A Real-World Clinical and Economic Analysis of Cell-derived Quadrivalent Influenza Vaccine Compared to Standard Egg-derived Quadrivalent Influenza Vaccines During the 2019-20 Influenza Season in the United States

Background Cell-derived influenza vaccines are not subject to egg adaptive mutations that have potential to decrease vaccine effectiveness. This retrospective analysis estimated the relative vaccine effectiveness (rVE) of cell-derived quadrivalent influenza vaccine (IIV4c) compared to standard egg-derived quadrivalent influenza vaccines (IIV4e) among recipients aged 4-64 years in the US during the 2019-20 influenza season. Methods The IQVIA PharMetrics® Plus administrative claims database was utilized. Study outcomes were assessed post-vaccination through the end of the study period (March 7, 2020). Inverse probability of treatment weighting (IPTW) was implemented to adjust for covariate imbalance. Adjusted rVE against influenza-related hospitalizations/emergency room (ER) visits and other clinical outcomes was estimated through IPTW-weighted Poisson regression models for the IIV4c and IIV4e cohorts and for the subgroup with ≥1 high-risk condition. Sensitivity analyses modifying the outcome assessment period as well as a doubly-robust analysis were also conducted. IPTW-weighted generalized linear models were used to estimate predicted annualized all-cause costs. Results The final sample comprised 1,138,969 IIV4c and 3,926,357 IIV4e recipients following IPTW adjustment. IIV4c was more effective in preventing influenza-related hospitalizations/ER visits as well as respiratory-related hospitalizations/ER visits compared to IIV4e. IIV4c was also more effective for the high-risk subgroup and across the sensitivity analyses. IIV4c was also associated with significantly lower annualized all-cause total costs compared to IIV4e (-$467), driven by lower costs for outpatient medical services and inpatient hospitalizations. Conclusions IIV4c was significantly more effective in preventing influenza-related hospitalizations/ER visits compared to IIV4e and was associated with significantly lower all-cause costs.

1341. Relative Vaccine Effectiveness Against Influenza-related Hospitalizations and Respiratory Events During the 2019/20 Influenza seAson in U.S. Children and Adults. A Real-World Evidence Comparison Between Quadrivalent Cell-based and Egg-based Influenza Vaccines

Background Non-egg-based influenza vaccine manufacturing reduces egg adaptation and therefore has the potential to increase vaccine effectiveness. This study evaluated whether the cell-based quadrivalent influenza vaccine (QIVc) improved relative vaccine effectiveness (rVE) compared to standard-dose egg-based quadrivalent influenza vaccine (QIVe-SD) in the reduction of influenza-related and respiratory-related hospitalizations/emergency room (ER) visits among subjects 4-64 years old during the 2019/20 influenza season. Methods A retrospective analysis was conducted among subjects 4-64 years old vaccinated with QIVc or QIVe-SD using administrative claims data in the United States of America (U.S.) (IQVIA PharMetrics® Plus). Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounders. Post-IPTW, the number of events and rates (per 1,000 vaccinated subject-seasons) of influenza-related hospitalizations/ER visits, respiratory-related hospitalizations/ER visits and all-cause hospitalizations were assessed. Poisson regression was used to estimate adjusted rVE. To avoid any influenza outcome misclassification with COVID-19 infection, the study period ended March 7,2020. A sub-analysis for a high-risk subgroup was conducted. Urinary tract infection (UTI) hospitalization was assessed as a negative control endpoint. Results During the 2019/20 influenza season, 1,150,134 QIVc and 3,924,819 QIVe-SD recipients were identified post-IPTW. Overall adjusted analyses (4-64 years old) found that QIVc was associated with a significantly higher rVE compared to QIVe-SD against influenza-related hospitalizations/ER visits (5.3% [95% CI: 0.5%-9.9%]), all-cause hospitalizations (14.5% [95% CI: 13.1%-15.8%]) and any respiratory-related hospitalization/ER visit (8.2% [95% CI: 6.5%-9.8%]). A similar trend was seen for the high-risk subgroup; for instance, rVE for QIVc compared to QIVe-SD against influenza-related hospitalizations/ER visits was 10.5% [95% CI: 2.9%-17.4%]. No effect was identified for the negative control outcome. Conclusion QIVc was significantly more effective in preventing influenza-related and respiratory-related hospitalizations/ER visits, as well as all-cause hospitalizations, compared to QIVe-SD. Disclosures Stephen I. Pelton, MD, Seqirus (Consultant) Maarten Postma, Dr., Seqirus (Consultant) Victoria Divino, PhD, Seqirus (Consultant) Joaquin F. Mould-Quevedo, PhD, Seqirus (Employee) Ruthwik Anupindi, PhD, Seqirus (Consultant) Mitchell DeKoven, PhD, Seqirus (Consultant) myron J. levin, MD, GSK group of companies (Employee, Research Grant or Support)

Safety and immunogenicity of a high-dose quadrivalent influenza vaccine administered concomitantly with a third dose of the mRNA-1273 SARS-CoV-2 vaccine in adults ≥ 65 years of age: a Phase II, open-label study

Background Concomitant seasonal influenza vaccination with a COVID-19 vaccine booster could help to minimise potential disruption to the seasonal influenza vaccination campaign and maximise protection against both diseases among individuals at risk of severe disease and hospitalisation. This study assesses the safety and immunogenicity of concomitant administration of high-dose quadrivalent influenza vaccine (QIV-HD) and a mRNA-1273 vaccine booster dose in older adults. Methods This is an ongoing Phase II, multi-centre, open-label study (NCT04969276). We describe interim results up to 21 days after vaccination (July 2021–August 2021). Adults aged ≥ 65 years living in the community, who were to have received a second mRNA-1273 dose at least five months previously, were randomised (1:1:1) to concomitant QIV-HD and mRNA-1273 vaccination (Coad), QIV-HD alone, or mRNA-1273 vaccine alone. Unsolicited adverse events (AEs) occurring immediately, solicited local and systemic reactions up to day (D)8, and unsolicited AEs, serious AEs (SAEs), AEs of special interest (AESIs) and medically attended AEs (MAAEs) up to D22 were reported. Haemagglutination inhibition (HAI) antibody responses to influenza A/H1N1, A/H3N2, B/Yamagata and B/Victoria strains and SARS CoV-2 binding antibody responses (SARS-CoV-2 Pre-Spike IgG ELISA) were assessed at D1 and D22. Findings Of 306 participants randomised, 296 were included for analysis (Coad, n=100; QIV-HD, n=92; mRNA-1273, n=104). Reactogenicity profiles were similar between the Coad and mRNA-1273 groups, with lower reactogenicity rates in the QIV-HD group (frequency [95% CIs] of solicited injection site reactions: 86·0% [77·6–92·1], 91·3% [84·2–96·0] and 61·8% [50·9–71·9] ; solicited systemic reactions: 80·0% [70·8–87·3], 83·7% [75·1–90·2] and 49·4% [38·7–60·2], respectively). Up to D22, unsolicited AEs were reported for 17·0% and 14·4% participants in the Coad and mRNA-1273 groups, respectively, with a lower rate (10·9%) in the QIV-HD group. Seven MAAEs were reported (Coad, n=3; QIV-HD, n=1; mRNA-1273, n=3). There were no SAEs, AESIs or deaths. HAI antibody geometric mean titres (GMTs) increased from D1 to D22 to similar levels for each influenza strain in the Coad and QIV-HD groups (GMTs [95% confidence interval], range across strains: Coad, 286 [233–352] to 429 [350–525] ; QIV-HD, 315 [257–386] to 471 [378–588]). SARS-CoV-2 binding antibody geometric mean concentrations (GMCs) also increased to similar levels in the Coad and mRNA-1273 groups (D22 GMCs [95% confidence interval]: 7634 [6445–9042] and 7904 [6883–9077], respectively). Interpretation No safety concerns or immune interference were observed for concomitant administration of QIV-HD with mRNA-1273 booster in adults aged ≥ 65 years, supporting co-administration recommendations.

The Epidemiological and Economic Impact of a Cell-Based Quadrivalent Influenza Vaccine in Adults in the US: A Dynamic Modeling Approach

Mutations of the H3N2 vaccine strain during the egg-based vaccine manufacturing process partly explain the suboptimal effectiveness of traditional seasonal influenza vaccines. Cell-based influenza vaccines improve antigenic match and vaccine effectiveness by avoiding such egg-adaptation. This study evaluated the public health and economic impact of a cell-based quadrivalent influenza vaccine (QIVc) in adults (18–64 years) compared to the standard egg-based quadrivalent influenza vaccine (QIVe) in the US. The impact of QIVc over QIVe in public health and cost outcomes was estimated using a dynamic age-structured SEIR transmission model, which accounted for four circulating influenza strains [A/H1N1pdm9, A/H3N2, B(Victoria), and B(Yamagata)] and was calibrated on the 2013–2018 influenza seasons. The robustness of the results was assessed in univariate and probabilistic sensitivity analyses. Switching from QIVe to QIVc in 18- to 64-year-olds may prevent 5.7 million symptomatic cases, 1.8 million outpatient visits, 50,000 hospitalizations, and 5453 deaths annually. The switch could save 128,000 Quality-Adjusted Life Years (QALYs) and US $ 845 M in direct costs, resulting in cost-savings in a three-year time horizon analysis. Probabilistic sensitivity analyses confirmed the robustness of the cost-saving result. The analysis shows that QIVc is expected to prevent hospitalizations and deaths, and result in substantial savings in healthcare costs.