Immunogenicity and safety following one dose of AS01E-adjuvanted respiratory syncytial virus prefusion F protein vaccine in older adults: a phase 3 trial.

BACKGROUND: The recently approved AS01E-adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) demonstrated high efficacy against RSV-related disease in ≥60-year-olds. METHODS: This ongoing phase 3 study in ≥60-year-olds evaluates the immune persistence until three years post-RSVPreF3 OA vaccination. Here, we describe interim results on humoral and cell-mediated immunogenicity, reactogenicity, and safety until one year post-dose 1. RESULTS: In total, 1653 participants were vaccinated. One month post-dose 1, neutralization titers increased 10.5-fold (RSV-A) and 7.8-fold (RSV-B) versus pre-dose 1. Titers then declined to levels 4.4-fold (RSV-A) and 3.5-fold (RSV-B) above pre-dose 1 at month 6, and remained 3.1-fold (RSV-A) and 2.3-fold (RSV-B) above pre-dose 1 levels after one year. RSVPreF3-binding immunoglobulin G levels and CD4+ T-cell frequencies showed similar kinetics. Solicited administration-site and systemic adverse events (mostly mild to moderate and transient) were reported by 62.2% and 49.5% of participants. Serious adverse events were reported by 3.9% of participants within 6 months post-dose 1; one case was considered vaccine-related. CONCLUSIONS: One RSVPreF3 OA dose elicited cell-mediated and RSV-A and RSV-B-specific humoral immune responses that declined over time but remained above pre-dose 1 levels for at least one year. The vaccine was well tolerated with an acceptable safety profile.Clinicaltrials.gov NCT04732871.

Respiratory syncytial virus (RSV) is a major cause of illness and hospitalization in older adults. An RSV vaccine for older adults developed by GSK was recently approved. The vaccine was well tolerated and provided protection against RSV disease in adults aged 60 years and older during at least one RSV season. In this ongoing study, we are evaluating the magnitude and durability of the immune response, as well as vaccine safety, until three years after vaccination of adults aged 60 years and older from five countries. Here, we report the results of an interim analysis until one year after vaccination with one dose. In total, 1653 participants were vaccinated. We found that the vaccine induced a strong immune response that was evident one month after vaccination, after which it declined, but persisted for at least one year. Study participants most often reported pain at the injection site, muscle pain, tiredness, and headache as adverse reactions, which were mostly mild to moderate and of short duration. One serious adverse reaction was considered related to the vaccine. The long-term immune response that was observed in this study is consistent with the vaccine providing protection during at least one RSV season.

Enhanced safety surveillance of GSK's quadrivalent seasonal influenza vaccine in Germany and Spain (2021/2022 season) using an electronic patient-reported outcome system for vaccine safety remote monitoring.

BACKGROUND: Seasonal influenza epidemics are managed through vaccination each winter in the European Union, to prevent infections, complications, and deaths. As circulating virus strains vary unpredictably, vaccines are reformulated annually, and their safety monitored rapidly and continuously at the start of each season, following European Medicines Agency guidelines.Seasonal influenza epidemics are managed through vaccination each winter in the European Union, to prevent infections, complications, and deaths. As circulating virus strains vary unpredictably, vaccines are reformulated annually, and their safety monitored rapidly and continuously at the start of each season, following European Medicines Agency guidelines. METHODS: This enhanced safety surveillance study assessed pre-specified and other adverse events (AEs) occurring within 7 days of GSK's inactivated quadrivalent seasonal influenza vaccine (IIV4) in children and adults in Spain and Germany. As the study was conducted during the COVID-19 pandemic (2021/2022 season), data were collected electronically, using a web portal or call center. RESULTS: Safety was assessed in 737 participants (median age 49 and 9 years in Germany and Spain, respectively, 19.3% with a chronic medical condition). After Dose 1 and Dose 2, respectively, 332 (45.1%) and 5 (26.3%) participants reported at least one AE, primarily pre-specified AEs. The most common AEs after Dose 1 (adults and children) were injection site pain, swelling or erythema, headache, and fatigue. After Dose 2 (in children), the most common AEs were injection site pain, rhinorrhea, fatigue, and decreased appetite. No new or unexpected safety issues were identified. CONCLUSION: This study supports and confirms the safety profile of GSK's IIV4 in all age groups with a vaccine indication. The new electronic safety reporting method (with response rates of 75.4% following Dose 1 and 100% following Dose 2) provides an alternative for future studies to reduce the burden on sites or in case site visits are not feasible.

Brand-Specific Enhanced Safety Surveillance Study of GSK's Quadrivalent Seasonal Influenza Vaccine, Conducted During the COVID-19 Pandemic, in Belgium, Germany and Spain, for the 2020/21 Season.

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.

The Adjuvanted Recombinant Zoster Vaccine Confers Long-Term Protection Against Herpes Zoster: Interim Results of an Extension Study of the Pivotal Phase 3 Clinical Trials ZOE-50 and ZOE-70.

BACKGROUND: This ongoing follow-up study evaluated the persistence of efficacy and immune responses for 6 additional years in adults vaccinated with the glycoprotein E (gE)-based adjuvanted recombinant zoster vaccine (RZV) at age ≥50 years in 2 pivotal efficacy trials (ZOE-50 and ZOE-70). The present interim analysis was performed after ≥2 additional years of follow-up (between 5.1 and 7.1 years [mean] post-vaccination) and includes partial data for year (Y) 8 post-vaccination. METHODS: Annual assessments were performed for efficacy against herpes zoster (HZ) from Y6 post-vaccination and for anti-gE antibody concentrations and gE-specific CD4[2+] T-cell (expressing ≥2 of 4 assessed activation markers) frequencies from Y5 post-vaccination. RESULTS: Of 7413 participants enrolled for the long-term efficacy assessment, 7277 (mean age at vaccination, 67.2 years), 813, and 108 were included in the cohorts evaluating efficacy, humoral immune responses, and cell-mediated immune responses, respectively. Efficacy of RZV against HZ through this interim analysis was 84.0% (95% confidence interval [CI], 75.9-89.8) from the start of this follow-up study and 90.9% (95% CI, 88.2-93.2) from vaccination in ZOE-50/70. Annual vaccine efficacy estimates were >84% for each year since vaccination and remained stable through this interim analysis. Anti-gE antibody geometric mean concentrations and median frequencies of gE-specific CD4[2+] T cells reached a plateau at approximately 6-fold above pre-vaccination levels. CONCLUSIONS: Efficacy against HZ and immune responses to RZV remained high, suggesting that the clinical benefit of RZV in older adults is sustained for at least 7 years post-vaccination. Clinical Trials Registration. NCT02723773.

Safety Profile of GSK's Inactivated Quadrivalent Seasonal Influenza Vaccine in Belgium, Germany and Spain: Passive Enhanced Safety Surveillance Study for the 2019/2020 Influenza Season.

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.

Seasonal influenza infects millions annually in Europe, especially young children and older adults. Annual influenza vaccination is the most effective measure to reduce the risk of infection and its complications. As the wild influenza virus strains change every year, the composition of the influenza vaccine changes as well. Since the vaccine is produced in the same way over the years, extensive safety studies are no longer required by regulatory authorities. Instead, monitoring of any unwanted medical incidents (adverse events) after vaccination is required. For the 2019/2020 season, we monitored the adverse events reported by a representative sample of people in Belgium, Germany, and Spain within 7 days after receiving GSK's seasonal influenza vaccine.Of the 1082 people who received the first dose of the vaccine, 39% reported at least one adverse event, such as pain and swelling at the injection site, tiredness, fever, headache, or dizziness. A total of 115 children under 9 years of age received two doses 4 weeks apart. After their second dose, few of these children (8%) reported adverse events. The most frequent adverse events were fever, swelling and pain at the injection site, runny nose, or irritability. No serious adverse events were reported after either the first or second dose.No serious adverse events related to GSK's seasonal influenza vaccine within the 7 days after vaccination were reported. This study supports the favourable risk­benefit safety profile of GSK's seasonal influenza vaccine.

Brand-Specific Enhanced Safety Surveillance of GSK's Quadrivalent Seasonal Influenza Vaccine in Belgium, Germany and Spain for the 2018/2019 Season.

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.