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PURPOSE: Many countries recommend human papillomavirus (HPV) vaccination in female adolescents at an age when other vaccines are routinely administered. This open, randomized, multicenter study (108464/NCT00426361) evaluated coadministration of HPV-16/18 AS04-adjuvanted vaccine with diphtheria-tetanus-acellular pertussis-inactivated poliovirus vaccine (dTpa-IPV). METHODS: Healthy females aged 10-18 years were randomized to receive HPV vaccine at months 0, 1, and 6 (n = 248), HPV vaccine coadministered with dTpa-IPV at month 0 and HPV vaccine at months 1 and 6 (n = 255), or dTpa-IPV at month 0 followed by HPV vaccine at months 1, 2, and 7 (n = 248). Immunogenicity was evaluated at months 0, 1, and 7 or 8 (depending on group). Vaccine reactogenicity and safety were also assessed. RESULTS: Coadministered dTpa-IPV and HPV vaccine was noninferior to dTpa-IPV alone in terms of seroprotection against diphtheria (99.2% and 100%), tetanus (100% and 100%) and poliovirus types 1, 2, and 3 (> or = 99.6%), and geometric mean antibody concentrations (ELISA Units/mL) for pertussis toxoid (84 vs. 75), filamentous hemagglutinin (612 and 615) and pertactin (426 and 360) at month 1. Coadministered dTpa-IPV and HPV vaccine was noninferior to HPV vaccine alone in terms of seroconversion rates for HPV-16 (99.5% and 100%) and HPV-18 (99.5% and 100%) and geometric mean antibody titers (ELISA Units/mL) for HPV-16 (15,608 and 18,965) and HPV-18 (6,597 and 6,902) at month 7. Coadministration was generally well tolerated. The reactogenicity of dTpa-IPV and the first dose of HPV vaccine was similar. CONCLUSIONS: Results from this study support coadministration of the HPV-16/18 AS04-adjuvanted vaccine with dTpa-IPV vaccine in females aged 10-18 years. [ABSTRACT FROM AUTHOR]

Persistent infection with human papillomavirus (HPV) is a necessary cause of cervical cancer, resulting annually in 274,000 deaths worldwide. Two prophylactic HPV vaccines are licensed in >100 countries, and immunization programs in young, adolescent girls have been widely implemented. HPV-16/18 AS04-adjuvanted vaccine (Cervarix; GlaxoSmithKline Biologicals, Rixensart, Belgium) has demonstrated type-specific protection against the five most frequent cancer-causing types (16, 18, 31, 33, and 45) that are responsible for 82% of invasive cervical cancers globally. Cervarix has demonstrated efficacy against HPV-45, which is the third most common HPV type in cervical cancer and adenocarcinoma. Final results of a large phase 3 trial recently showed Cervarix substantially reduced the overall burden of cervical precancerous lesions (cervical intraepithelial neoplasia 2+) by 70.2% in an HPV-naïve population approximating young girls prior to sexual debut, the target of most current vaccination programs. Protection offered by Cervarix against nonvaccine types (mainly 31, 33, and 45) might potentially allow for 11%-16% additional protection against cervical cancers, compared to a vaccine only offering protection against HPV-16/18. Another recent study directly compared the antibody response of Cervarix to that of quadrivalent HPV-6/11/16/18 vaccine (Gardasil; Merck, Whitehouse Station, NJ, USA). Cervarix induced significantly superior neutralizing antibody levels as compared with Gardasil for HPV-16 and HPV-18 in all age groups studied. This may translate into more women having detectable (neutralizing) antibodies in cervicovaginal secretions for HPV-16 and HPV-18 after vaccination with Cervarix when compared with Gardasil. Cervarix induced significantly higher frequencies of antigen-specific memory B-cells and T-cells in responders for HPV-16 and HPV-18 as compared with Gardasil. Cervarix continues to show sustained high levels of total and neutralizing antibodies for HPV-16 and HPV-18, 7.3 years after vaccination. This is associated with high efficacy and no breakthrough cases in the HPV-naïve population, and is the longest duration follow-up for safety, immunogenicity, and efficacy for any licensed HPV vaccine to date. [ABSTRACT FROM AUTHOR]

BACKGROUND: We evaluated the efficacy of the human papillomavirus HPV-16/18 AS04-adjuvanted vaccine against non-vaccine oncogenic HPV types in the end-of-study analysis after 4 years of follow-up in PATRICIA (PApilloma TRIal against Cancer In young Adults). METHODS: Healthy women aged 15-25 years with no more than six lifetime sexual partners were included in PATRICIA irrespective of their baseline HPV DNA status, HPV-16 or HPV-18 serostatus, or cytology. Women were randomly assigned (1:1) to HPV-16/18 vaccine or a control hepatitis A vaccine, via an internet-based central randomisation system using a minimisation algorithm to account for age ranges and study sites. The study was double-blind. The primary endpoint of PATRICIA has been reported previously; the present analysis evaluates cross-protective vaccine efficacy against non-vaccine oncogenic HPV types in the end-of-study analysis. Analyses were done for three cohorts: the according-to-protocol cohort for efficacy (ATP-E; vaccine n=8067, control n=8047), total vaccinated HPV-naive cohort (TVC-naive; no evidence of infection with 14 oncogenic HPV types at baseline, approximating young adolescents before sexual debut; vaccine n=5824, control n=5820), and the total vaccinated cohort (TVC; all women who received at least one vaccine dose, approximating catch-up populations that include sexually active women; vaccine n=9319, control=9325). Vaccine efficacy was evaluated against 6-month persistent infection, cervical intraepithelial neoplasia grade 2 or greater (CIN2+) associated with 12 non-vaccine HPV types (individually or as composite endpoints), and CIN3+ associated with the composite of 12 non-vaccine HPV types. This study is registered with ClinicalTrials.gov, number NCT00122681. FINDINGS: Consistent vaccine efficacy against persistent infection and CIN2+ (with or without HPV-16/18 co-infection) was seen across cohorts for HPV-33, HPV-31, HPV-45, and HPV-51. In the most conservative analysis of vaccine efficacy against CIN2+, where all cases co-infected with HPV-16/18 were removed, vaccine efficacy was noted for HPV-33 in all cohorts, and for HPV-31 in the ATP-E and TVC-naive. Vaccine efficacy against CIN2+ associated with the composite of 12 non-vaccine HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68), with or without HPV-16/18 co-infection, was 46·8% (95% CI 30·7-59·4) in the ATP-E, 56·2% (37·2-69·9) in the TVC-naive, and 34·2% (20·4-45·8) in the TVC. Corresponding values for CIN3+ were 73·8% (48·3-87·9), 91·4% (65·0-99·0), and 47·5% (22·8-64·8). INTERPRETATION: Data from the end-of-study analysis of PATRICIA show cross-protective efficacy of the HPV-16/18 vaccine against four oncogenic non-vaccine HPV types-HPV-33, HPV-31, HPV-45, and HPV-51-in different trial cohorts representing diverse groups of women. FUNDING: GlaxoSmithKline Biologicals. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cervical intraepithelial neoplasia grade 2 or greater (CIN2+) is the surrogate endpoint used in licensure trials of human papillomavirus (HPV) vaccines. Vaccine efficacy against CIN3+, the immediate precursor to invasive cervical cancer, is more difficult to measure because of its lower incidence, but provides the most stringent evidence of potential cancer prevention. We report vaccine efficacy against CIN3+ and adenocarcinoma in situ (AIS) in the end-of-study analysis of PATRICIA (PApilloma TRIal against Cancer In young Adults). METHODS: Healthy women aged 15-25 years with no more than six lifetime sexual partners were included in PATRICIA, irrespective of their baseline HPV DNA status, HPV-16 or HPV-18 serostatus, or cytology. Women were randomly assigned (1:1) to receive an HPV-16/18 AS04-adjuvanted vaccine or a control hepatitis A vaccine via an internet-based central randomisation system using a minimisation algorithm to account for age ranges and study sites. The patients and study investigators were masked to allocated vaccine. The primary endpoint of PATRICIA has been reported previously. In the present end-of-study analysis, we focus on CIN3+ and AIS in the populations of most clinical interest, the total vaccinated cohort (TVC) and the TVC-naive. The TVC comprised all women who received at least one vaccine dose, approximating catch-up populations and including sexually active women (vaccine n=9319; control=9325). The TVC-naive comprised women with no evidence of oncogenic HPV infection at baseline, approximating early adolescent HPV exposure (vaccine n=5824; control=5820). This study is registered with ClinicalTrials.gov, number NCT00122681. FINDINGS: Vaccine efficacy against CIN3+ associated with HPV-16/18 was 100% (95% CI 85·5-100) in the TVC-naive and 45·7% (22·9-62·2) in the TVC. Vaccine efficacy against all CIN3+ (irrespective of HPV type in the lesion and including lesions with no HPV DNA detected) was 93·2% (78·9-98·7) in the TVC-naive and 45·6% (28·8-58·7) in the TVC. In the TVC-naive, vaccine efficacy against all CIN3+ was higher than 90% in all age groups. In the TVC, vaccine efficacy against all CIN3+ and CIN3+ associated with HPV-16/18 was highest in the 15-17 year age group and progressively decreased in the 18-20 year and 21-25 year age groups. Vaccine efficacy against all AIS was 100% (31·0-100) and 76·9% (16·0-95·8) in the TVC-naive and TVC, respectively. Serious adverse events occurred in 835 (9·0%) and 829 (8·9%) women in the vaccine and control groups, respectively; only ten events (0·1%) and five events (0·1%), respectively, were considered to be related to vaccination. INTERPRETATION: PATRICIA end-of-study results show excellent vaccine efficacy against CIN3+ and AIS irrespective of HPV DNA in the lesion. Population-based vaccination that incorporates the HPV-16/18 vaccine and high coverage of early adolescents might have the potential to substantially reduce the incidence of cervical cancer. FUNDING: GlaxoSmithKline Biologicals. [ABSTRACT FROM AUTHOR]

Background: The adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) is approved in adults aged ≥60 years. We evaluated RSVPreF3 OA immunogenicity and safety in adults aged 50-59 years without or with increased risk for RSV disease due to specific chronic medical conditions., Methods: This observer-blind, phase 3, noninferiority trial included adults aged 50-59 years, stratified into 2 subcohorts: those with and those without predefined, stable, chronic medical conditions leading to an increased risk for RSV disease. Participants in both subcohorts were randomized 2:1 to receive RSVPreF3 OA or placebo. A control group of adults aged ≥60 years received RSVPreF3 OA. Primary outcomes were RSV-A and RSV-B neutralization titers (geometric mean titer ratios and sero-response rate differences) 1 month post-vaccination in 50-59-year-olds versus ≥60-year-olds. Cell-mediated immunity and safety were also assessed., Results: The exposed population included 1152 participants aged 50-59 years and 381 participants aged ≥60 years. RSVPreF3 OA was immunologically noninferior in 50-59-year-olds versus ≥60-year-olds; noninferiority criteria were met for RSV-A and RSV-B neutralization titers in those with and those without increased risk for RSV disease. Frequencies of RSVPreF3-specific polyfunctional CD4+ T cells increased substantially from pre- to 1 month post-vaccination. Most solicited adverse events had mild-to-moderate intensity and were transient. Unsolicited and serious adverse event rates were similar in all groups., Conclusions: RSVPreF3 OA was immunologically noninferior in 50-59-year-olds compared to ≥60-year-olds, in whom efficacy was previously demonstrated. The safety profile in 50-59-year-olds was consistent with that in ≥60-year-olds., Clinical Trial Registration: ClinicalTrials.gov: NCT05590403., Competing Interests: Potential conflicts of interest . H. A. H., M. d. H., B. S., S. D., M.-P. D., D. D., J. H., C. V., and V. H. are/were GSK employees at the time when the study was designed and/or conducted. H. A. H., M. d. H., B. S., S. D., M.-P. D., D. D., J. H., and V. H. hold shares in GSK as part of their employee remuneration. M.-P. D. is a co-applicant on a pending patent filed by GSK. M. F. received study-related payments for training and study conduct from GSK. T. F. S. received honoraria for lectures from AstraZeneca, Bavarian Nordic, Biogen, CSL-Seqirus, GSK, Janssen-Cilag, Merck-Serono, Moderna, Novavax, MSD, Pfizer, Roche, Sanofi-Aventis, and Takeda; he participated on advisory boards for Bavarian Nordic, CSL-Seqirus, BioNTech, GSK, Moderna, Novavax, and Takeda. S. A. N. declares study-related payments to his institution from GSK and support from GSK to attend investigators meetings. J. R.-G. declares study-related payments from GSK and honoraria and support for attending meetings and/or travel from GSK, Pfizer, and Sanofi-MSD; he also participated on data and safety monitoring boards or advisory boards from GSK and Pfizer. C. Z. received grants from GSK for the conduct of this study and support from GSK for attending meetings. J. G. declares study-related payments from GSK; grants from Novartis, Pharmalog, New Amsterdam Pharma, Syneos, Winecker Pharma, and Lilly; and consulting fees, honoraria, payment for expert testimony, and support for attending meetings and/or travel from GSK. C. V.-P. is a former employee of QPS Netherlands B.V. The other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The recently approved AS01E-adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine for older adults (RSVPreF3 OA) demonstrated high efficacy against RSV-related disease in ≥60-year-olds., Methods: This ongoing phase 3 study in ≥60-year-olds evaluates immune persistence until 3 years after RSVPreF3 OA vaccination. Here, we describe interim results on humoral and cell-mediated immunogenicity, reactogenicity, and safety until 1 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) vs 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 1 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; 1 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 1 year. The vaccine was well tolerated with an acceptable safety profile. Clinical Trials Registration. NCT04732871 (ClinicalTrials.gov)., Competing Interests: Potential conflicts of interest. T. F. S. reports having received payment or honoraria for lecturing or advisory boards from GSK, AstraZeneca, Bavarian Nordic, Biogen, BioNTech, Janssen-Cilag, Merck-Serono, Moderna, MSD, Pfizer, Roche, Sanofi-Aventis, Seqirus, Takeda, and for conducting clinical vaccine trials from GSK, Pfizer, and Serum Institute of India. S.-J. H. received research support and consultation fees from GSK. P. Y. assisted as Site Principal Investigator for the current study. C. P. A. was a paid Site Principal Investigator for the study and has received consulting fees from Merck and Boehringer Ingelheim. D. C., M. d. H., N. D. S., B. S., A. L., C. M., A. O., P. N., M. L., and V. H. were employees of GSK at the time the study was designed, initiated, and/or conducted. D. C., M. d. H., N. D. S., B. S., C.M., A. O., M. L., and V. H. hold shares of stock in the company as part of their employee remuneration. A. O. is a co-applicant on a pending patent filed by GSK. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD) in ≥60-years-olds over 1 RSV season. We evaluated efficacy and safety of 1 RSVPreF3 OA dose and of 2 RSVPreF3 OA doses given 1 year apart against RSV-LRTD over 2 RSV seasons post-dose 1., Methods: In this phase 3, blinded trial, ≥60-year-olds were randomized (1:1) to receive RSVPreF3 OA or placebo pre-season 1. RSVPreF3 OA recipients were re-randomized (1:1) to receive a second RSVPreF3 OA dose (RSV_revaccination group) or placebo (RSV_1dose group) pre-season 2; participants who received placebo pre-season 1 received placebo pre-season 2 (placebo group). Efficacy of both vaccine regimens against RSV-LRTD was evaluated over 2 seasons combined (confirmatory secondary objective, success criterion: lower limits of 2-sided CIs around efficacy estimates >20%)., Results: The efficacy analysis comprised 24 967 participants (RSV_1dose: 6227; RSV_revaccination: 6242; placebo: 12 498). Median efficacy follow-up was 17.8 months. Efficacy over 2 seasons of 1 RSVPreF3 OA dose was 67.2% (97.5% CI: 48.2-80.0%) against RSV-LRTD and 78.8% (95% CI: 52.6-92.0%) against severe RSV-LRTD. Efficacy over 2 seasons of a first dose followed by revaccination was 67.1% (97.5% CI: 48.1-80.0%) against RSV-LRTD and 78.8% (95% CI: 52.5-92.0%) against severe RSV-LRTD. Reactogenicity/safety of the revaccination dose were similar to dose 1., Conclusions: One RSVPreF3 OA dose was efficacious against RSV-LRTD over 2 RSV seasons in ≥60-year-olds. Revaccination 1 year post-dose 1 was well tolerated but did not seem to provide additional efficacy benefit in the overall study population., Clinical Trials Registration: ClinicalTrials.gov: NCT04886596., Competing Interests: Potential conflicts of interest . M. G. I. declares that research support from GSK was paid to his previous institution, Northwestern University; he received consulting fees from Adagio Therapeutics, ADMA Biologics, Adamis Pharmaceuticals, AlloVir, Atea, Cidara Therapeutics, Genentech/Roche, Janssen, Shionogi, Takeda, Talaris, and Eurofins Viracor; and payment for participating in data safety monitoring boards or advisory boards from Adamis Pharmaceuticals, AlloVir, National Institutes of Health, CSL Behring, Janssen, Merck, Seqirus, Takeda, and Talaris; all of these ended in December 2022; M. G. I. also receives author royalties from UpToDate, which is ongoing, and serves as Chair of the International Society for Influenza and other Respiratory Virus Diseases Antiviral Group and was Editor-in-Chief of Transplant Infectious Disease. A. P. declares funding from GSK for conducting the trial. A. P. also declares that his institution received grants from Chiesi, AstraZeneca, GSK, Sanofi, and Agenzia Italiana del Farmaco; that he received consulting fees from Chiesi, AstraZeneca, GSK, Novartis, Sanofi, Avillion, and ELPEN Pharmaceuticals; payment for participation in advisory boards from Chiesi, AstraZeneca, GSK, Novartis, Sanofi, IQVIA, Avillion, and ELPEN Pharmaceuticals; and honoraria from Chiesi, AstraZeneca, GSK, Menarini, Novartis, Zambon, Mundipharma, Sanofi, Edmond Pharmaceuticals, IQVIA, Avillion, and ELPEN Pharmaceuticals. R. G. F. declares having received payment from GSK for lectures and support for travel related to these activities. J. M. L. reports grants from GSK paid to her institution for the conduct of the trial and from GSK, Pfizer, Merck, Moderna, Sanofi, Inventprise, and VBI Vaccines for other trials; J. M. L. also reports being a board member of Seqirus and participating on a data safety monitoring board or advisory board for Vaxcyte; she is an expert panelist for Canada's Drug and Health Technology Agency for the review of nirsevimab. I. L.-R. declares that her institution received funding from GSK for conducting this trial; from Icosavax, Virometix, Janssen Vaccines, Curevac, Moderna, Osivax, MSD, ICON Genetics, and OSE Immunotherapeutics for other vaccine trials; from Janssen Vaccines and MSD for consulting services; and from Janssen Vaccines for participation on a data safety monitoring board or advisory board. F. M.-T. declares that his institution received payment from GSK for conducting this trial and from Ablynx, Abbott, Seqirus, Sanofi, MSD, Merck, Pfizer, Roche, Regeneron, Janssen, Medimmune, Novavax, Novartis, and GSK for other vaccine trials; F. M.-T. also reports receiving honoraria for lectures from Sanofi, MSD, Moderna, GSK, Biofabri, AstraZeneca, Novavax, Janssen, and Pfizer; payment of travel expenses and meeting fees from Pfizer, MSD, GSK, and Sanofi; and participation on data safety monitoring boards or advisory boards for Pfizer and Biofabri; F. M.-T. is also a member of the World Health Organization’s (WHO's) European Technical Advisory Group of Experts, coordinator of the Spanish Pediatric Clinical Trials Network, and coordinator of the WHO Collaborating Center for Vaccine Safety of Santiago de Compostela. T. F. S. reports honoraria and/or participation on data safety monitoring boards or advisory boards from Alexion, AstraZeneca, Bavarian Nordic, Biogen, Biontech, GSK, Janssen-Cilag, Merck-Serono, Moderna, MSD, Novavax, Pfizer, Roche, Sanofi-Aventis, Seqirus, Synlab, Takeda, and va-Q-tec. R. N. v. Z.-S. reports that his institution received support from Boehringer Ingelheim for the Interstitial Lung Diseases (ILD) registry and that he received consulting fees from GSK and honoraria for lectures from Glenmark, Boehringer Ingelheim, Cipla, and Novartis; R. N. v. Z.-S. also participated on data safety monitoring boards or advisory boards for OnQ SA; he is president of the South African Thoracic Society and co-chair of the International Health Committee of the American Thoracic Society. C. V., N. D., O. G., L. F., M.-P. D., L. K., V. H., A. O., M. V. d. W., and D. D. are employed by GSK and have stock options or shares from GSK. N. D. is co-applicant on a pending patent for vaccination against RSV and has stock options from Haleon. L. F., M.-P. D., A. O., and M. V. d. W. are co-applicants on a pending patent filed by GSK. The other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Aim: Seasonal influenza poses a significant burden of disease, affecting not only older adults but also individuals under the age of 60. It carries a high economic burden, mainly driven by influenza-associated productivity losses in the working population. Conventional egg-based influenza vaccines may have reduced effectiveness due to antigen adaptation in eggs. In contrast, cell-based influenza vaccines are less likely to be affected by such antigen adaptation. This review aims to present real-world data (RWD) comparing the effectiveness of quadrivalent cell-based (QIVc) and egg-based (QIVe) influenza vaccines over three consecutive seasons., Methods: A comprehensive review was conducted, analyzing RWD from retrospective cohort and case-control studies on the relative vaccine effectiveness (rVE) of QIVc versus QIVe during the 2017/18-2019/20 seasons., Results: This study included six retrospective cohort studies and one case-control study, with a combined total of approximately 29 million participants. A cohort study involving people aged ≥4 years during the 2017/18 season showed a statistically significant rVE of QIVc compared to QIVe in preventing influenza-like illness, with a value of 36.2%. QIVc demonstrated statistically significant superiority over QIVe in preventing outpatient and inpatient medical encounters as observed in two cohort studies conducted during the 2018/19 and 2019/20 seasons. The rVE of QIVc compared to QIVe was found to be 7.6% in individuals aged ≥4 years and 9.5% in individuals aged ≥18 years. Three additional cohort studies conducted between 2017/18-2019/20 reported a statistically significant improvement in rVE (5.3-14.4%) of QIVc compared to QIVe in preventing influenza-related hospitalizations and emergency department visits due to influenza in individuals aged 4-64 years. In a case-control study across all three seasons, QIVc showed statistically significantly higher effectiveness compared to QIVe in preventing test-confirmed influenza, with rVEs of 10.0-14.8%., Conclusions: RWD from the 2017/18-2019/20 seasons demonstrated that QIVc is more effective than QIVe in preventing influenza-related outcomes in individuals aged 4-64 years. Preferential use of cell-based influenza vaccines, as opposed to conventional egg-based vaccines, could reduce the burden of influenza-related symptoms on individuals and alleviate the economic impact on the German population under 60 years of age., Competing Interests: CSL Seqirus GmbH funded the publication.Dr. Dietmar Beier: Advisory Board for CSL Seqirus.Prof. Dr. Barbara C. Gärtner: Advisory Board and honoraria for lectures for CSL Seqirus, Sanofi, GSK, Moderna, BioNTech, Pfizer, Viatris.Dr. Gunther Gosch: Lecturing activities and participation in advisory boards for AstraZeneca, CLS Seqirus, GSK, MSD, Pfizer, Sanofi Aventis. Prof. Dr. Klaus Wahle: Lectures and participation in advisory boards on behalf of or for SPMSD, CSL Seqirus, Pfizer, GSK, BioNTech. Dr. Luise Wendt: -Dr. Laura-Christin Förster is employed by CSL Seqirus GmbH.Kim J. Schmidt is employed by Xcenda GmbH, which received funding from CSL Seqirus GmbH for the preparation of this manuscript.Prof. Dr. Tino F. Schwarz: Honoraria for consulting and lectures for Alexion, AstraZeneca, Bavarian Nordic, Biogen, BioNTech, GSK, Janssen-Cilag, Merck-Serono, Moderna, MSD, Novavax, Pfizer, Roche, Sanofi-Aventis, CSL Seqirus, Synlab, Takeda and va-Q-tec., (Copyright © 2024 Gärtner et al.)

Influenza pandemics pose a serious risk to the global population, with the potential for high morbidity and mortality. An adjuvanted H5N1 vaccine (aH5N1) has been approved for prophylaxis against the avian influenza virus H5N1, which is a likely cause of future pandemics. In this phase-III, stratified, randomized, controlled, observer-blind, multicenter study, we evaluated the safety and immunogenicity of aH5N1 in four separate groups of adults: adults 18-60 years of age who were healthy or had high-risk medical conditions and older adults ≥61 years of age who were healthy or had high-risk medical conditions. Subjects were randomly assigned to aH5N1 or the comparator, adjuvanted trivalent seasonal influenza vaccine (aTIV). Antibody responses to aH5N1 were increased in all four subgroups and, within each age stratum, largely consistent between healthy subjects and those with medical conditions. Injection-site pain was reported by 66-73% of younger and 36-42% of older-aH5N1 recipients, and fatigue and myalgia were reported by 22-41% of subjects across age and health subgroups. No serious adverse events or deaths were considered related to the study vaccine. In conclusion, aH5N1 increased antibody responses regardless of age or health status and demonstrated a clinically acceptable safety and tolerability profile.

Background: Respiratory syncytial virus (RSV) is a contagious pathogen causing acute respiratory infections (ARIs). Symptoms range from mild upper respiratory tract infections to potentially life-threatening lower respiratory tract disease (LRTD). In adults ≥60 years old, vaccine efficacy of a candidate vaccine for older adults (RSVPreF3 OA) was 71.7% against RSV-ARI and 82.6% against RSV-LRTD (AReSVi-006/NCT04886596). We present the patient-reported outcomes (PROs) from the same trial at the end of the first RSV season in the northern hemisphere (April 2022)., Methods: In this phase 3 trial, adults aged ≥60 years were randomized (1:1) to receive one dose of RSVPreF3 OA vaccine or placebo. PROs were assessed using InFLUenza Patient-Reported Outcome (FLU-PRO), Short Form-12 (SF-12), and EuroQol-5 Dimension (EQ-5D) questionnaires. Peak FLU-PRO Chest/Respiratory scores during the first 7 days from ARI episode onset were compared using a Wilcoxon test. Least squares mean (LSMean) of SF-12 physical functioning (PF) and EQ-5D health utility scores were estimated using mixed effects models., Results: In the RSVPreF3 OA group ( N  = 12,466), 27 first RSV-ARI episodes were observed versus 95 in the Placebo group ( N  = 12,494). Median peak FLU-PRO Chest/Respiratory scores were lower in RSVPreF3 OA (1.07) versus Placebo group (1.86); p  = 0.0258. LSMean group differences for the PF and EQ-5D health utility score were 7.00 (95% confidence interval [CI]: -9.86, 23.85; p  = 0.4125) and 0.0786 (95% CI: -0.0340, 0.1913; p  = 0.1695)., Conclusions: The RSVPreF3 OA vaccine, in addition to preventing infection, attenuated the severity of RSV-associated symptoms in breakthrough infections, with trends of reduced impact on PF and health utility., Competing Interests: During this study, Eliazar Sabater Cabrera, Desmond Curran, Veronica Hulstrøm, Lusine Kostanyan, and Daniel Molnar were GSK employees. Eliazar Sabater Cabrera, Desmond Curran, Veronica Hulstrøm, Lusine Kostanyan, and Daniel Molnar hold shares in GSK. Isabel Maria Galan Melendez was an investigator for the study of RSV OA‐006 and declares to have received payments from GSK per contract, as well as equipment on loan and study materials. Silvia Narejos Pérez participated as principal investigator (PI) in clinical trials with different sponsors, including GSK and received financial support during the present manuscript. As a PI, she collaborated in the presentation of the results of clinical trials of vaccines and received financial support for attending meetings and/or travel. Laura Helman received payment for completing the study work and was given financial support for attending meetings and/or travel as an investigator. During the development of the study, John H. Powers III was a consultant for GSK and Vir on the clinical study design. Besides that, he received consulting fees from Adaptive Phage, Arrevus, Atheln, Bavarian Nordic, Cellularity, Eicos, Evofem, Eyecheck, Gilead, Mustang, OPKO, Otsuka, Resolve, Romark, Spine BioPharma, and UTIlity. He is an unpaid board member of Health Literacy Media. Mika Rämet declares that his institute was sponsored by GSK to perform the current study. Tino Schwarz has received honoraria for lecturing or advisory boards from Alexion, AstraZeneca, Bavarian Nordic, Biogen, Biontech, CSL Seqirus, GSK, Janssen‐Cilag, Merck‐Serono, Moderna, MSD, Novavax, Pfizer, Roche, Sanofi‐Aventis, and Takeda and for conducting clinical vaccine trials from GSK, Pfizer, Clover Biopharmaceuticals, and Serum Institute of India. Brigitte Stephan participated as investigator in clinical trials with different sponsors, including GSK. Sean Matthews, Lina Pérez Breva, Nathalie Roy, Dae Won Park, and Axel Schaefer have nothing to declare., (© 2024 GSK. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Seasonal influenza causes a significant burden of disease in the German population and is associated with high societal costs. Persons aged 60 years and older are particularly at risk due to immunosenescence and chronic disease and account for a large proportion of influenza-associated hospitalizations and deaths. Adjuvanted, high-dose, recombinant and cell-based influenza vaccines have been developed to improve the effectiveness compared with conventional vaccines. Recent observational studies show better effectiveness of adjuvanted vaccine over conventional vaccines and similar effectiveness to the high-dose vaccine in older adults. Some countries have already considered the new evidence in their vaccination recommendations for the current or earlier seasons. The availability of the vaccines for older adults should also be ensured in Germany to guarantee a high level of vaccination protection., Competing Interests: Die Durchführung der Publikation wurde finanziell von der Seqirus GmbH unterstützt. Dr. Markus Frühwein: – Vorträge/Beratung: Astra Zeneca, Bavarian, Nordic, Biontech, Janßen, GSK, Moderna, MSD, Pfizer, Sanofi, Seqirus, Takeda, Viatris. Prof. Dr. Jörg Schelling: – Beratungshonorare von AstraZeneca, Bavarian Nordic, der GSK Unternehmensgruppe, Sanofi Pasteur, Pfizer, Johnson & Johnson, MSD, BioNTech, Seqirus, Takeda, Viatris – Zahlungen oder Honorare für Vorlesungen, Präsentationen, Rednerbüros, Manuskripterstellung oder Bildungsveranstaltungen von GSK, Sanofi Pasteur, Pfizer, Johnson & Johnson, MSD, BioNTech, Seqirus, Takeda, Viatris – Unterstützung für die Teilnahme an Sitzungen und/oder Reisen von Sanofi Pasteur und Pfizer und Aktienbesitz von Valneva außerhalb der eingereichten Arbeit. Prof. Dr. Klaus Wahle: – Vortragstätigkeiten und Teilnahme an Advisory Boards im Auftrag bzw. für die Firmen SPMSD, Seqirus, Pfizer, GSK, Biontech. Dr. Dietmar Beier: – Advisory Board für Seqirus. Dr. Anja Kwetkat: – Forschungsunterstützung: Robert-Bosch-Stiftung – Forschungskolleg Geriatrie, Pfizer Pharma GmbH – Beratungs-/Gutachtertätigkeit: Projekt Grippeschutz – Seqirus, Advisory Board Prävention Herpes Zoster – GlaxoSmithKline GmbH & Co. KG, Advisory Board Sektorenübergreifendes Impfmanagement – Pfizer Pharma GmbH, Advisory Board Hochdosis Influenza Impfstoff – Sanofi-Pasteur, Advisory Board COVID-19 Impfstoff AZD1222 – AstraZeneca – Vortragstätigkeit: Pfizer Pharma GmbH, Fa. MSD, Fa. Novartis, Fa. Daiichi-Sankyo, Fa. Bristol-Myers Squibb, Fa. Sanofi-Pasteur – Ehrenämter: Sprecherin der AG Impfen der Deutschen Gesellschaft für Geriatrie e. V. (DGG e. V.), Mitglied DRG-Projektgruppe des Bundesverbandes Geriatrie e. V. (BVG e. V.). Prof. Dr. Tino Schwarz: – Honorare für Beratung und Vorträge: Biogen, Merck-Serono, GSK, Sanofi-Aventis, Pfizer, Seqirus, Synlab, AstraZeneca, Roche, MSD, va-Q-tec, Bavarian Nordic, Janssen-Cilag, Alexion, Takeda, Biontech, MSD, Moderna, (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Respiratory syncytial virus (RSV) is an important cause of acute respiratory infection, lower respiratory tract disease, clinical complications, and death in older adults. There is currently no licensed vaccine against RSV infection., Methods: In an ongoing, international, placebo-controlled, phase 3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive a single dose of an AS01 E -adjuvanted RSV prefusion F protein-based candidate vaccine (RSVPreF3 OA) or placebo before the RSV season. The primary objective was to show vaccine efficacy of one dose of the RSVPreF3 OA vaccine against RSV-related lower respiratory tract disease, confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR), during one RSV season. The criterion for meeting the primary objective was a lower limit of the confidence interval around the efficacy estimate of more than 20%. Efficacy against severe RSV-related lower respiratory tract disease and RSV-related acute respiratory infection was assessed, and analyses according to RSV subtype (A and B) were performed. Safety was evaluated., Results: A total of 24,966 participants received one dose of the RSVPreF3 OA vaccine (12,467 participants) or placebo (12,499). Over a median follow-up of 6.7 months, vaccine efficacy against RT-PCR-confirmed RSV-related lower respiratory tract disease was 82.6% (96.95% confidence interval [CI], 57.9 to 94.1), with 7 cases (1.0 per 1000 participant-years) in the vaccine group and 40 cases (5.8 per 1000 participant-years) in the placebo group. Vaccine efficacy was 94.1% (95% CI, 62.4 to 99.9) against severe RSV-related lower respiratory tract disease (assessed on the basis of clinical signs or by the investigator) and 71.7% (95% CI, 56.2 to 82.3) against RSV-related acute respiratory infection. Vaccine efficacy was similar against the RSV A and B subtypes (for RSV-related lower respiratory tract disease: 84.6% and 80.9%, respectively; for RSV-related acute respiratory infection: 71.9% and 70.6%, respectively). High vaccine efficacy was observed in various age groups and in participants with coexisting conditions. The RSVPreF3 OA vaccine was more reactogenic than placebo, but most adverse events for which reports were solicited were transient, with mild-to-moderate severity. The incidences of serious adverse events and potential immune-mediated diseases were similar in the two groups., Conclusions: A single dose of the RSVPreF3 OA vaccine had an acceptable safety profile and prevented RSV-related acute respiratory infection and lower respiratory tract disease and severe RSV-related lower respiratory tract disease in adults 60 years of age or older, regardless of RSV subtype and the presence of underlying coexisting conditions. (Funded by GlaxoSmithKline Biologicals; AReSVi-006 ClinicalTrials.gov number, NCT04886596.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Respiratory syncytial virus (RSV) causes respiratory tract infections, which may require hospitalization especially in early infancy. Transplacental transfer of RSV antibodies could confer protection to infants in their first months of life., Methods: In this first-in-human, placebo-controlled study, 502 healthy nonpregnant women were randomized 1:1:1:1 to receive a single dose of unadjuvanted vaccine containing 30/60/120 µg of RSV fusion (F) protein stabilized in the prefusion conformation (RSVPreF3) or placebo., Results: Solicited local adverse events (AEs) were more frequently reported in the RSVPreF3 groups (4%-53.2%) versus placebo (0%-15.9%); most were mild/moderate. Unsolicited AEs were comparably reported among groups. Three serious AEs were reported; none was vaccination-related. Compared with prevaccination values, anti-RSV A neutralizing antibody geometric mean titers and anti-RSVPreF3 immunoglobulin G geometric mean concentrations increased 8- to 14-fold and 12- to 21-fold at day 8 and persisted 5- to 6-fold and 6- to 8-fold higher until day 91 in the RSVPreF3 groups versus 1-fold in placebo. Comparisons at day 8 and day 31 showed that the higher dose levels were significantly more immunogenic than the lowest one., Conclusions: The RSVPreF3 vaccine was well tolerated and immunogenic. The 60 and 120 µg dose levels were selected for further investigation in pregnant women., Clinical Trials Registration: NCT03674177., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: There is an urgent need for improved influenza vaccines especially for older adults due to the presence of immunosenescence. It is therefore highly relevant to compare enhanced influenza vaccines with traditional influenza vaccines with respect to their effectiveness., Objective: To compare vaccine efficacy and effectiveness of adjuvanted influenza vaccines (aTIV/aQIV) vs. non-adjuvanted standard-dose (TIV/QIV) and high-dose (TIV-HD/QIV-HD) influenza vaccines regarding influenza-related outcomes in older adults, complementing findings from the European Centre for Disease Prevention and Control (ECDC)'s systematic review of enhanced seasonal influenza vaccines from February 2020., Methods: A systematic literature search was conducted in Embase and MEDLINE to identify randomised controlled trials, observational studies and systematic reviews, published since ECDC's systematic review (between 7 February 2020 and 6 September 2021). Included studies were appraised with either the Cochrane Risk of Bias tool, ROBINS-I or AMSTAR 2., Results: Eleven analyses from nine real-world evidence (RWE) studies comprising ∼53 million participants and assessing the relative vaccine effectiveness (rVE) of aTIV vs. TIV, QIV and/or TIV-HD in adults aged ≥65 years over the 2006/07-2008/09 and 2011/12-2019/20 influenza seasons were identified. Nine analyses found that aTIV was significantly more effective than TIV and QIV in reducing influenza-related outcomes by clinical setting and suspected influenza outbreaks (rVE ranging from 7.5% to 25.6% for aTIV vs. TIV and 7.1% to 36.3% for aTIV vs. QIV). Seven analyses found similar effectiveness of aTIV vs. TIV-HD in reducing influenza-related medical encounters, inpatient stays and hospitalisations/emergency room visits. In three analyses, aTIV was significantly more effective than TIV-HD in reducing influenza-related medical encounters and office visits (rVE ranging from 6.6% to 16.6%). Risk of bias of identified studies was moderate to high., Conclusions: Our study suggests that both adjuvanted and high-dose vaccines are effective alternatives for vaccination programmes in older adults and preferable over conventional standard-dose vaccines., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: TW, KW, AK, DB and TFS have received honoraria from Seqirus GmbH for their contribution to this work. KJS was employed by Xcenda GmbH which received funding from Seqirus GmbH., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The currently licensed quadrivalent MenACWY-CRM conjugate vaccine presentation consists of two vials (lyophilised MenA and liquid MenCWY) to be reconstituted before injection. A new fully liquid formulation in a single vial has been developed to further improve the vaccine presentation. Since the MenA structure is subject to hydrolytic degradation, this study was conducted to compare the immunogenicity and safety of the investigational MenACWY-CRM liquid vaccine with the licensed vaccine., Methods: In this multicentre, randomised, controlled, observer-blind, phase 2b study, 979 healthy adults were administered a single dose of MenACWY-CRM liquid presentation or the currently licensed MenACWY-CRM vaccine. MenA free saccharide generation was accelerated to approximately 30% in the liquid presentation and MenA polysaccharide O-acetylation was reduced to approximately 40%, according to a controlled procedure. Immunological non-inferiority of the MenACWY-CRM liquid to the licensed vaccine, as measured by human serum bactericidal assay (hSBA) geometric mean titres (GMTs) against MenA 1 month post-vaccination, was the primary study objective. Safety assessment was among the secondary objectives., Results: Immune responses against each serogroup were similar between the two vaccine groups and was non-inferior for MenA. Adjusted hSBA GMTs for MenA were 185.16 and 211.33 for the MenACWY-CRM liquid presentation and currently licensed vaccine presentation, respectively. The between-group ratio of hSBA GMTs for MenA was 0.88, with a two-sided 95% confidence interval lower limit of 0.64, greater than the prespecified non-inferiority margin of 0.5, thus meeting the primary study objective. Both vaccines were well tolerated. No serious adverse events were considered related to vaccination., Conclusions: The levels of MenA free saccharide and polysaccharide O-acetylation did not affect the immunogenicity of the fully liquid presentation, which was demonstrated to be non-inferior to the immunogenicity of the currently licensed MenACWY-CRM vaccine against MenA. The immunogenicity, reactogenicity and safety profiles of the two vaccine presentations were similar., Competing Interests: Declaration of Competing Interest TA, SVH, MA, BK, BdW, GFDD, MC, PVS, EF, ML and MP are employed by the GSK group of companies. TA, MA, BdW, PVS, EF, ML and MP hold shares in the GSK group of companies. CV reports her institution received payments from the GSK group of companies, MSD and Pfizer, outside the submitted work. ILR reports her institution received payments from the GSK group of companies for the conduct of the study. TN reports payments from the GSK group of companies, Merck, Sanofi Pasteur and Seqirus, outside the submitted work. TA, SVH, MA, BK, BdW, GFDD, MC, PVS, EF, ML, MP, CV, ILR and TN declare no other financial and non-financial relationships and activities. JV, TS, GG, MF, GI, TFS, AMN and SC declare no financial and non-financial relationships and activities and no conflicts of interest., (Copyright © 2021 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd.. All rights reserved.)

Background: Respiratory syncytial virus (RSV) is a common cause of respiratory tract illness and hospitalization in neonates and infants. RSV vaccination during pregnancy may protect offspring in their first months of life., Methods: This randomized, observer-blind, multicenter, phase 2 study evaluated the immunogenicity and safety of an RSV candidate vaccine in healthy nonpregnant women aged 18-45 years. Four hundred participants were randomized (1:1:1:1) to receive a single intramuscular dose of vaccine containing 30 µg, 60 µg, or 120 µg of RSV fusion protein engineered to preferentially maintain a prefusion conformation (RSV-PreF vaccine) or placebo., Results: Thirty days postvaccination, RSV-A neutralizing antibody geometric mean titers (GMTs) increased 3.75-, 4.42- and 4.36-fold; RSV-B neutralizing antibody GMTs 2.36-, 2.54- and 2.76-fold; and palivizumab competing antibody (PCA) concentrations 11.69-, 14.38- and 14.24-fold compared with baseline levels in the 30 µg, 60 µg, and 120 µg RSV-PreF groups, respectively. Antibody titers and PCA concentrations at day 30 were significantly higher with the 120 µg compared to the 30 µg RSV-PreF vaccine. All RSV-PreF vaccine formulations and the placebo had similar reactogenicity profiles. No serious adverse events were considered to be related to the RSV-PreF vaccine., Conclusions: The 3 formulations of the investigational RSV-PreF vaccine were well-tolerated and induced RSV-A and RSV-B neutralizing antibodies and PCAs in healthy, nonpregnant women., Clinical Trials Registration: NCT02956837., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

This analysis focused on long-term cross-reactive immunogenicity against nonvaccine human papillomavirus (HPV) types 31 and 45 following 2 doses of AS04-adjuvanted HPV-16/18 vaccine in girls aged 9-14 years or following 3 doses in women aged 15-25 years, for up to 3 years (HPV-070 study) and up to 5 years (HPV-048 study) after the first vaccination. Both schedules elicited antibodies against HPV-31 and HPV-45 up to 5 years after first dose. The antibody concentration was similar in young girls as compared to women. Specific CD4+ T-cell and B-cell responses to HPV-31 and HPV-45 at month 36 were similar across groups. Clinical trials registration: NCT01381575 and NCT00541970., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

This study assessed long-term immunogenicity and safety following 3 doses of AS04-adjuvanted human papillomavirus (HPV)-16/18 L1 virus-like particle (VLP) vaccine in females 10-14 years old. Girls included in the immunogenicity subset in the primary controlled, observer-blinded, randomized study (NCT00196924) who received 3 doses were invited for a 10-year follow-up (NCT00316706 and NCT00877877). Serum antibody responses against HPV-16/18 (vaccine types) and HPV-31/45 (non-vaccine types) were measured by enzyme-linked immunosorbent assay (ELISA) using type-specific VLP as coating antigens. Serious adverse events (SAEs) and pregnancy information were recorded. At Month (M) 120, all subjects (N = 418, according-to-protocol immunogenicity cohort) were seropositive for anti-HPV-16/18 antibodies. Geometric mean titers (GMTs) were 1589.9 ELISA Units [EU]/mL (95% confidence interval [CI]: 1459.8-1731.6) for anti-HPV-16 and 597.2 EU/mL (95% CI: 541.7-658.5) for anti-HPV-18 in subjects seronegative at baseline for the type analyzed. Post hoc mathematical modeling predicted a durability ≥50 years for anti-HPV-16 and anti-HPV-18. For the non-vaccine humoral type response, all initially seronegative subjects had seroconverted at M7, with anti-HPV-31 GMT of 2030.5 EU/mL (95% CI: 1766.2-2334.4) and anti-HPV-45 GMT of 2300.8 EU/mL (95% CI: 2036.8-2599.0). At M120, 87.7% and 85.1% remained seropositive for anti-HPV-31 with GMT of 242.9 EU/mL (95% CI: 201.4-293.0) and anti-HPV-45 with GMT of 204.7 EU/mL (95% CI: 170.0-246.6). During the 10-year follow-up, no SAEs or abnormal pregnancy outcomes were causally related to vaccination. Three doses of the AS04-HPV-16/18 vaccine induced high and sustained antibody response against HPV-16,18,31 and 45 in girls aged 10-14 years during the 10-year follow-up, with an acceptable long-term safety profile.

We evaluated antibody persistence against hepatitis B virus (HBV) in adolescents previously vaccinated with a hexavalent diphtheria-tetanus-acellular pertussis-HBV-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine (DTPa-HBV-IPV/Hib), as part of the national newborn immunization program in Germany. We also assessed the anamnestic response to a challenge dose of a monovalent HBV vaccine. In this phase 4, open-label, non-randomized study (NCT02798952), 302 adolescents aged 14-15 years, primed in their first 2 years of life with 4 DTPa-HBV-IPV/Hib doses, received one challenge dose of monovalent HBV vaccine. Blood samples were taken before and one month post-vaccination and used to determine antibody levels against hepatitis B surface antigen (HBs). Reactogenicity and safety were also assessed post-challenge dose. Pre-challenge dose, 53.7% of 268 participants included in the according-to-protocol cohort for immunogenicity had anti-HBs antibody concentrations ≥10 mIU/mL (seroprotection cut-off) and 16.8% had anti-HBs antibody concentrations ≥100 mIU/mL. One month post-challenge dose, 93.3% of adolescents had anti-HBs antibody concentrations ≥10 mIU/mL and 87.3% had antibody concentrations ≥100 mIU/mL. An anamnestic response was mounted in 92.5% of adolescents. Injection site pain (in 33.6% of participants) and fatigue (30.2%) were the most frequently reported solicited local and general symptoms, respectively. Six of the 55 unsolicited adverse events reported were considered vaccination-related. Two vaccination-unrelated serious adverse events were reported during the study. Long-term antibody persistence against hepatitis B was observed in 14-15 years old adolescents previously primed in infancy with DTPa-HBV-IPV/Hib. A challenge dose of monovalent HBV vaccine induced strong anamnestic response, with no safety concerns.

Background: This study evaluated the immunogenicity and safety of quadrivalent meningococcal conjugate vaccine using tetanus (T) toxoid as carrier protein (MenACWY-TT) co-administered with combined diphtheria-tetanus-acellular pertussis vaccine (Tdap) versus their separate administration in adolescents and young adults., Methods: In this phase III, randomized, partially-blind study (NCT01767376), healthy 11-25-year-olds (N = 660) were randomized (1:1:1) to receive MenACWY-TT and Tdap at Month 0 (Co-ad group), MenACWY-TT at Month 0 and Tdap at Month 1 (ACWY_Tdap group) or Tdap at Month 0 and MenACWY-TT at Month 1 (Tdap_ACWY group). Immune responses to MenACWY-TT were measured by serum bactericidal assay using rabbit complement (rSBA). Anti-diphtheria (D), anti-tetanus (T), anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibody concentrations were assessed using enzyme-linked immunosorbent assays. Non-inferiority of immunogenicity was assessed using pre-defined clinical criteria. Safety was also evaluated., Results: Non-inferiority of immunogenicity of MenACWY-TT and Tdap when co-administered versus their separate administration was demonstrated in terms of rSBA geometric mean titers (GMTs) for 4 meningococcal serogroups and of the percentage of participants with antibody concentrations >1 IU/ml for D and T. Among the pertussis antigens, non-inferiority criteria for geometric mean concentrations (GMCs) were reached for PT, but not met for FHA and PRN. Across all groups, ≥93.2% of participants had vaccine responses to each meningococcal serogroup, ≥99.1% were seroprotected against T and D, and ≥85.5% had booster responses to each pertussis antigen. Robust increases in antibody GMTs/GMCs were observed for all antigens between pre-and post-vaccination. Both vaccines had clinically acceptable safety profiles., Conclusion: Immune responses to MenACWY-TT and to the T and D antigens from Tdap were not impacted by their co-administration. The lower antibody concentrations observed against the pertussis components may be of limited clinical relevance since robust anti-pertussis booster responses were observed. This study supports concurrent administration of the 2 vaccines in adolescents., (Copyright © 2018 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.)

Background: In adults aged ≥60 years, two doses of the herpes zoster subunit vaccine (HZ/su; 50 µg varicella-zoster virus glycoprotein E [gE] and AS01 B Adjuvant System) elicited humoral and cell-mediated immune responses persisting for at least six years. We assessed immunogenicity nine years post-initial vaccination., Methods: This open extension study (NCT02735915) followed 70 participants who received two HZ/su doses in the initial trial (NCT00434577). Blood samples to assess the cellular (intracellular cytokine staining) and humoral (ELISA) immunity were taken at year nine post-initial vaccination., Results: Participants' mean age at dose 1 was 72.3 years. The fold increases over pre-vaccination in the mean frequency of gE-specific CD4+ T-cells expressing ≥2 activation markers plateaued from year four post-dose 1 until year nine. Anti-gE antibody geometric mean concentrations plateaued and remained above pre-vaccination levels from year four onwards. Immunogenicity at year nine was similar across age strata (60-69, ≥70 years) and confirmed statistical prediction model results using data for up to year six. Further modeling using all data up to year nine predicted immune responses would remain above the pre-vaccination level up to year 15., Conclusion: In adults aged ≥60 years, HZ/su-induced immunogenicity remained above pre-vaccination levels for at least nine years post-initial vaccination., Summary: After vaccination with HZ/su, both cell mediated and humoral immunity remained above pre-vaccination levels up to year 9 regardless of age group. Immune responses are predicted to remain above baseline up to 15 years post initial vaccination.