Search Results (22)

Background/Objectives: Influenza poses a significant risk for young children, particularly those under five. Cell culture-derived influenza vaccines offer advantages in reducing adaptive changes and mitigating egg allergy concerns. SKYCellflu^® quadrivalent has been in use since 2015, and this study aimed to assess its safety and influenza infections in children aged 6–35 months in South Korea. Methods: A prospective cohort, non-interventional, multi-center post-marketing surveillance study was conducted from 2020 to 2024. This study presents data from the 2023–2024 influenza season on safety and influenza infections in children aged 6–35 months following SKYCellflu^® vaccination. Safety was assessed based on adverse events (AEs) within 28 days post-vaccination, and influenza infections were assessed via phone calls or medical record screening. Results: Among 333 safety set participants, 54.4% reported at least one AE, with most being mild to moderate. The cumulative incidence of influenza infections among 247 ad hoc subsets was 4.5%, and the incidence rate was 1.3 per 100 person-months (95% CI, 0.7–2.4) during the 2023–2024 influenza season. The two-dose regimen in vaccine-naïve infants aged 6–11 months showed a lower cumulative incidence of influenza infection rate (0.8% vs. 3.8%) and incidence rate (0.3 vs. 0.9 per 100 person-months) than the one-dose group (3.8%). No influenza-related hospitalizations occurred within the ad hoc subset. Conclusions: This study demonstrated a tolerable safety profile and the pattern of influenza infections following SKYCellflu^® vaccination. Additionally, the two-dose regimen was associated with a lower incidence of influenza infections, suggesting potential benefits in enhancing protection among infants aged 6–11 months. Full article

Background/Objectives: Circulating influenza strains antigenically differing from vaccine antigens increase disease burden by decreasing vaccine efficacy. Nucleoside-modified mRNA (modRNA) influenza vaccines may facilitate rapid production allowing later antigen selection and improved antigenic similarity compared to circulating strains. We studied different influenza modRNA vaccine (IRV) formulations and dose levels. Methods: This phase 1/2 randomized study evaluated IRV safety/tolerability and immunogenicity in healthy 18- through 85-year-olds. Based on safety and immunogenicity for different IRV doses, schedules, and valencies versus the quadrivalent influenza vaccine (QIV; Fluzone High-Dose Quadrivalent, Sanofi Pasteur) in phase 1 (65–85-year-olds), quadrivalent IRV (qIRV) was further evaluated in 65- through 85-year-olds and 18- through 64-year-olds in phase 2, leading to phase 3 dose selection. Results: Phase 1 (65–85-year-olds) safety/tolerability and immunogenicity findings supported qIRV 30-µg and 60-µg phase 2 assessment (18–85-year-olds, N = 610). qIRV was well tolerated. Injection site pain was the most frequently reported local reaction. Reactogenicity event incidences ≤ 7 days postvaccination for qIRV were generally higher versus QIV, observed more frequently in 18- through 64-year-olds than 65- through 85-year-olds, and showed dose-related trends (60 μg > 30 μg). qIRV and QIV adverse event profiles in 65- through 85-year-olds were similar. There were higher postvaccination hemagglutination inhibition assay geometric mean titers and fold rises and seroconversion rates observed with qIRV versus QIV for A strains, with no consistent pattern for B strains. Cell-mediated immune responses to qIRV by Day 7 showed overall higher T-cell responses against all strains versus QIV. Antibody and cell-mediated immune responses showed comparable trends across qIRV doses in 18- through 85-year-olds; a dose-related pattern was observed in 65- through 85-year-olds (60 μg > 30 μg). Conclusions: Phase 3 investigations of qIRV 60 µg in older adults and qIRV 30 µg in younger adults are warranted (ClinicalTrials.gov Identifier: NCT05052697). Full article

In this pilot study, a multi-parametric analysis comparing immune responses in sera of adult healthy subjects (HS) or people with type 2 diabetes mellitus (T2D) undergoing the single or simultaneous administration of mRNA-based COVID-19 and cellular quadrivalent inactivated influenza vaccines was conducted. While SARS-CoV-2 antibodies remains comparable, influenza antibody titers and seroconversion were significantly higher upon simultaneous vaccination. Magnitude of anti-influenza humoral response closely correlated with an early innate immune signature, previously described for the COVID-19 vaccine, composed of IL-15, IL-6, TNF-α, IFN-γ, CXCL-10 and here extended also to acute-phase protein Pentraxin 3. People with T2D receiving simultaneous vaccination showed a protective response comparable to HS correlating with the early induction of IFN-γ/CXCL10 and a significant reduction of the circulating glucose level due to increased oxidation of glucose digestion and consumption. These data, although preliminary and in-need of validation in larger cohorts, might be exploited to optimize future vaccination in people with chronic disorders, including diabetes. Full article

Influenza viruses can cause highly infectious respiratory diseases, posing noteworthy epidemic and pandemic threats. Vaccination is the most cost-effective intervention to prevent influenza and its complications. However, reliance on embryonic chicken eggs for commercial influenza vaccine production presents potential risks, including reductions in efficacy due to HA gene mutations and supply delays due to scalability challenges. Thus, alternative platforms are needed urgently to replace egg-based methods and efficiently meet the increasing demand for vaccines. In this study, we employed a baculovirus expression vector system to engineer HA, NA, and M1 genes from seasonal influenza strains A/H1N1, A/H3N2, B/Yamagata, and B/Victoria, generating virus-like particle (VLP) vaccine antigens, H1N1-VLP, H3N2-VLP, Yamagata-VLP, and Victoria-VLP. We then assessed their functional and antigenic characteristics, including hemagglutination assay, protein composition, morphology, stability, and immunogenicity. We found that recombinant VLPs displayed functional activity, resembling influenza virions in morphology and size while maintaining structural integrity. Comparative immunogenicity assessments in mice showed that our quadrivalent VLPs were consistent in inducing hemagglutination inhibition and neutralizing antibody titers against homologous viruses compared to both commercial recombinant HA and egg-based vaccines (Vaxigrip). The findings highlight insect cell-based VLP vaccines as promising candidates for quadrivalent seasonal influenza vaccines. Further studies are worth conducting. Full article

Assaying the potency of inactivated viral influenza vaccines is performed using single radial immunodiffusion, which is the globally accepted release method for potency. Under conditions of a rapidly emerging pandemic, such as the 2009 H1N1 influenza pandemic, a recognized obstacle in the delivery of vaccines to the public is the time needed for the distribution of calibrated SRID reagents (antisera and antigen standards) to vaccine manufacturers. Previously, we first described a novel streamlined MS-based assay, CombE-IDMS, which does not rely on antisera/antibodies or reference antigens, as a potential rapidly deployable alternate potency method through a comparison with SRID on adjuvanted seasonal quadrivalent vaccine cell-based (aQIVc) materials. In this report, we further demonstrate that the CombE-IDMS method can also be applied to measure the potency of pre-pandemic H5N1 and H5N8 monovalent vaccine materials, each subtype both unadjuvanted and adjuvanted, through a forced degradation study. Overall, CombE-IDMS results align with those of the gold standard SRID method on both H5N1 and H5N8 materials under conditions of thermal, pH, oxidative and freeze/thaw stress, lending further evidence for the CombE-IDMS method’s suitability as an alternate assay for potency of both seasonal and pandemic influenza vaccines. Full article

Cell-based seasonal influenza vaccine viruses may more closely match recommended vaccine strains than egg-based options. We sought to evaluate the effectiveness of seasonal cell-based quadrivalent influenza vaccine (QIVc), as reported in the published literature. A systematic literature review was conducted (PROSPERO CRD42020160851) to identify publications reporting on the effectiveness of QIVc in persons aged ≥6 months relative to no vaccination or to standard-dose, egg-based quadrivalent or trivalent influenza vaccines (QIVe/TIVe). Publications from between 1 January 2016 and 25 February 2022 were considered. The review identified 18 relevant publications spanning three influenza seasons from the 2017–2020 period, with an overall pooled relative vaccine effectiveness (rVE) of 8.4% (95% CI, 6.5–10.2%) for QIVc vs. QIVe/TIVe. Among persons aged 4–64 years, the pooled rVE was 16.2% (95% CI, 7.6–24.8%) for 2017–2018, 6.1% (4.9–7.3%) for 2018–2019, and 10.1% (6.3–14.0%) for 2019–2020. For adults aged ≥65 years, the pooled rVE was 9.9% (95% CI, 6.9–12.9%) in the egg-adapted 2017–2018 season, whereas there was no significant difference in 2018–2019. For persons aged 4–64 years, QIVc was consistently more effective than QIVe/TIVe over the three influenza seasons. For persons aged ≥65 years, protection with QIVc was greater than QIVe or TIVe during the 2017–2018 season and comparable in 2018–2019. Full article

Cell-based manufacturing of seasonal influenza vaccines eliminates the risk of egg-adaptation of candidate vaccine viruses, potentially increasing vaccine effectiveness (VE). We present an overview of published data reporting the VE and cost-effectiveness of a cell-based quadrivalent influenza vaccine (QIVc) in preventing influenza-related outcomes in the pediatric population. We identified 16 clinical studies that included data on the VE of a QIVc or the relative VE (rVE) of a QIVc versus an egg-based QIV (QIVe) in children and/or adolescents, 11 of which presented estimates specifically for the pediatric age group. Of these, two studies reported rVE against hospitalizations. Point estimates of rVE varied from 2.1% to 33.0%, with studies reporting significant benefits of using a QIVc against influenza-related, pneumonia, asthma, and all-cause hospitalization. Four studies reported rVE against influenza-related medical encounters, with point estimates against non-strain specific encounters ranging from 3.9% to 18.8% across seasons. One study evaluated rVE against any influenza, with variable results by strain. The other four studies presented VE data against laboratory-confirmed influenza. Three health economics studies focusing on a pediatric population also found the use of QIVc to be cost-effective or cost-saving. Overall, using a QIVc is effective in pediatric patients, with evidence of incremental benefits over using a QIVe in preventing hospitalizations and influenza-related medical encounters in nearly all published studies. Full article

To ensure that vaccination offers the best protection against an infectious disease, sequence identity between the vaccine and the circulating strain is paramount. During replication of nucleic acid, random mutations occur due to the level of polymerase fidelity. In traditional influenza vaccine manufacture, vaccine viruses are propagated in fertilized chicken eggs, which can result in egg-adaptive mutations in the antigen-encoding genes. Whilst this improves infection and replication in eggs, mutations may reduce the effectiveness of egg-based influenza vaccines against circulating human viruses. In contrast, egg-adaptive mutations are avoided when vaccine viruses are propagated in Madin-Darby canine kidney (MDCK) cell lines during manufacture of cell-based inactivated influenza vaccines. The first mammalian cell-only strain was included in Flucelvax^® Quadrivalent in 2017. A sequence analysis of the viruses selected for inclusion in this vaccine (n = 15 vaccine strains, containing both hemagglutinin and neuraminidase) demonstrated that no mutations occur in the antigenic sites of either hemagglutinin or neuraminidase, indicating that cell adaptation does not occur during production of this cell-based vaccine. The development of this now entirely mammalian-based vaccine system, which incorporates both hemagglutinin and neuraminidase, ensures that the significant protective antigens are equivalent to the strains recommended by the World Health Organization (WHO) in both amino acid sequence and glycosylation pattern. The inclusion of both proteins in a vaccine may provide an advantage over recombinant vaccines containing hemagglutinin alone. Findings from real world effectiveness studies support the use of cell-based influenza vaccines. Full article

Influenza A virus is a respiratory pathogen that is responsible for regular epidemics and occasional pandemics that result in substantial damage to life and the economy. The yearly reformulation of trivalent or quadrivalent flu vaccines encompassing surface glycoproteins derived from the current circulating strains of the virus does not provide sufficient cross-protection against mismatched strains. Unlike the current vaccines that elicit a predominant humoral response, vaccines that induce CD8⁺ T cells have demonstrated a capacity to provide cross-protection against different influenza strains, including novel influenza viruses. Immunopeptidomics, the mass spectrometric identification of human-leukocyte-antigen (HLA)-bound peptides isolated from infected cells, has recently provided key insights into viral peptides that can serve as potential T cell epitopes. The critical elements required for a strong and long-living CD8⁺ T cell response are related to both HLA restriction and the immunogenicity of the viral peptide. This review examines the importance of HLA and the viral immunopeptidome for the design of a universal influenza T-cell-based vaccine. Full article

In 2021–2022, influenza vaccine coverage in the US dropped below pre-COVID-19 pandemic levels. Cocirculation of COVID-19 and influenza could place a substantial burden on hospital utilization in future seasons, particularly given the reduced exposure to influenza during the pandemic. We used a dynamic susceptible-exposed-infected-recovered model to simulate influenza transmission with varying influenza vaccine coverage against a background of COVID-19 circulation, in order to estimate acute and ICU hospital bed occupancy for both diseases. We evaluated two vaccine scenarios: egg-based quadrivalent influenza vaccine (QIVe) for all age groups or cell-based QIV (QIVc) for 0.5–64 year-olds with adjuvanted QIV (aQIV) for ≥65 year-olds. ICU bed availability was more limiting than general hospital bed availability, with a vaccine coverage of ≥70% required to avoid negatively impacting ICU bed availability in a high-incidence influenza season. The timing of disease peaks was a key factor together with vaccine coverage, with a difference of ≥50 days needed between peak influenza and COVID-19 bed usage together with 65% influenza vaccine coverage to avoid negative impacts. QIVc + aQIV resulted in lower bed occupancy which, while not substantial, may be critical in very high hospital resource usage situations. In a situation with co-circulating influenza and COVID-19, proactive vaccination planning could help to avert overwhelming healthcare systems in upcoming influenza seasons. Full article

Background: Quadrivalent cell-based influenza vaccines (QIVc) avoid egg-adaptive mutations and can be more effective than traditional quadrivalent egg-based influenza vaccines (QIVe). This analysis compared the cost-effectiveness of QIVc and QIVe in Argentinian populations < 65 years old from the payer and societal perspectives. Methods: A static decision tree model compared the costs and health benefits of vaccination with QIVc vs. QIVe using a one-year time horizon. The relative vaccine effectiveness of QIVc vs. QIVe was assumed to be 8.1% for children and 11.4% for adults. An alternative high egg-adaptation scenario was also assessed. Model inputs were sourced from Argentina or the international literature. Deterministic and probabilistic sensitivity analyses were performed. Results: Compared to QIVe, QIVc would prevent 17,857 general practitioner visits, 2418 complications, 816 hospitalizations, and 12 deaths per year. From the payers’ perspective, the incremental cost-effectiveness ratio per quality-adjusted life years gained was USD12,214 in the base case and USD2311 in the high egg-adaptation scenario. QIVc was cost-saving from the societal perspective in both scenarios. Conclusions: QIVc in Argentina would be cost-effective relative to QIVe. The potential health benefits and savings would be even higher in high egg-adaptation seasons. Full article

Objective: To evaluate pregnancy and infant outcomes among persons immunized with a cell-based quadrivalent inactivated influenza vaccine (IIV4c) during routine pregnancy care. Design: Prospective observational cohort. Setting: US-based obstetrics/gynecology clinics. Population: Pregnant persons. This US-based, prospective observational cohort study evaluated the safety of quadrivalent inactivated influenza vaccine (IIV4c; Flucelvax^® Quad) in pregnant persons immunized over 3 influenza seasons between 2017 and 2020. Pregnant persons were immunized with IIV4c as part of routine care, after which their health care provides HCPs with all observational data to a single coordinating center. Follow-up data were collected at the end of the second trimester and/or at the time of pregnancy outcome. A scientific advisory committee reviewed the data. Prevalence point estimates were reported with 95% confidence intervals (CIs). Pregnancy outcomes included: live birth, stillbirth, spontaneous abortion, elective termination, and maternal death. Infant outcomes included: preterm birth (<37 weeks gestational age), low birth weight (<2500 g), or major congenital malformations (MCMs). Of the 665 evaluable participants, 659 (99.1%) had a live birth. No stillbirths (0% [95% CI 0.0–0.6]), 4 spontaneous abortions (1.9% [0.5–4.8]), and 1 elective termination (0.5% [0.0–2.6]) were reported. Among 673 infants, 9.2% (upper 95% CI 11.5%) were born prematurely, 5.8% (upper 95% CI 7.6%) had low birth weight, and 1.9% (upper 95% CI 3.1%) were reported to have an MCM. No maternal deaths were reported. Of the 2 infants who died shortly after birth, one was adjudicated as not related to the vaccine; the other’s cause could not be determined due to maternal loss to follow-up. The prevalence of adverse pregnancy outcomes or preterm birth, low birth weight, or MCMs in newborns was similar in persons vaccinated with IIV4c compared to the rates observed in US surveillance systems. The safety profile of IIV4c in pregnant persons is consistent with previously studied influenza vaccines. Full article

In Canada, approximately 12,000 people annually are hospitalized with influenza. While vaccination is the most effective method for reducing the burden of seasonal influenza, the propagation of vaccine virus strains in eggs can result in egg adaption, resulting in reduced antigenic similarity to circulating strains and thus lower vaccine effectiveness (VE). Cell-based propagation methods avoid these alterations and therefore may be more effective than egg-propagation vaccines. We evaluated three different scenarios: (1) egg-based quadrivalent influenza vaccine (QIVe) for individuals <65 years and adjuvanted trivalent influenza vaccine (aTIV) for ≥65 years; (2) QIVe (<65 years) and high-dose QIV (HD −; QIV; ≥65 years); and (3) cell-based derived QIV (QIVc; <65 years) and aTIV (≥65 years) compared with a baseline scenario of QIVe for all age groups. Modelling was performed using a dynamic age-structured SEIR model, which assessed each strain individually using data from the 2012–2019 seasons. Probabilistic sensitivity analysis assessed the robustness of the results with respect to variation in absolute VE, relative VE, number of egg-adapted seasons, and economic parameters. QIVe + aTIV was cost-saving compared with the baseline scenario (QIVe for all), and QIVe + HD − QIV was not cost-effective in the majority of simulations, reflecting the high acquisition cost of HD − QIV. Overall, while the incremental benefits may vary by influenza season, QIVc + aTIV resulted in the greatest reductions in cases, hospitalizations, and mortality, and was cost-effective (ICER < CAD 50,000) in all simulations. Full article

Vaccination is the most effective intervention to prevent influenza. Adults at risk of complications are among the targets of the vaccination campaigns and can be vaccinated with different types of quadrivalent influenza vaccines (QIVs). In the light of assessing the relative immunogenicity and efficacy of different QIVs, a systematic review was performed. Randomized controlled trials conducted in adults aged 18–64 years until 30 March 2021 were searched through three databases (Medline, Cochrane Library and Scopus). Twenty-four RCTs were eventually included. After data extraction, a network meta-analysis was not applicable due to the lack of common comparators. However, in the presence of at least two studies, single meta-analyses were performed to evaluate immunogenicity and efficacy; on the contrary, data from single studies were considered. Seroconversion rate for H1N1 was higher for standard QIVs, while for the remaining strains it was higher for low-dose adjuvanted QIVs. For seroprotection rate, the recombinant vaccine recorded the highest values for H3N2, while for the other strains, the cell-based QIVs achieved better results. In general, standard and cell-based QIVs showed an overall good immunogenicity profile. Nevertheless, as a relative comparative analysis was not possible, further research would be deserved. Full article

The adaptation of influenza seed viruses in egg culture can result in a variable antigenic vaccine match each season. The cell-based quadrivalent inactivated influenza vaccine (IIV4c) contains viruses grown in mammalian cell lines rather than eggs. IIV4c is not subject to egg-adaptive changes and therefore may offer improved protection relative to egg-based vaccines, depending on the degree of match with circulating influenza viruses. We summarize the relative vaccine effectiveness (rVE) of IIV4c versus egg-based quadrivalent influenza vaccines (IIV4e) to prevent influenza-related medical encounters (IRMEs) from three retrospective observational cohort studies conducted during the 2017–2018, 2018–2019, and 2019–2020 US influenza seasons using the same underlying electronic medical record dataset for all three seasons—with the addition of linked medical claims for the latter two seasons. We identified IRMEs using diagnostic codes specific to influenza disease (ICD J09*-J11*) from the records of over 10 million people. We estimated rVE using propensity score methods adjusting for age, sex, race, ethnicity, geographic location, week of vaccination, and health status. Subgroup analyses included specific age groups. IIV4c consistently had higher relative effectiveness than IIV4e across all seasons assessed, which were characterized by different dominant circulating strains and variable antigenic drift or egg adaptation. Full article