Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus Vaccine in Infants 6-7 Months of age: A Phase 1/2 Randomized Trial.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. METHODS: Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. RESULTS: Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post-ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post-dose 2. CONCLUSIONS: ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration. NCT03636906.

A terrestrial planet candidate in a temperate orbit around Proxima Centauri.

At a distance of 1.295 parsecs, the red dwarf Proxima Centauri (α Centauri C, GL 551, HIP 70890 or simply Proxima) is the Sun's closest stellar neighbour and one of the best-studied low-mass stars. It has an effective temperature of only around 3,050 kelvin, a luminosity of 0.15 per cent of that of the Sun, a measured radius of 14 per cent of the radius of the Sun and a mass of about 12 per cent of the mass of the Sun. Although Proxima is considered a moderately active star, its rotation period is about 83 days (ref. 3) and its quiescent activity levels and X-ray luminosity are comparable to those of the Sun. Here we report observations that reveal the presence of a small planet with a minimum mass of about 1.3 Earth masses orbiting Proxima with a period of approximately 11.2 days at a semi-major-axis distance of around 0.05 astronomical units. Its equilibrium temperature is within the range where water could be liquid on its surface.

Immunogenicity and safety of porcine circovirus-free human rotavirus vaccine in healthy infants: a phase III, randomized trial.

BACKGROUND: Porcine circovirus type 1 (PCV-1) material was detected in the human rotavirus vaccine (HRV) in 2010. In this study (NCT02914184) we compared immunogenicity and safety of the PCV-free HRV vaccine (PCV-free HRV) with HRV. PCV-free HRV is an HRV with no detection of PCV-1 and PCV-2 according to the limit of detection of the tests used. METHODS: Healthy infants 6-12 weeks of age were randomized (1:1:1:1) to receive 2 doses of 1 of the 3 lots of PCV-free HRV or HRV. The study objectives were to demonstrate lot-to-lot consistency of the PCV-free HRV and non-inferiority of PCV-free HRV as compared to HRV in terms of immunogenicity, 1-2 months post-dose 2. Reactogenicity and safety were also assessed. RESULTS: Overall, 1612 infants were enrolled and 1545 completed the study. Study objectives were demonstrated since the pre-defined criteria were met. Among participants receiving PCV-free HRV and HRV, 79.27% and 81.76% seroconverted and geometric mean concentrations were 159.5 and 152.8 U/mL, respectively. The incidences of adverse events and serious adverse events were similar between the pooled PCV-free HRV and HRV groups. CONCLUSIONS: The 3 PCV-free HRV lots demonstrated consistency and PCV-free HRV was non-inferior compared to HRV in terms of immunogenicity.

Immunogenicity and safety of an inactivated quadrivalent influenza vaccine candidate: a phase III randomized controlled trial in children.

BACKGROUND: Mismatch between circulating influenza B viruses (Yamagata and Victoria lineages) and vaccine strains occurs frequently. METHODS: In a randomized controlled trial, immunogenicity and safety of an inactivated quadrivalent influenza vaccine candidate (QIV) versus trivalent inactivated influenza vaccine (TIV)-Victoria(Vic) and TIV-Yamagata(Yam) in children 3-17 years of age was evaluated. In an open-label study arm, QIV only was assessed in children 6-35 months of age. RESULTS: A total of 3094 children (932 QIV, 929 TIV-Vic, 932 TIV-Yam, and 301 QIV only) were vaccinated. QIV was noninferior to the TIVs for shared strains (A/H3N2 and A/H1N1) based on hemagglutination-inhibition (HI) antibodies 28 days after last vaccination, and superior for the unique B strains Victoria and Yamagata (geometric mean titer ratios 2.61, 3.78; seroconversion rate differences 33.96%, 44.63%). Among children in the randomized trial, adverse event rates were similar except for injection site pain (dose 1: 65.4% QIV, 54.6% TIV-Vic, 55.7% TIV-Yam). CONCLUSION: QIV elicited superior HI responses to the added B strains compared to TIV controls, potentially improving its effectiveness against influenza B. HI responses were similar between QIV and TIV controls for the shared strains. QIV had an acceptable safety profile relative to TIVs. CLINICAL TRIALS REGISTRATION: NCT01198756.

Disparate kinetics in immune response of two different Haemophilus influenzae type b conjugate vaccines: Immunogenicity and safety observations from a randomized controlled phase IV study in healthy infants and toddlers using a 2+1 schedule.

Since the introduction of Haemophilus Influenzae type b (Hib) conjugate vaccines, invasive Hib disease has strongly declined worldwide, yet continued control of Hib disease remains important. In Europe, currently three different hexavalent combination vaccines containing Hib conjugates are marketed. In this phase IV, single-blind, randomized, controlled, multi-country study (NCT04535037), we aimed to compare, in a 2 + 1 vaccination schedule, the immunogenicity and safety and show non-inferiority, as well as superiority, of DTPa-HBV-IPV/Hib (Ih group) versus DTaP5-HB-IPV-Hib (Va group) in terms of anti-polyribosylribitol phosphate (PRP) antibody geometric mean concentrations (GMCs) and proportion of participants reaching anti-PRP antibody concentrations greater than or equal to a threshold of 5 µg/mL. One month after the booster vaccination, the anti-PRP antibody GMC ratio (Ih group/Va group) was 0.917 (95% CI: 0.710-1.185), meeting the non-inferiority criteria. The difference in percentage of participants (Ih group - Va group) reaching GMCs ≥5 µg/mL was -6.3% (95% CI: -14.1% to 1.5%), not reaching the predefined non-inferiority threshold. Interestingly, a slightly higher post-booster antibody avidity was observed in the Ih group versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. This study illustrates the different kinetics of the anti-PRP antibody response post-primary and post-booster using the two vaccines containing different Hib conjugates and indicates a potential differential impact of concomitant vaccinations on the anti-PRP responses. The clinical implications of these differences should be further studied.

Vaccination against Haemophilus influenzae type b (Hib) is included in the majority of national immunization programs worldwide and has shown to be effective in preventing Hib disease. In Europe, different vaccines containing Hib components are marketed. We compared the immune response and safety of 2 of these (DTPa-HBV-IPV/Hib, Ih group) and DTaP5-HB-IPV-Hib, Va group) in infants and toddlers, when used in a 2 + 1 schedule, i.e. two primary vaccination doses (at 2 and 4 months of age of the infant), followed by one booster dose at the age of one year. One month after the booster vaccination, the antibody concentration ratio between both groups (Ih group/Va group) was 0.917 (95% CI: 0.710­1.185) showing the DTPa-HBV-IPV/Hib vaccine was non-inferior to the DTaP5-HB-IPV-Hib vaccine; the difference in percentage of participants (Ih group ­ Va group) with antibody concentrations above 5 µg/mL was -6.3% (95% CI: −14.1% to 1.5%), which did not meet the pre-defined criterion for non-inferiority. In the Ih group, the quality of antibodies produced was somewhat higher versus the Va group. Both vaccines were well tolerated, and no safety concerns were raised. The kinetics of the immune response are different between the 2 vaccines. Since both vaccines contain different additional components (conjugated proteins), a possible effect of concomitant (simultaneously administered) vaccines was studied. Further investigations to confirm our findings are needed.

Vaccination against seasonal flu in childhood and adolescence. Recommendations of the Advisory Committee on Vaccines and Immunizations of the Spanish Association of Pediatrics (CAV-AEP) for the 2024-2025 season.

The flu is a constant threat that can sometimes cause severe forms of disease. The highest incidence rates by age group occur in children under 15 years of age, especially in those under 5 years, in whom the rate of hospitalization is also similar to the population aged 65 years and older. In addition, children are the main transmitters of the infection. In Spain, 5 influenza vaccines are authorized for the paediatric age group: three inactivated tetravalent vaccines harvested from fertilised eggs, one tetravalent inactivated vaccine obtained from cell cultures and one attenuated tetravalent vaccine for intranasal administration, which will become trivalent in the 2024-2025 season by excluding the B Yamagata lineage as recommended by the WHO. The CAV-AEP recommends systematic vaccination in children aged 6-59 months, children and adolescents belonging to risk groups, people who can transmit the flu to groups at risk of complicated flu, and household contacts or close family of infants under 6 months. From 2 years of age, the intranasal attenuated vaccine is preferred due to its greater acceptability and thus contribution to greater vaccination coverage. The CAV-AEP also considers that vaccination against influenza of healthy children and adolescents aged 5-18 years is advisable, as it provides individual protection and promotes protection at the family and community levels. It is especially important to vaccinate all health care professionals against influenza as well as pregnant women at any time during pregnancy.

Enhanced Safety Surveillance of GSK's Inactivated Quadrivalent Seasonal Influenza Vaccine in Belgium, Germany, and Spain During the 2022/2023 Influenza Season.

BACKGROUND: Seasonal influenza is prevented through annual vaccination, especially in children and older adults. These vaccines are annually updated based on World Health Organization recommendations and require continuous safety monitoring. OBJECTIVE: We assessed the frequency and severity of adverse events within 7 days of administering GSK's inactivated quadrivalent seasonal influenza vaccine (IIV4) in Belgium, Germany, and Spain during the 2022/2023 influenza season. METHODS: In this enhanced safety surveillance study, adults who received GSK's IIV4 and parents/guardians/legally acceptable representatives of vaccinated children (aged 6 months-17 years) were invited to complete adverse drug reaction cards reporting adverse events within 7 days post-vaccination. RESULTS: In total, 1332 participants (53.6% female) received at least one dose of GSK's IIV4, including 43 children who received two doses. Overall, 97.8% of adverse drug reaction cards were completed and returned in the study. All participants in Belgium were adults, while 54.7% and 7.4% in Spain and Germany, respectively, were pediatric participants aged 6 months-17 years. After Dose 1, across all age groups, 49.8% of participants reported at least one adverse event. The most common adverse events (cumulative frequency >5%) following Dose 1 were injection-site pain (37.6%), fatigue (15.0%), headache (13.2%), injection-site swelling (9.3%), myalgia (7.6%), and injection-site erythema (7.4%). Across all countries, adverse events were most common in adults aged 18-65 years (59.7%), followed by those aged 3-17 years (47.0%), >65 years (35.7%), and 6-35 months (23.5%). After Dose 2, 18.6% of participants reported at least one adverse event, with general disorders and administration site conditions again being the most frequent. CONCLUSIONS: Across all age and risk groups for serious disease, no serious adverse events related to GSK's IIV4 were reported within 7 days post-vaccination. This study supports and confirms the acceptable safety profile of GSK's IIV4 across all recommended age groups. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number: not applicable.

Molecular epidemiology of pneumococcal carriage in children from Seville, following implementation of the PCV13 immunization program in Andalusia, Spain.

INTRODUCTION: The 13-valent pneumococcal conjugate vaccine (PCV13) universal vaccination programme was introduced in December 2016 in Andalusia. METHODS: A cross-sectional study was conducted on the molecular epidemiology of pneumococcal nasopharyngeal colonization. A total of 397 healthy children were recruited from primary healthcare centres in Seville for the periods 1/4/2018 to 28/2/2020 and 1/11/2021 to 28/2/2022 (PCV13 period). Data from a previous carriage study conducted among healthy and sick children from 1/01/2006 to 30/06/2008 (PCV7 period), were used for comparison of serotype/genotype distributions and antibiotic resistance rates. RESULTS: Overall, 76 (19%) children were colonized with S. pneumoniae during the PCV13 period and there were information available from 154 isolates collected during the PCV7 period. Colonization with PCV13 serotypes declined significantly in the PCV13 period compared with historical controls (11% vs 38%, p = 0.0001), being serotypes 19F (8%), 3 (1%) and 6B (1%) the only circulating vaccine types. Serotypes 15B/C and 11A were the most frequently identified non-PCV13 serotypes during the PCV13 period (14% and 11%, respectively); the later one increased significantly between time periods (p = 0.04). Serotype 11A was exclusively associated in the PCV13 period with ampicillin-resistant variants of the Spain9V-ST156 clone (ST6521 and genetically related ST14698), not detected in the preceding period. CONCLUSIONS: There was a residual circulation of vaccine types following PCV13 introduction, apart from serotype 19F. Serotype 11A increased between PCV13 and PCV7 periods due to emergence and clonal expansion of ampicillin-resistant genotype ST6521.

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.

Penta- and hexavalent vaccination of extremely and very-to-moderate preterm infants born at less than 34 weeks and/or under 1500 g: A systematic literature review.

Debate regarding vaccinating high-risk infants with penta- and hexavalent vaccines persists, despite their good immunogenicity and acceptable safety profile in healthy full-term infants. We report the findings of a systematic literature search that aimed to present data on the immunogenicity, efficacy, effectiveness, safety, impact, compliance and completion of penta- and hexavalent vaccination in high-risk infants, including premature newborns. Data from the 14 studies included in the review showed that the immunogenicity and the safety profile of penta- and hexavalent vaccines in preterm infants was generally similar to those seen in full-term infants, with the exception of an increase in cardiorespiratory adverse events such as apnea, bradycardia and desaturation following vaccination in preterm infants. Despite recommendations of vaccinating preterm infants according to their actual age, and the relatively high completion rate of the primary immunization schedule, vaccination was often delayed, increasing the vulnerability of this high-risk population to vaccine-preventable diseases.

Combined vaccines such as penta- and hexavalent vaccines against multiple childhood diseases are widely used in healthy babies born at term. However, it is still debated whether these vaccines act the same way in babies considered to be high-risk: babies born prematurely at <34 weeks of pregnancy, those with a birthweight of <1500 g or babies with chronic diseases. We did a systematic literature search to find studies on such high-risk babies vaccinated with penta- or hexavalent vaccines; we focused on their antibody levels following vaccination, side effects, and protection from the diseases against which they were vaccinated. We also analyzed whether they were vaccinated on time and with all the doses recommended for healthy full-term babies. We found 14 studies that included premature babies. The results of these studies suggest that premature babies' immune systems respond to penta- and hexavalent vaccines in largely the same way as those of full-term babies; side effects of penta- and hexavalent vaccines are also mostly similar to those seen in full-term babies. However, side effects like pauses in breathing, slow heart rate or low blood oxygen levels seem to be more common in preterm babies; for safety, these babies should be monitored closely after vaccination. Preterm babies are often vaccinated with a delay compared to the recommended schedule. No studies reported data on protection from the diseases covered by penta- and hexavalent vaccinations in preterm babies. More research is needed on penta- and hexavalent vaccination of other high-risk babies besides those born prematurely.

Factors influencing HPV knowledge and vaccine acceptability in parents of adolescent children: results from a survey-based study (KAPPAS study).

Human Papillomavirus (HPV) is one of the most common sexually transmitted infections associated with a wide range of diseases and cancers that may affect both genders. Since 2007, the Spanish National Immunization Program includes HPV vaccination, and currently it only targets 12-year-old girls. The objective of our study is to assess differences in the knowledge of HPV and HPV vaccine acceptability according to different factors, and to identify the role of different sources of information. A cross-sectional, multicenter survey research was carried out in twenty-four pediatric offices in Spain, and included parents of children aged 9 to 14 years old. 1,405 valid survey-responses were considered for the analysis. Parental awareness of HPV and HPV vaccine, as well as vaccine acceptability, are still strongly associated with child gender (girls) and age (12-14 years old). HPV knowledge and HPV vaccine acceptability are related to parental gender, HPV vaccination status and having at least one daughter. Parents who consulted a healthcare source to obtain further information about HPV had greater HPV and HPV vaccine knowledge and acceptability. HPV and HPV vaccine awareness and acceptability are strongly associated with child gender and age, which correlates with the current immunization program.

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.

HPV knowledge and vaccine acceptability: a survey-based study among parents of adolescents (KAPPAS study).

BACKGROUND: Human papillomavirus (HPV) infection is recognized as one of the major causes of infection-related cancer worldwide. In Spain, the HPV vaccination program started in 2007 and until 2022, it targeted 12-year-old girls. METHODS: This was a cross-sectional, multicenter survey-based research carried out at 24 pediatric offices to describe HPV knowledge and vaccine acceptability in parents of children aged between 9 and 14 years-old in Spain. Parents were randomly selected from the medical records following specific quotas to ensure representativeness. The survey included five sections that aim to collect information about sociodemographic characteristics, knowledge of HPV, knowledge and acceptability of vaccines in general, HPV vaccination knowledge and HPV vaccine acceptability. Each section was constituted by a number of close questions with different answer options. Specific scores were assigned to each possible answer to these questions. Based on these scores, four composite variables were created to assess HPV knowledge, HPV vaccine knowledge, HPV vaccine acceptability and vaccines knowledge and acceptability in general. A latent class analysis was performed to identify different group of respondents according to their HPV vaccine acceptability. RESULTS: A total of 1405 valid surveys were included, with 86.19% of the respondents being mothers. The mean score of HPV knowledge was 28.92 out of 40 (maximum value) (95% CI 28.70-29.20) and the mean score of HPV vaccine acceptability was 3.37 out of 5 (maximum value). One third of parents still need more information to take a final decision about HPV vaccination in their children. Parents perceived that females were more likely to become infected than males and tended to associate HPV infection mainly with cervical cancer, showing a. a lack of information about other HPV-related diseases affecting males. CONCLUSIONS: This study results highlight the need for future actions and educational initiatives to raise awareness of HPV consequences in both genders and to contribute to achieving the elimination of HPV-related diseases beyond cervical cancer.

Immunological non-inferiority of a new fully liquid presentation of the MenACWY-CRM vaccine to the licensed vaccine: results from a randomized, controlled, observer-blind study in adolescents and young adults.

A fully liquid MenACWY-CRM vaccine presentation has been developed, modifying the meningococcal serogroup A (MenA) component from lyophilized to liquid. The safety and immunogenicity of the liquid presentation at the end of the intended shelf-life (aged for 24 or 30 months) were compared to the licensed lyophilized/liquid presentation. This multicenter, randomized (1:1), observer-blind, phase 2b study (NCT03433482) enrolled adolescents and young adults (age 10-40 years). In part 1, 844 participants received one dose of liquid presentation stored for approximately 24 months or licensed presentation. In part 2, 846 participants received one dose of liquid presentation stored for approximately 30 months or licensed presentation. After storage, the MenA free saccharide (FS) level was approximately 25% and O-acetylation was approximately 45%. The primary objective was to demonstrate non-inferiority of the liquid presentation to licensed presentation, as measured by human serum bactericidal assay (hSBA) geometric mean titers (GMTs) against MenA, 1-month post-vaccination. Immune responses against each vaccine serogroup were similar between groups. Between-group ratios of hSBA GMTs for MenA were 1.21 (part 1) and 1.11 (part 2), with two-sided 95% confidence interval lower limits (0.94 and 0.87, respectively) greater than the prespecified non-inferiority margin (0.5), thus meeting the primary study objective. No safety concerns were identified. Despite reduced O-acetylation of MenA and increased FS content, serogroup-specific immune responses induced by the fully liquid presentation were similar to those induced by the licensed MenACWY-CRM vaccine, with non-inferior anti-MenA responses. The safety profiles of the vaccine presentations were similar.

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.

Impact of maternal diphtheria-tetanus-acellular pertussis vaccination on pertussis booster immune responses in toddlers: Follow-up of a randomized trial.

BACKGROUND: Transplacentally transferred antibodies induced by maternal pertussis vaccination interfere with infant immune responses to pertussis primary vaccination. We evaluated whether this interference remains in toddlers after booster vaccination. METHODS: In a prior phase IV, observer-blind, placebo-controlled, randomized study (NCT02377349), pregnant women in Australia, Canada and Europe received intramuscular tetanus-reduced-antigen-content diphtheria-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) at 270/7-366/7 weeks' gestation, with crossover immunization postpartum. Their infants were primed (study NCT02422264) and boosted (at 11-18 months; current study NCT02853929) with diphtheria-tetanus-three-component acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenzae type b vaccine (DTaP-HepB-IPV/Hib) and 13-valent pneumococcal conjugate vaccine. Immunogenicity before and after booster vaccination, and reactogenicity and safety of the booster were evaluated descriptively. RESULTS: 263 (Tdap group) and 277 (control group) toddlers received a DTaP-HepB-IPV/Hib booster. Pre-booster vaccination, observed geometric mean concentrations (GMCs) for the three pertussis antigens and diphtheria were 1.4-1.5-fold higher in controls than in the Tdap group. No differences were observed for the other DTaP-HepB-IPV/Hib antigens. One month post-booster vaccination, booster response rates for pertussis antigens were ≥ 92.1% and seroprotection rates for the other DTaP-HepB-IPV/Hib antigens were ≥ 99.2% in both groups (primary objective). Higher post-booster GMCs were observed in controls versus the Tdap group for anti-filamentous hemagglutinin (1.2-fold), anti-pertussis toxoid (1.5-fold) and anti-diphtheria (1.4-fold). GMCs for the other DTaP-HepB-IPV/Hib antigens were similar between groups. Serious adverse events were reported for three toddlers (controls, not vaccination-related). One death occurred pre-booster (Tdap group, not vaccination-related). CONCLUSIONS: As a consequence of interference of maternal pertussis antibodies with infant immune responses to pertussis primary vaccination, pertussis antibody concentrations were still lower in toddlers from Tdap-vaccinated mothers before DTaP-HepB-IPV/Hib booster vaccination. After the booster, antibody concentrations were lower for filamentous hemagglutinin and pertussis toxoid but not for pertactin. The clinical significance of this interference requires further evaluation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02853929.

Correction to: HPV knowledge and vaccine acceptance among European adolescents and their parents: a systematic literature review.

[This corrects the article DOI: 10.1186/s40985-020-00126-5.].

HPV knowledge and vaccine acceptance among European adolescents and their parents: a systematic literature review.

BACKGROUND: Since the introduction of HPV vaccines, several studies have been conducted in different countries to assess HPV knowledge and vaccine acceptance. The aim of this study was to perform a systematic literature review to summarize results and identify factors associated with HPV knowledge and vaccine acceptance in adolescents and their parents and to compile the measurement tools used in the published research studies performed in European countries where HPV is licensed. METHODS: A systematic literature review was conducted for studies published between January 1st 2006 and December 31st 2017. RESULTS: Seventy non-interventional studies performed in 16 European countries met the inclusion criteria. Thirty-eight of them reported data on HPV knowledge and 40 reported data on HPV vaccine acceptance. Further, 51.8% of adolescents (range 0% to 98.6%) and 64.4% of parents (range 1.7% to 99.3%) knew about HPV infection. Insufficient information and safety concerns were the main barriers to vaccination acceptance. CONCLUSION: HPV knowledge and vaccine acceptance are still modest and vary widely between studies across EU countries. Coordinated efforts should be made to provide the relevant population with information for informed decision-making about HPV vaccination.

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.

Prevention of vaccine-matched and mismatched influenza in children aged 6-35 months: a multinational randomised trial across five influenza seasons.

BACKGROUND: Despite the importance of vaccinating children younger than 5 years, few studies evaluating vaccine prevention of influenza have been reported in this age group. We evaluated efficacy of an inactivated quadrivalent influenza vaccine (IIV4) in children aged 6-35 months. METHODS: In this phase 3, observer-blinded, multinational trial, healthy children from 13 countries in Europe, Central America, and Asia were recruited in five independent cohorts, each in a different influenza season. Participants were randomly assigned (1:1) to either IIV4 (15 µg haemagglutinin antigen per strain per 0·5 mL dose; a single dose on day 0 for vaccine-primed children, and two doses, on days 0 and 28, for vaccine-unprimed children) or to one or two doses of a non-influenza control vaccine. Primary endpoints were moderate-to-severe influenza or all influenza (irrespective of disease severity) confirmed by RT-PCR on nasal swabs. Cultured isolates were further characterised as antigenically matched or mismatched to vaccine strains. Efficacy was assessed in the per-protocol cohort and total vaccinated cohort (time-to-event analysis), and safety was assessed in the total vaccinated cohort. FINDINGS: Between Oct 1, 2011, and Dec 31, 2014, 12 018 children were recruited into the total vaccinated cohort (6006 children in the IIV4 group and 6012 children in the control group). 356 (6%) children in the IIV4 group and 693 (12%) children in the control group had at least one case of RT-PCR-confirmed influenza. Of these 1049 influenza strains, 138 (13%) were A/H1N1, 529 (50%) were A/H3N2, 69 (7%) were B/Victoria, and 316 (30%) were B/Yamagata. Overall, 539 (64%) of 848 antigenically characterised isolates were vaccine-mismatched (16 [15%] of 105 for A/H1N1; 368 [97%] of 378 for A/H3N2; 54 [86%] of 63 for B/Victoria; 101 [33%] of 302 for B/Yamagata). Vaccine efficacy was 63% (97·5% CI 52-72) against moderate-to-severe influenza and 50% (42-57) against all influenza in the per-protocol cohort, and 64% (53-73) against moderate-to-severe influenza and 50% (42-57) against all influenza in the total vaccinated cohort. There were no clinically meaningful safety differences between IIV4 and control. INTERPRETATION: IIV4 prevented influenza A and B in children aged 6-35 months despite high levels of vaccine mismatch. Vaccine efficacy was highest against moderate-to-severe disease, which is the most clinically important endpoint associated with greatest burden. FUNDING: GlaxoSmithKline Biologicals SA.