged six months to three years, trivalent inactivated vaccine saved $48 million and avoided a loss of 17,637 quality-adjusted life-years compared with no vaccination. For children aged 3-18 years, quadrivalent inactivated vaccine was cost-effective compared with trivalent inactivated vaccine, with an incremental cost-effectiveness ratio of $32,948.5/quality-adjusted life-year (willingness-to-pay threshold=$37,653/quality-adjusted life-year), which was sensitive to the RR of vaccine effectiveness of quadrivalent inactivated vaccine versus of trivalent inactivated vaccine. When compared with quadrivalent inactivated vaccine, live attenuated influenza vaccine was $1.28 billion more costly but gained an additional 13,560 quality-adjusted life-years; its incremental cost-effectiveness ratio was $123,983.8/quality-adjusted life-year. Live attenuated influenza vaccine would be cost-effective if its vaccine effectiveness was >0.79. Probabilistic sensitivity analysis revealed that quadrivalent inactivated vaccine, trivalent inactivated vaccine, live attenuated influenza vaccine, and no vaccination were cost-effective in 55.94%, 33.09%, 10.97%, and 0% of 10,000 Monte Carlo simulations. Trivalent inactivated vaccine was cost-effective compared with no vaccination in children aged six months to 18 years. Of the three vaccination strategies for children aged 3-18 months, quadrivalent inactivated vaccine appears to be the most cost-effective.

Cost Effectiveness of Quadrivalent Versus Trivalent Inactivated Influenza Vaccines for the Portuguese Elderly Population.

Background: quadrivalent inactivated vaccine (QIV) has replaced trivalent inactivated vaccine (TIV). In Portugal, TIV is free of charge for risk groups, including older adults (≥65 years old). In its turn, QIV—which provides broader protection as it includes an additional lineage B strain—was introduced in Portugal in October 2018; only since the 2019/20 influenza season has it been provided free of charge for risk groups. This study evaluates the cost effectiveness of switching from TIV to QIV, from the National Health Service perspective, in the Portuguese elderly mainland population. Methods: A decision tree model was developed to compare TIV and QIV, based on Portuguese hospitalization data for the 2015/16 influenza season. The primary health economic outcome under consideration was the incremental cost-effectiveness ratio (ICER). In addition, one-way sensitivity analysis and probabilistic sensitivity analysis were performed. Results: the high cost of QIV (approximately three times the cost of TIV) would lead to a total increment of EUR 5,283,047, and the resulting ICER would be EUR 26,403,007/QALY, above the usual willingness-to-pay threshold. Conclusions: from the National Health Service perspective, our findings reveal that QIV is not cost effective for the Portuguese elderly population due to the high cost. If the QIV costs were the same as the TIV, then QIV would be cost effective.

Safety and immunogenicity of a quadrivalent influenza vaccine in adults aged 60 years or above: a phase III randomized controlled clinical study

ABSTRACT To control seasonal influenza epidemics in elders, a quadrivalent, inactivated, split-virion influenza vaccine (IIV4) comprising A and B lineages is produced for young individuals and adults aged ≥60 years. In this phase III, randomized, double-blind, active-controlled trial, we compared safety and immunogenicity of IIV4 with a licensed quadrivalent inactivated vaccine (IIV4-HL) produced by Hualan Biological Engineering during the 2019 influenza season. Participants were randomly assigned to receive IIV4 (n = 959) or IIV4-HL (n = 959). Compared to IIV4-HL, geometric mean titers (GMT) of hemagglutination inhibition (HAI) titers and seroconversion rate (SCR) of IIV4 demonstrated better antibody responses in A lineages (H1N1 and H3N2) (P < .01) and equivalent antibody responses in B lineages (B/Yamagata and B/Victoria) (P > .01) in both age groups. After immunization, IIV4 provided a satisfactory SCR and seroprotection rate (SPR) in elders. No discernible variation in immunogenicity was observed between the two age cohorts. In both age groups, IIV4 and IIV4-HL recipients experienced similar levels of solicited and unsolicited adverse events (AEs), and the incidence of AEs was low in both vaccine groups. Most AEs were of mild-to-moderate severity and no grade 3 AEs in IIV4 group, but AEs in adults aged 60–65 were little higher than in adults over 65 years in IIV4 and IIV4-HL groups (IIV4: 14.66% vs. 10.36%; IIV4-HL:14.67% vs. 11.43%). Totally, IIV4 was generally well tolerated and induced high antibody titers against all four influenza strains in elderly, making it a compelling alternative for the elderly aged ≥60 years. Trial registration: Clinical Trials.gov: 2015L00649-2.

Animal Models Utilized for the Development of Influenza Virus Vaccines.

Animal models have been an important tool for the development of influenza virus vaccines since the 1940s. Over the past 80 years, influenza virus vaccines have evolved into more complex formulations, including trivalent and quadrivalent inactivated vaccines, live-attenuated vaccines, and subunit vaccines. However, annual effectiveness data shows that current vaccines have varying levels of protection that range between 40–60% and must be reformulated every few years to combat antigenic drift. To address these issues, novel influenza virus vaccines are currently in development. These vaccines rely heavily on animal models to determine efficacy and immunogenicity. In this review, we describe seasonal and novel influenza virus vaccines and highlight important animal models used to develop them.

Influenza vaccination: protecting the most vulnerable.

Influenza virus infection causes seasonal epidemics and occasional pandemics, leading to huge morbidity and mortality worldwide. Vaccination against influenza is needed annually as protection from constantly mutating strains is required. Groups at high risk of poor outcomes include the elderly, the very young, pregnant women and those with chronic health conditions. However, vaccine effectiveness in the elderly is generally poor due to immunosenescence and may be altered due to "original antigenic sin". Strategies to overcome these challenges in the elderly include high-dose or adjuvant vaccines. Other options include vaccinating healthcare workers and children as this reduces community-level influenza transmission. Current guidelines in the UK are that young children receive a live attenuated nasal spray vaccine, adults aged >65 years receive an adjuvanted trivalent inactivated vaccine and adults aged <65 years with comorbidities receive a quadrivalent inactivated vaccine. The goal of a universal influenza vaccine targeting conserved regions of the virus and avoiding the need for annual vaccination is edging closer with early-phase trials under way.

Cost-Effectiveness of Pediatric Influenza Vaccination in The Netherlands

ObjectiveThis study evaluates the cost-effectiveness of extending the Dutch influenza vaccination program for elderly and medical high-risk groups to include pediatric influenza vaccination, taking indirect protection into account. MethodsAn age-structured dynamic transmission model was used that was calibrated to influenza-associated GP visits over 4 seasons (2010-2011 to 2013-2014). The clinical and economic impact of different pediatric vaccination strategies were compared over 20 years, varying the targeted age range, the vaccine type for children or elderly and high-risk groups. Outcome measures include averted symptomatic infections and deaths, societal costs and quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Costs and QALYs were discounted at 4% and 1.5% annually. ResultsAt an assumed coverage of 50%, adding pediatric vaccination for 2- to 17-year-olds with quadrivalent live-attenuated vaccine to the current vaccination program for elderly and medical high-groups with quadrivalent inactivated vaccine was estimated to avert, on average, 401 820 symptomatic cases and 72 deaths per year. Approximately half of averted symptomatic cases and 99% of averted deaths were prevented in other age groups than 2- to 17-year-olds due to herd immunity. The cumulative discounted 20-year economic impact was 35 068 QALYs gained and €1687 million saved, that is, the intervention was cost-saving. This vaccination strategy had the highest probability of being the most cost-effective strategy considered, dominating pediatric strategies targeting 2- to 6-year-olds or 2- to 12-year-olds or strategies with trivalent inactivated vaccine. ConclusionModeling indicates that introducing pediatric influenza vaccination in The Netherlands is cost-saving, reducing the influenza-related disease burden substantially.

Efficacy, immunogenicity, and safety of a plant-derived, quadrivalent, virus-like particle influenza vaccine in adults (18–64 years) and older adults (≥65 years): two multicentre, randomised phase 3 trials

Seasonal influenza remains a substantial public health threat despite the availability of egg-derived and other vaccines. Plant-based manufacturing might address some of the limitations of current vaccines. We describe two phase 3 efficacy studies of a recombinant quadrivalent virus-like particle (QVLP) influenza vaccine manufactured in plants, one in adults aged 18-64 years (the 18-64 study) and one in older people aged 65 years and older (the 65-plus study). We did two randomised, observer-blind, multinational studies in the northern hemisphere in the 2017-18 (the 18-64 study) and 2018-19 (the 65-plus study) influenza seasons. The 18-64 study was done at 73 sites and the 65-plus study was done at 104 sites, both across Asia, Europe, and North America. In the 18-64 study, inclusion criteria were body-mass index less than 40 kg/m2; age 18-64 years at screening visit; and good health. In the 65-plus study, inclusion criteria were body-mass index of maximum 35 kg/m2; aged 65 years or older at screening visit; not living in a rehabilitation centre or care home; and no acute or evolving medical problems. Participants in the 18-64 study were randomly assigned (1:1) to receive either QVLP vaccine (30 μg haemagglutinin per strain) or placebo. Participants in the 65-plus study were randomly assigned (1:1) to receive QVLP vaccine (30 μg haemagglutinin per strain) or quadrivalent inactivated vaccine (QIV; 15 μg haemagglutinin per strain). The primary outcome in the 18-64 study was absolute vaccine efficacy to prevent laboratory-confirmed, respiratory illness caused by antigenically matched influenza strains. The primary outcome in the 65-plus study was relative vaccine efficacy to prevent laboratory-confirmed influenza-like illness caused by any influenza strain. The primary analyses were done in the per-protocol population and safety was assessed in all participants who received the assigned treatment. These studies are registered with ClinicalTrials.gov (18-64 study NCT03301051; 65-plus study NCT03739112). In the 18-64 study, between Aug 30, 2017, and Jan 15, 2018, 10 160 participants were randomly assigned to receive either QVLP vaccine (5077 participants) or placebo (5083 participants). The per-protocol population consisted of 4814 participants in the QVLP group and 4812 in the placebo group. The study did not meet its primary endpoint of 70% absolute vaccine efficacy for the QVLP vaccine (35·1% [95% CI 17·9 to 48·7]) against respiratory illness caused by matched strains. 55 (1·1%) of 5064 participants in the QVLP group versus 51 (1·0%) of 5072 in the placebo group had a serious adverse event. Four (0·1%) and six [0·1%] participants had severe treatment-related treatment-emergent adverse events. In the 65-plus study, between Sept 18, 2018, and Feb 22, 2019, 12 794 participants were randomly assigned to receive either QVLP vaccine (6396 participants) or QIV (6398 participants). The per-protocol population consisted of 5996 participants in the QVLP group and 6026 in the QIV group. The study met its primary non-inferiority endpoint with a relative vaccine efficacy of the QVLP vaccine for the prevention of influenza-like illness caused by any strain of 8·8% (-16·7 to 28·7). 263 (4·1%) of 6352 participants in the QVLP group versus 266 (4·2%) of 6366 in the QIV group had serious adverse events (one [<0·1%] vs two [<0·1%] were considered treatment-related); one (<0·1%) versus three (<0·1%) participants had severe treatment-related treatment-emergent adverse events. These efficacy studies are the first large-scale studies of any plant-derived human vaccine. Together, they show that the plant-derived QVLP vaccine can provide substantial protection against respiratory illness and influenza-like illness caused by influenza viruses in adults. QVLP vaccine was well tolerated and no major safety signal arose in participants who received QVLP vaccine across the two studies. Medicago.

Effectiveness of Trivalent and Quadrivalent Inactivated Vaccines Against Influenza B in the United States, 2011-2012 to 2016-2017.

BackgroundSince 2013, quadrivalent influenza vaccines containing 2 B viruses gradually replaced trivalent vaccines in the United States. We compared the vaccine effectiveness of quadrivalent to trivalent inactivated vaccines (IIV4 to IIV3, respectively) against illness due to influenza B during the transition, when IIV4 use increased rapidly.MethodsThe US Influenza Vaccine Effectiveness (Flu VE) Network analyzed 25 019 of 42 600 outpatients aged ≥6 months who enrolled within 7 days of illness onset during 6 seasons from 2011–2012. Upper respiratory specimens were tested for the influenza virus type and B lineage. Using logistic regression, we estimated IIV4 or IIV3 effectiveness by comparing the odds of an influenza B infection overall and the odds of B lineage among vaccinated versus unvaccinated participants. Over 4 seasons from 2013–2014, we compared the relative odds of an influenza B infection among IIV4 versus IIV3 recipients.ResultsTrivalent vaccines included the predominantly circulating B lineage in 4 of 6 seasons. During 4 influenza seasons when both IIV4 and IIV3 were widely used, the overall effectiveness against any influenza B was 53% (95% confidence interval [CI], 45–59) for IIV4 versus 45% (95% CI, 34–54) for IIV3. IIV4 was more effective than IIV3 against the B lineage not included in IIV3, but comparative effectiveness against illnesses related to any influenza B favored neither vaccine valency.ConclusionsThe uptake of quadrivalent inactivated influenza vaccines was not associated with increased protection against any influenza B illness, despite the higher effectiveness of quadrivalent vaccines against the added B virus lineage. Public health impact and cost-benefit analyses are needed globally.

2759. Immunogenicity of Inactivated Influenza Vaccines Given Early vs. Late After Pediatric Allogeneic Hematopoietic Cell Transplantation

BackgroundPediatric hematopoietic cell transplant (HCT) recipients often fail to have robust responses to influenza (flu) vaccine. We conducted a blinded phase II trial comparing high-dose (HD) trivalent inactivated vaccine (TIV) vs. standard dose (SD) quadrivalent inactivated vaccine (QIV).MethodsChildren 3–17 years old and 3–35 months post-allogeneic HCT were enrolled at 9 centers and randomized to either 2 doses of HD-TIV or SD-QIV during the 2016–2017 flu season. We compared immune responses by hemagglutination inhibition (HAI) from children 3–11 (early) vs. 12–35 (late) months (m) post-HCT to 3 common flu vaccine antigens, irrespective of vaccine type. HAI responses were evaluated at baseline (visit 1), 1 m post dose 1 (visit 2) and dose 2 (visit 3), and 7 m post dose 2 (visit 4). Geometric mean titers (GMT) were adjusted for baseline log-titer values.ResultsThirty-one children, median age 11 (7–15) years, were enrolled; 17 (55%) were immunized early and 14 (45%) late. Over 50% of patients had a potentially seroprotective (≥1:40) HAI titer at baseline, with no significant difference post-vaccination between early and late subjects. Table 1 compares early vs late subjects with HAI seroconversion (4-fold HAI titer rise). Post dose 1, late subjects, compared with early, had higher rates of seroconversion to all influenza strains. Post dose 2, early subjects, compared with late, had increased seroconversion. Late subjects had higher GMTs for H1N1 post dose 1 and 2, H3N2 after dose 1, and strain B/VIC post dose 1 and 2 (Figure 1). Although immunogenicity waned throughout flu season, higher seroconversion rates and GMT to H3N2 and strain B/VIC were retained in late subjects.ConclusionCompared with subjects in early post-HCT group, late post-HCT subjects had better flu vaccine immune responses as noted by higher GMT and HAI seroconversion. However, 2 doses seemed more beneficial in the early post-HCT group. Future analyses are underway, including comparing immunogenicity of HD vs. SD flu vaccine. DisclosuresJennifer E. Schuster, MD, Satchel Health: Shareholder Flor M. Munoz, M.D, Biocryst: Grant/Research Support; CDC: Research Grant; Moderna: Other Financial or Material Support, Safety Monitoring Board Member/Chair; NIH: Research Grant; Novavax: Research Grant; UP to Date: Author and Editor - Royalties, Other Financial or Material Support.

High performance of rapid influenza diagnostic test and variable effectiveness of influenza vaccines in Mexico

ObjectivesTo evaluate the performance of rapid influenza diagnostic tests (RIDT) and influenza vaccines’ effectiveness (VE) during an outbreak setting. MethodsWe compared the performance of a RIDT with RT-PCR for influenza virus detection in influenza-like illness (ILI) patients enrolled during the 2016/17 season in Mexico City. Using the test-negative design, we estimated influenza VE in all participants and stratified by age, virus subtype, and vaccine type (trivalent vs quadrivalent inactivated vaccines). The protective value of some clinical variables was evaluated by regression analyses. ResultsWe enrolled 592 patients. RT-PCR detected 93 cases of influenza A(H1N1)pdm09, 55 of AH3N2, 141 of B, and 13 A/B virus infections. RIDT showed 90.7% sensitivity and 95.7% specificity for influenza A virus detection, and 91.5% sensitivity and 95.3% specificity for influenza B virus detection. Overall VE was 33.2% (95% CI: 3.0–54.0; p = 0.02) against any laboratory-confirmed influenza infection. VE estimates against influenza B were higher for the quadrivalent vaccine. Immunization and occupational exposure were protective factors against influenza. ConclusionsThe RIDT was useful to detect influenza cases during an outbreak setting. Effectiveness of 2016/17 influenza vaccines administered in Mexico was low but significant. Our data should be considered for future local epidemiological policies.

Adjuvanted influenza vaccine for the Italian elderly in the 2018/19 season: an updated health technology assessment.

BackgroundThe elderly, defined here as subjects aged ≥ 65 years, are among at-risk subjects for whom annual influenza vaccination is recommended. For the 2018/19 season, three vaccine types are available for the elderly in Italy: trivalent inactivated vaccine (TIV), adjuvanted TIV (aTIV) and quadrivalent inactivated vaccines (QIV). No health technology assessment (HTA) of seasonal influenza vaccination in the elderly has previously been conducted in Italy.MethodsAn HTA was conducted in 2017 to analyze the burden of influenza illness, the characteristics, efficacy, safety and cost-effectiveness of available vaccines and the related organizational and ethical implications. This was then contextualized to the 2018/19 influenza season. Comprehensive literature reviews/analyses were performed and a static mathematical model developed in order to address the above issues.ResultsIn Italy, influenza is usually less common in the elderly than in other age-classes, but the burden of disease is the highest; >10% of infected elderly subjects develop complications, and about 90% of all influenza-related deaths occur in this age-class. All available vaccines are effective, safe and acceptable from an ethical standpoint. However, aTIV has proved more immunogenic and effective in the elderly. Furthermore, from the third payer’s perspective, aTIV is highly cost-effective and cost-saving in comparison with TIV and QIV, respectively. Nevertheless, vaccination coverage needs to be improved.ConclusionsAccording to this HTA, aTIV appeared the vaccine of choice in the elderly. HTA should be reapplied whenever new relevant data become available.

Effectiveness of the quadrivalent inactivated influenza vaccine in Japan during the 2015–2016 season: A test-negative case-control study comparing the results by real time PCR, virus isolation

BackgroundWe estimated influenza vaccine effectiveness (VE) in 2015–2016 season against medically attended, laboratory-confirmed influenza, when quadrivalent inactivated vaccine (IIV4) was first introduced in Japan, using test-negative case-control design. Influenza A(H1N1)pdm09 cocirculated with B/Yamagata and B/Victoria during the study period in Japan. MethodWe based our case definition on two laboratory tests, real-time reverse transcription polymerase chain reaction (RT PCR), and virus isolation and compared VEs based on these tests. In addition, VE was evaluated by rapid diagnostic test (RDT). Nasopharyngeal swabs were collected from outpatients who visited clinics with influenza-like illness (ILIs) in Hokkaido, Niigata, Gunma and Nagasaki prefectures. ResultsAmong 713 children and adults enrolled in this study, 578 were influenza positive by RT PCR including, 392 influenza A and 186 influenza B, while 135 were tested negative controls. The adjusted VE by RT PCR for all ages against any influenza was low protection of 36.0% (95% confidence interval [CI], 3.1% to 58.6%), for influenza A was 30.0% (95% CI: −10.0% to 55.5%), and influenza B was moderate 50.2% (95% CI: 13.3% to 71.4%). Adjusted VE for virus isolation for A(H1N1)pdm09 was 37.1% (95% CI: 1.7% to 59.7%), Yamagata lineage 51.3% (95% CI: 6.4% to 74.7%) and Victoria lineage 21.3% (95% CI: −50.0% to 58.9%). VE was highest and protective in 0–5 years old group against any influenza and influenza A and B/Yamagata, but the protective effect was not observed for other age groups and B/Victoria. RDT demonstrated concordant results with RT PCR and virus isolation. Sequencing of hemagglutinin gene showed that all A(H1N1)pdm09 belong to clade 6B including 31 strains (88.6%), which belong to clade 6B.1 possessing S162N mutations that may alter antigenicity and affect VE for A(H1N1)pdm09. ConclusionsIIV4 influenza vaccine during 2015–2016 was effective against A(H1N1)pdm09 and the two lineages of type B. Younger children was more protected than older children and adults by vaccination.

Vaccin grippal quadrivalent : quels changements pour quels bénéfices ?

Currently, circulating viruses responsible for annual seasonal influenza epidemics belong to two influenza A subtypes, A(H1N1) and A(H3N2), and to two antigenically distinct type B lineages, B/Yamagata and B/Victoria lineages. Like diseases due to influenza A virus, influenza B virus diseases may have severe consequences and should be prevented. Until now, in France, the vaccines used to prevent seasonal influenza were trivalent, systematically targeting viruses belonging to both A subtypes and to one or other of the B lineages. The protective efficacy of trivalent vaccines is diminished during the seasons when viruses belonging to both B lineages cocirculated or when the circulating dominant type B virus belonged to a lineage different from that targeted by the vaccine strain. By targeting viruses belonging to both B lineages, quadrivalent vaccines improve the antigenic concordance between circulating and vaccine type B strains. Three inactivated quadrivalent vaccines are authorized for marketing in France and should be available for the 2018-2019 season. It is expected that, by providing enlarged protection, these quadrivalent influenza vaccines will improve vaccine efficacy, the confidence in immunization of the public, the satisfaction of health professionals, and ultimately will help to complete immunization coverage.

Cost-effectiveness analysis of different seasonal influenza vaccines in the elderly Italian population

ABSRACTIn the perspective of reaching at least 75% influenza vaccination coverage in the elderly and substantial budget constraints, Italian decision makers are facing important challenges in determining an optimal immunization strategy for this growing and particularly vulnerable population. Four different influenza vaccines are currently available for Italian older adults aged 65 years or above, namely trivalent inactivated vaccines (TIVs), MF59-adjuvanted TIV (MF59-TIV), intradermal TIV (ID-TIV) and quadrivalent inactivated vaccines (QIVs). The present study is the first to compare the cost-effectiveness profiles of virtually all possible public health strategies, including the aforementioned four vaccine formulations as well non-vaccination. For this purpose, a decision tree model was built ex novo; the analysis was conducted from the third-payer perspective in the timeframe of one year. All available vaccines were cost-effective compared with non-vaccination. However, MF59-TIV had the most favorable economic profile in the Italian elderly population. Indeed, compared with non-vaccination, it was deemed highly cost-effective with an incremental cost-effectiveness ratio (ICER) of €10,750 per quality-adjusted life year (QALY). The ICER was much lower (€4,527/QALY) when MF59-TIV was directly compared with TIV. ID-TIV and QIV were dominated by MF59-TIV as the former comparators were associated with greater total costs and lower health benefits. Both deterministic and probabilistic sensitivity analyses confirmed robustness of the base case results. From the economic perspective, MF59-TIV should be considered as a preferential choice for Italian older adults aged 65 years or above.

Translation of the UK Pediatric Influenza Vaccination Programme in Primary Schools to 13 European Countries Using a Dynamic Transmission Model.

Objectives: To simulate the impact of a pediatric influenza vaccination programme using quadrivalent live attenuated influenza vaccine (QLAIV) in Europe by applying coverage rates achieved in the United Kingdom during the 2014-2015 season and to compare the model outcomes to the UK results. Methods: We used a deterministic, age-structured, dynamic transmission model adapted to the demography, contact patterns and influenza incidence of 13 European countries, with a 10-year horizon. The reference strategy was the unchanged country-specific coverage rate, using quadrivalent inactivated vaccine (assumed efficacy against infection from 45% in 1-year-old children to 60% in healthy adults). In the evaluated strategy, 56.8% of 5-10-year-old children were additionally vaccinated with QLAIV (assumed efficacy 80%), as was the case in 2014-2015 in the United Kingdom's primary school pilot areas. Symptomatic influenza cases and associated medical resources (primary care consultations [PCC], hospitalization, intensive care unit [ICU] admissions) were calculated. The evaluated versus reference strategies were compared using odds ratios (ORs) for PCC in the target (aged 5-10-years) and non-target adult (aged >17 years) populations as well as number needed to vaccinate (NNV) with QLAIV to avert one PCC, hospitalization or ICU admission. Model outcomes, averaged over 10 seasons, were compared with published real-life data from the United Kingdom for the 2014-2015 season. Results: Over 13 countries and 10 years, the evaluated strategy prevented 32.8 million of symptomatic influenza cases (172.3 vs 205.2 million). The resulting range of ORs for PCC was 0.18-0.48 among children aged 5-10-years, and the published OR in the United Kingdom was 0.06 (95% confidence interval [0.01; 0.62]). In adults, the range of ORs for PCC was 0.60-0.91 (UK OR=0.41 [0.19; 0.86]). NNV ranges were 6-19 per averted PCC (UK NNV=16), 530-1524 per averted hospitalization (UK NNV=317) and 5298-15 241 per averted ICU admission (UK NNV=2205). Conclusions: Across a range of European countries, our model shows the beneficial direct and indirect impact of a paediatric vaccination programme using QLAIV in primary school-aged children, consistent with what was observed during a single season in the United Kingdom. Recommendations for the implementation of pediatric vaccination programmes are, therefore, supported in Europe.

Direct and Indirect Protection with Pediatric Quadrivalent Live-Attenuated Influenza Vaccination in Europe Estimated by a Dynamic Transmission Model.

Objectives: To estimate the public health impact of annual vaccination of children with a quadrivalent live-attenuated influenza vaccine (QLAIV) across Europe. Methods: A deterministic, age-structured, dynamic model was used to simulate influenza transmission across 14 European countries, comparing current vaccination coverage using a quadrivalent inactivated vaccine (QIV) to a scenario whereby vaccination coverage was extended to 50% of 2-17 year-old children, using QLAIV. Differential equations described demographic changes, exposure to infectious individuals, recovery and immunity dynamics. For each country, the basic reproduction number (R0) was calibrated to published influenza incidence statistics. Assumed vaccine efficacy for children was 80% (QLAIV) and 59% (QIV). Symptomatic cases cumulated over 10 years were calculated per 100 000 person-years. One-way sensitivity analyses were conducted on QLAIV efficacy in 7-17 year-olds (59% instead of 80%), durations of natural (±3 years; base case: 6, 12 years for influenza A, B respectively) and QLAIV vaccine-induced immunity (100% immunity loss after 1 season; base case: 30%), and R0 (+/-10% around all-year average value). Results: Across countries, annual QLAIV vaccination additionally prevents 1366-3604 symptomatic cases per 100 000 population (average 2495 /100 000, ie, a reduction of 47.6% of the cases which occur in the reference scenario with QIV vaccination only). Among children (2-17 years), QLAIV prevents 551-1555 cases per 100 000 population (average 990 /100 000, ie, 67.2% of current cases). Among adults, QLAIV indirectly prevents 726-2047 cases per 100 000 population (average 1466 /100 000, ie, 40.0% of current cases). The most impactful drivers of total protection were duration of natural immunity against influenza A, R0 and QLAIV immunity duration and efficacy. In all evaluated scenarios, there was a large direct and even larger indirect protection compared with the reference scenario. Conclusions: The model highlights direct and indirect protection benefits when vaccinating healthy children with QLAIV in Europe, across a range of demographic structures, contact patterns and vaccination coverage rates.

History and evolution of influenza control through vaccination: from the first monovalent vaccine to universal vaccines.

Influenza is a highly infectious airborne disease with an important epidemiological and societal burden; annual epidemics and pandemics have occurred since ancient times, causing tens of millions of deaths. A hundred years after this virus was first isolated, influenza vaccines are an important influenza prevention strategy and the preparations used display good safety and tolerability profiles. Innovative tools, such as recombinant technologies and intra-dermal devices, are currently being investigated in order to improve the immunological response. The recurring mutations of influenza strains has prompted the recent introduction of a quadrivalent inactivated vaccine. In the near future, scientific research will strive to produce a long-lasting universal vaccine containing an antigen that will offer protection against all influenza virus strains.

Increasing the use of influenza vaccines in children with egg allergy

Administration of inactivated trivalent or quadrivalent influenza vaccines is now believed to be safe for individuals with egg allergy. Unless children have experienced an anaphylactic reaction to a previous dose of influenza vaccine, they can and should be immunized with a full dose of trivalent or quadrivalent inactivated vaccine.

Vaccine recommendations for children and youth for the 2014/2015 influenza season.

The Canadian Paediatric Society continues to encourage annual influenza vaccination for ALL children and youth ≥6 months of age. Recommendations from the National Advisory Committee on Immunization for the 2014/2015 influenza season include some important changes: Influenza vaccination is recommended for ALL individuals ≥6 months of age, with particular focus on those at high risk of influenza-related complications and their close contacts. Definitions of high-risk conditions and close contacts have not changed from those of 2013/2014.The preference for intranasal, live attenuated influenza vaccine (LAIV) over trivalent inactivated influenza vaccines for healthy children is restricted to individuals two to six years of age. There is insufficient evidence to recommend LAIV over trivalent inactivated influenza vaccines in older children or in children with chronic health conditions; either vaccine may be used unless there are specific contraindications.Quadrivalent influenza vaccines are expected to be available for the 2014/2015 season and may be used interchangeably with trivalent vaccines. They may offer improved protection.Trivalent or quadrivalent inactivated vaccines may be used in individuals with egg allergy; LAIV has not yet been evaluated in this population and is not recommended at this time.