Introduction Seasonal influenza causes numerous deaths worldwide each year. Annual vaccination for disease prevention is crucial. Seasonal vaccines are updated each year to closely match circulating strains. Objective To comply with European Medicines Agency (EMA) guidance, an enhanced safety study was conducted to rapidly collect and assess adverse events (AEs) within 7 days following vaccination with GSK's inactivated quadrivalent seasonal influenza vaccine (IIV4) in 2018/2019. Methods A customised AE reporting card (AERC) and standardised electronic data reporting application were used in Belgium, Germany and Spain in adult and paediatric subjects in this study. Results In 2018, 1060 subjects vaccinated with one dose of GSK's IIV4 were enrolled (all subjects in Belgium and Germany were adults, and 75% and 25% of subjects in Spain were children and adults, respectively). In Spain, 139 eligible children later received a second dose. Overall 1035 subjects completed the study. After dose 1 and dose 2, 98.3% and 100% of subjects, respectively, returned the completed AERC. Over the study period, 43.0% (456/1060 post dose 1) and 23.7% (33/139 post dose 2) of subjects reported at least one AE within 7 days after immunisation. The most frequently reported categories of AEs were General and Administration Site (e.g. injection site pain, swelling, erythema) and Respiratory Disorders (e.g. rhinorrhoea, cough, nasal congestion). There were no deaths and no serious AEs deemed related to GSK's IIV4. Conclusion In compliance with EMA guidance, this study design allowed for near real-time assessment of AEs. No safety signals were detected at any point during the study period. The study supports and confirms the acceptable safety profile of GSK's IIV4. ClinicalTrials.gov identifier NCT03688620.

Background RSV infections are frequent and can lead to respiratory complications in older adults (OA). However, there is no licensed RSV vaccine yet. Here we present immunogenicity results up to month (M) 6 after vaccination with the RSVPreF3 OA. Methods In this phase 3 multi-country ongoing study (NCT04732871), adults ≥ 60 years of age were randomized (3:1:1) to receive RSVPreF3 OA and to be followed up for 3 years. All participants received a dose of RSVPreF3 on day (D) 1. Humoral immune (HI) and cell-mediated immune (CMI) responses were measured in subsets of participants at pre-vaccination (D1), D31 and M6. HI outcomes included RSV-A and RSV-B neutralizing antibody (NAb) geometric mean titers (GMTs) and RSVPreF3-specific immunoglobulin G (IgG) antibody geometric mean concentrations (GMCs). The CMI response was assessed in terms of frequency of RSVPreF3-specific CD4+ T-cells and CD8+ T-cells expressing at least 2 activation markers including at least 1 cytokine among CD40L, 4-1BB, IL-2, TNF-α, IFN-γ, IL-13, IL-17 (polypositive T-cells). Results A total of 1653 participants received a dose of RSVPreF3 OA. Of these, 987 participants were included in the HI subset and 566 in the CMI subset at D1. The RSV-A and RSV-B GMTs and RSVPreF3-specific IgG GMCs increased between D1 and D31 followed by a decline until M6. At D31, RSV-A and RSV-B NAb GMTs were 10.5-fold and 7.8-fold higher than pre-vaccination (Figure), and RSVPreF3-specific IgG antibody GMCs was 12.2-fold higher than pre-vaccination levels. At M6, the RSV-A and RSV-B GMTs were 4.4-fold and 3.5-fold, and RSVPreF3-specific IgG antibody GMCs were 4.7-fold above pre-vaccination levels. The RSVPreF3-specific polypositive CD4+ T-cell median frequency (events/106 cells) increased from 191 (below assay quantification limit) to 1339 at D31 and declined to 666 (above assay quantification limit) by M6. No RSVPreF3-specific CD8+ T-cell response was detected after RSVPreF3 OA vaccination. Conclusion In adults ≥ 60 years of age, 1 dose of RSVPreF3 OA was shown to be immunogenic, with both high HI and specific CMI responses at D31 post-vaccination and remained 3.5–4.7 fold above pre-vaccination levels at M6. This study will continue to monitor the immunogenicity of RSVPreF3 OA up to 3 years. Funding GlaxoSmithKline Biologicals SA. Disclosures Tino F. Schwarz, Prof. Dr. MD, Biogen, Merck-Serono, Pfizer, Alexion, Bavarian Nordic, Janssen-Cilag, AstraZeneca, Biontech, MSD: Grants|GlaxoSmithKline Biologicals SA: Honoraria John E. Ervin, MD, The Alliance for Multispecialty Research – KCM: Contractual agreement for conduct of study protocol Charles Andrews, MD, GlaxoSmithKline Biologicals SA: Institutional grant|Merck and Boehringer Ingelheim: Consulting fees outside of the submitted work Delphine Collete, PhD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Magali de Heusch, PhD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Nathalie De Schrevel, PhD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Ownership Interest Bruno Salaun, PhD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Marc Lievens, MSc, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Céline Maréchal, PhD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Phoebe Nakanwagi, Master’s in Biostatistics, GlaxoSmithKline Biologicals SA: Employee Veronica Hulstrøm, PhD MD, GlaxoSmithKline Biologicals SA: Employee.

Introduction Seasonal influenza poses a major public health burden worldwide. Influenza vaccines, updated yearly to match circulating strains based on World Health Organization (WHO) recommendations, are the cornerstone of prevention and require regular monitoring. The COVID-19 pandemic is expected to cause logistical, site access and medical staff constraints and could affect the safety profile of influenza vaccines. Methods Following European Medicines Agency guidance, an enhanced safety surveillance (ESS) study assessed the frequency and severity of predefined and other adverse events (AEs) occurring within 7 days of receiving GSK’s inactivated quadrivalent seasonal influenza vaccine (IIV4), in Belgium, Germany and Spain in 2020/21, using adverse drug reaction (ADR) cards. Results During the 2020/21 influenza season, 1054 participants vaccinated with GSK’s IIV4 were enrolled (all adults in Belgium and Germany, 30% adults/70% children in Spain); 96 eligible children received a second dose. Overall, 1042 participants completed the study. After doses 1 and 2, 98.9% and 100% of participants, respectively, returned their completed ADR card. After doses 1 and 2, 37.8% (398/1054) and 13.5% (13/96) of participants, respectively, reported at least one AE. The most frequently reported categories of AEs were “general disorders and administration site conditions” (e.g. injection site pain) and “nervous system disorders” (e.g. headache). There were no deaths or serious AEs deemed related to GSK’s IIV4. Conclusion This ESS study assessed AEs in near real time. The COVID-19 pandemic did not alter the safety profile of GSK’s IIV4. No safety signals were detected during the study, which confirms the excellent safety profile of GSK’s IIV4. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00571-y.

Background RSV causes respiratory infections that can lead to serious respiratory complications in older adults (OA). Presently, there is no approved vaccine to prevent RSV infections. RSVPreF3 OA is an investigational vaccine containing 120 µg RSVPreF3 and the AS01E adjuvant. Here we show safety results up to month (M) 6 post-vaccination with RSVPreF3 OA. Methods This phase 3 multi-country ongoing study (NCT04732871) enrolled adults ≥ 60 years of age over a period of 3 years. Participants were randomized (3:1:1) to receive RSVPreF3 OA with different vaccination schedules. All participants received a dose of RSVPreF3 OA on day 1. Solicited and unsolicited adverse events (AEs) were evaluated within 4 and 30 days post-vaccination. All serious AEs (SAEs) and potential immune mediated diseases (pIMDs) were collected up to M6 post-vaccination. SAEs and pIMDs related to vaccination, and fatal AEs are collected up to study end but reported here up to M6. Results Overall, 1653 participants received a dose of RSVPreF3 OA and 1618 completed the M6 follow-up. The mean age was 70.0 (±6.6) years and 54.6% were women. The most frequently reported solicited injection site reaction within 4 days post-vaccination was pain (996 participants; 60.5%, 95% confidence interval [CI]: 58.1–62.9). Twenty-two participants (1.3%, 95% CI: 0.8–2.0) reported grade 3 pain (Figure). The most reported solicited systemic reactions were myalgia (551 participants; 33.5%, 95% CI: 31.2–35.8) and fatigue (517 participants; 31.4%, 95% CI: 29.2–33.7). Twenty-five participants (1.5%) reported fever (no grade 3). Most solicited AEs were transient lasting ∼2 days and were of mild to moderate intensity. Overall, 212 (12.8%, 95% CI: 11.3–14.5) participants reported at least 1 unsolicited AE within 30 days post-vaccination. At least 1 SAE was reported by 65 participants (3.9%, 95% CI: 3.0–5.0). Seven participants (0.4%, 95% CI: 0.2–0.9) reported at least 1 pIMD. Of the SAEs and pIMDs reported, 1 event (Guillain-Barre syndrome) was considered by the investigator as related to vaccination. Fatal SAEs were reported for 6 participants; none related to vaccination. Conclusion One dose of investigational RSVPreF3 OA vaccine was well tolerated and had an acceptable safety profile in adults ≥ 60 years of age. Funding GlaxoSmithKline Biologicals SA. Disclosures Tino F. Schwarz, Prof. Dr. MD, Biogen, Merck-Serono, Pfizer, Alexion, Bavarian Nordic, Janssen-Cilag, AstraZeneca, Biontech, MSD: Grants|GlaxoSmithKline Biologicals SA: Honoraria John E. Ervin, MD, The Alliance for Multispecialty Research – KCM: Contractual agreement for conduct of study protocol Charles Andrews, MD, GlaxoSmithKline Biologicals SA: Institutional grant|Merck and Boehringer Ingelheim: Consulting fees outside of the submitted work Miguel Vicco, PhD MD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Marc Lievens, MSc, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Céline Maréchal, PhD, GlaxoSmithKline Biologicals SA: Employee|GlaxoSmithKline Biologicals SA: Stocks/Bonds Phoebe Nakanwagi, Master’s in Biostatistics, GlaxoSmithKline Biologicals SA: Employee Veronica Hulstrøm, PhD MD, GlaxoSmithKline Biologicals SA: Employee.

Introduction Seasonal influenza infects millions annually in Europe. Annual influenza vaccination is the most effective measure to reduce the risk of infection and its complications, especially among young children and older adults. Objective We assessed adverse event (AE) frequency after receiving GSK’s inactivated quadrivalent seasonal influenza vaccine (IIV4). Methods A passive enhanced safety surveillance study was conducted in Belgium, Germany, and Spain. Adults who had received GSK's IIV4 or the parent(s)/guardian(s)/legally acceptable representative(s) of children given the vaccine were invited to complete an adverse drug reaction (ADR) card to document AEs experienced within 7 days post vaccination. Results A total of 1082 participants (51.6% females) received GSK's IIV4, including 115 children < 9 years of age who received two doses. The ADR card return rate was 97.0% ( n = 1049) after dose 1 and 100% ( n = 115) after dose 2. All participants in Belgium and Germany were adults. In Spain, 71.2% were children. After dose 1, 39.2% reported one or more AE. The most frequent AEs category was "general disorders and administration site conditions” (GDASC). AEs were most frequently reported in adults aged 18–65 years (47.2%), followed by children aged 6 months–17 years (38.1%), and adults aged > 65 years (31.6%). After dose 2, 7.8% reported one or more AE, and GDASC was again the most frequent AE category. There were no serious AEs related to GSK's IIV4 within 7 days post vaccination. Conclusion No serious AEs related to GSK’s IIV4 within 7 days post vaccination were reported. This study supports the favourable risk–benefit safety profile of GSK’s IIV4. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-021-01121-8.