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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 AS01E-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°6. 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-PER-confirmed RSV-related lower respiratory tract disease was 82.6% (96.95% confidence interval [CI], 5Z9 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 R.SV-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°6, 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 KSV-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.). [ABSTRACT FROM AUTHOR]

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: Determinants of maternal-fetal cytomegalovirus (CMV) transmission and factors influencing the severity of congenital CMV (cCMV) infection are not well understood., Methods: We conducted a descriptive, multi-center study in pregnant women ≥18 years old with primary CMV infection and their newborns (NCT01251744) to explore maternal immune responses to CMV and determine potential immunologic/virologic correlates of cCMV following primary infection during pregnancy. We developed alternative approaches looking into univariate/multivariate factors associated with cCMV, including a participant clustering/stratification approach and an interpretable predictive model-based approach using trained decision trees for risk prediction (post-hoc analyses)., Results: Pregnant women were grouped in three distinct clusters with similar baseline characteristics, particularly gestational age at diagnosis. We observed a trend for higher viral loads in urine and saliva samples from mothers of infants with cCMV versus without cCMV. When using a trained predictive-model approach that accounts for interaction effects between variables, anti-pentamer IgG antibody concentration and viral load in saliva were identified as biomarkers jointly associated with the risk of maternal-fetal CMV transmission., Conclusion: We identified biomarkers of CMV maternal-fetal transmission. After validation in larger studies, our findings will guide the management of primary infection during pregnancy and the development of vaccines against cCMV., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Previous phase 3 studies showed that the AS01 E -adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine for older adults (RSVPreF3 OA) is well tolerated and efficacious in preventing RSV-associated lower respiratory tract disease in adults ≥ 60 years of age. This study evaluated lot-to-lot immunogenicity consistency, reactogenicity, and safety of three RSVPreF3 OA lots., Methods: This phase 3, multicenter, double-blind study randomized (1:1:1) participants ≥ 60 years of age to receive one of three RSVPreF3 OA lots. Serum RSVPreF3-binding immunoglobulin G (IgG) concentration was assessed at baseline and 30 days post-vaccination. Lot-to-lot consistency was demonstrated if the two-sided 95 % confidence intervals (CIs) of the RSVPreF3-binding IgG geometric mean concentration (GMC) ratios between each lot pair at 30 days post-vaccination were within 0.67 and 1.50. Solicited adverse events (AEs) within four days, unsolicited AEs within 30 days, and serious AEs (SAEs) and potential immune-mediated diseases within six months post-vaccination were recorded., Results: A total of 757 participants received RSVPreF3 OA, of whom 708 were included in the per-protocol set (234, 237, and 237 participants for each lot). Lot-to-lot consistency was demonstrated: GMC ratios were 1.06 (95 % CI: 0.94-1.21), 0.92 (0.81-1.04), and 0.87 (0.77-0.99) between the lot pairs (lot 1/2; 1/3; 2/3). For the three lots, the RSVPreF3-binding IgG concentration increased 11.84-, 11.29-, and 12.46-fold post-vaccination compared to baseline. The reporting rates of solicited and unsolicited AEs, SAEs, and potential immune-mediated diseases were balanced between lots. Twenty-one participants reported SAEs; one of these-a case of atrial fibrillation-was considered by the investigator as vaccine-related. SAEs with a fatal outcome were reported for four participants, none of which were considered by the investigator as vaccine-related., Conclusion: This study demonstrated lot-to-lot immunogenicity consistency of three RSVPreF3 OA vaccine lots and indicated that the vaccine had an acceptable safety profile.ClinicalTrials.gov: NCT05059301., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Alexander Murray (AM) reports a relationship with PharmQuest that includes: employment. AM reports that payments were made by GSK to his institution as clinical research trial site. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Aurelie Olivier (AO) reports a relationship with GSK that includes: employment and equity or stocks. Aurelie Olivier (AO) has patent pending to GSK. AO is an employee of GSK at the time the study was designed, initiated, and/or conducted. AO holds shares of stock in the company as part of their employee remuneration. AO is co-applicants on a pending patent filed by GSK. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Franck Maschino (FM) reports a relationship with GSK that includes: employment and equity or stocks. FM is an employee of GSK at the time the study was designed, initiated, and/or conducted. FM holds shares of stock in the company as part of their employee remuneration. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Johan Sanmartin Berglund (JSB) reports a relationship with Blekinge Institute of Technology that includes: employment. Johan Sanmartin Berglund (JSB) has nothing else to disclose. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Lew Pliamm (LP) reports a relationship with Canadian Phase Onward Inc. that includes: employment. LP has nothing else to disclose. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Lars Rombo (LR) reports a relationship with Clinical Research Centre Sörmland that includes: employment. LR reports that payment was made by GSK to his institution for conducting the study. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Murdo Ferguson (MF) reports a relationship with Colchester Research Group (CRG) that includes: employment. MF is employed by CRG which was contracted by GSK to execute the study. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Marie-Pierre David (M-PD) reports a relationship with GSK that includes: employment and equity or stocks. Marie-Pierre David (M-PD) has patent pending to GSK. M-PD is an employee of GSK at the time the study was designed, initiated, and/or conducted. M-PD holds shares of stock in the company as part of their employee remuneration. M-PD is co-applicants on a pending patent filed by GSK. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Nathalie De Schrevel (NDS) reports a relationship with GSK that includes: employment and equity or stocks. NDS is an employee of GSK at the time the study was designed, initiated, and/or conducted. NDS holds shares of stock in the company as part of their employee remuneration. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Shady Kotb (SK) reports a relationship with GSK that includes: employment and equity or stocks. SK is an employee of GSK at the time the study was designed, initiated, and/or conducted. SK holds shares of stock in the company as part of their employee remuneration. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors reports financial support was provided by GlaxoSmithKline Biologicals SA. Veronica Hulstrom reports a relationship with GSK that includes: employment and equity or stocks. VH is an employee of GSK at the time the study was designed, initiated, and/or conducted. VH holds shares of stock in the company as part of their employee remuneration. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 GSK.)

Background: In the previous (parent) study, 2 doses of different formulations of an investigational vaccine against respiratory syncytial virus (RSVPreF3 OA) were well tolerated and immunogenic in older adults. This multicenter phase 2b extension study assessed safety and immunogenicity of a revaccination (third) dose of the 120 μg RSVPreF3-AS01E formulation., Methods: In total, 122 older adults (60-80 years), previously vaccinated with 2 doses of RSVPreF3-AS01E formulations (containing 30, 60, or 120 μg RSVPreF3 antigen), received an additional 120 μg RSVPreF3-AS01E dose 18 months after dose 2. Vaccine safety was evaluated in all participants up to 6 months and immunogenicity in participants who received 120 μg RSVPreF3-AS01E doses until 1 month after dose 3., Results: Similar to the parent study, mostly mild-to-moderate solicited adverse events and no vaccine-related serious adverse events or potential immune-mediated disorders were reported. Neutralizing titers and cell-mediated immune responses persisted for 18 months after 2-dose vaccination. Dose 3 increased RSV-specific neutralizing titers against RSV-A and RSV-B and median CD4+ T-cell frequencies. After dose 3, RSV-specific neutralizing titers but not CD4+ T-cell frequencies were below levels detected 1 month after dose 1., Conclusions: Revaccination with 120 μg RSVPreF3-AS01E 18 months after dose 2 is well tolerated and immunogenic in older adults., Clinical Trials Registration: NCT04657198; EudraCT, 2020-000692-21., Competing Interests: Potential conflicts of interest. I. L. R. reports funding from Icosavax and Virometix to her institution for the conduct of RSV vaccine trials, and from GSK to her institution for conduct of this clinical trial. M. V. R. reports GSK funding to the Leuven University Vaccinology Center for the conduct of the clinical trial. C. Vm. reports GSK funding to her institution for the conduct of the clinical trial as at the time of the execution of the clinical trial she was an investigator; C. Vm. joined GSK after the close of the study at her institution and is currently an employee of GSK; however, she does not hold any shares. C. V. A., N. D. S., B. S., C. V., M. P. D., S. K., and V. H. were employees of GSK at the time of the study conduct. N. D. S., B. S., M. P. D., C. V., S. K., and V. H. hold shares from GSK as part of their past/current employee remuneration. All current/previous employees of GSK declare financial and nonfinancial relationships and activities. 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.)

Developing a vaccine to prevent congenital cytomegalovirus (CMV) infection and newborn disability requires an understanding of infection incidence. In a prospective cohort study of 363 adolescent girls (NCT01691820), CMV serostatus, primary infection, and secondary infection were determined in blood and urine samples collected at enrollment and every 4 months for 3 years. Baseline CMV seroprevalence was 58%. Primary infection occurred in 14.8% of seronegative girls. Among seropositive girls, 5.9% had ≥4-fold increase in anti-CMV antibody, and 23.9% shed CMV DNA in urine. Our findings provide insights on infection epidemiology and highlight the need for more standardized markers of secondary infection., Competing Interests: Potential conflicts of interest. M. D., N. D. S., A. G., A. A. P., F. R., J. Y., and I. D. are employed by and hold shares of GSK. J.-M. D. and L. G. are employees of GSK. R. P. was an employee of GSK at the time of the study; he holds shares of GSK, is currently an employee of Moderna Inc, and holds shares of Moderna Inc. D. A. and S. B. received a grant from GSK for this study. S. B. is a member of advisory committees for Merck, Moderna Therapeutics, and Sanofi, and received grants from Pfizer and Moderna outside the submitted work. E. M. Y. reports no potential conflicts. The 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.)

The RSVPreF3-AS01 vaccine, containing the respiratory syncytial virus (RSV) prefusion F protein and the AS01 adjuvant, was previously shown to boost neutralization responses against historical RSV strains and to be efficacious in preventing RSV-associated lower respiratory tract diseases in older adults. Although RSV F is highly conserved, variation does exist between strains. Here, we characterized variations in the major viral antigenic sites among contemporary RSV sequences when compared with RSVPreF3 and showed that, in older adults, RSVPreF3-AS01 broadly boosts neutralization responses against currently dominant and antigenically distant RSV strains. RSV-neutralizing responses are thought to play a central role in preventing RSV infection. Therefore, the breadth of RSVPreF3-AS01-elicited neutralization responses may contribute to vaccine efficacy against contemporary RSV strains and those that may emerge in the future.

Background: The aim of this study was to investigate safety and immunogenicity of vaccine formulations against respiratory syncytial virus (RSV) containing the stabilized prefusion conformation of RSV fusion protein (RSVPreF3)., Methods: This phase 1/2, randomized controlled, observer-blind study enrolled 48 young adults (YAs; aged 18-40 years) and 1005 older adults (OAs; aged 60-80 years) between January and August 2019. Participants were randomized into equally sized groups to receive 2 doses of unadjuvanted (YAs and OAs) or AS01-adjuvanted (OAs) vaccine or placebo 2 months apart. Vaccine safety and immunogenicity were assessed until 1 month (YAs) or 12 months (OAs) after second vaccination., Results: The RSVPreF3 vaccines boosted humoral (RSVPreF3-specific immunoglobulin G [IgG] and RSV-A neutralizing antibody) responses, which increased in an antigen concentration-dependent manner and were highest after dose 1. Compared to prevaccination, the geometric mean frequencies of polyfunctional CD4+ T cells increased after each dose and were significantly higher in adjuvanted than unadjuvanted vaccinees. Postvaccination immune responses persisted until end of follow-up. Solicited adverse events were mostly mild to moderate and transient. Despite a higher observed reactogenicity of AS01-containing vaccines, no safety concerns were identified for any assessed formulation., Conclusions: Based on safety and immunogenicity profiles, the AS01E-adjuvanted vaccine containing 120 μg of RSVPreF3 was selected for further clinical development., Clinical Trials Registration: NCT03814590., Competing Interests: Potential conflicts of interest. D. C., M.-P. D., M. d. H., N. D. S., N. D., L. F., V. H., J. K., N. M., B. S., F. S., J. T., C. V. A., and C. Ve. are/were employees of the GSK group of companies at the time of the study conduct. C. Va. is currently an employee of the GSK group of companies. D. C., M.-P. D., M. d. H., N. D. S., N. D., B. S., F. S., and C. Ve. hold shares from the GSK group of companies as part of their past/current employee remuneration. F. S. is currently an employee of Janssen Pharmaceutical Companies of Johnson & Johnson and holds restricted shares from Johnson & Johnson as part of his employee remuneration. All current/previous employees of the GSK groups of companies declare financial and nonfinancial relationships and activities. C. P. A., E. K., I. L.-R., K. S., and C. Va. report grant/research support from the GSK group of companies to their institution for study conduct and, except for C. Va., they have no nonfinancial relationships and activities to declare. E. K. has served as consultant, in advisory boards, in speaker’s bureaus, or received travel reimbursement from Amphastar, AstraZeneca, Boehringer Ingelheim, Forest, Cipla, Chiesi, GSK, Mylan, Novartis, Sunovion, Teva, Pearl Pharmaceuticals, and Theravance. 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) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Respiratory syncytial virus (RSV) causes lower respiratory tract infection, with a high burden of disease among adults ≥60 years. This study assessed the safety, reactogenicity, and immunogenicity of an investigational adjuvanted RSV vaccine (RSVPreF3/AS01 B ) in Japanese adults aged 60-80 years., Methods: Forty participants were randomized to receive two doses of RSVPreF3/AS01 B or the placebo, in a 1:1 ratio, two months apart, in this placebo-controlled study. Solicited administration-site and systemic adverse events (AEs) were collected within 7 days and unsolicited AEs within 30 days post-vaccination. Serious AEs (SAEs) and potential immune-mediated diseases (pIMDs) were collected throughout the study (12 months post-dose 2). RSVPreF3-specific immunoglobulin G (IgG) antibody concentrations and neutralizing antibody (nAb) titers against RSV-A were evaluated on day (D)1, D31, D61, D91 and those against RSV-B on D1, D31, D91., Results: Solicited AEs were reported more frequently in RSVPreF3/AS01 B recipients (80.0%-90.0%) than in placebo recipients (10.0%-20.0%). Two RSVPreF3/AS01 B recipients experienced grade 3 solicited AEs. Rate of unsolicited AEs were similar (30.0%-35.0%) in both groups. No RSVPreF3/AS01 B recipient reported SAEs/pIMDs, while one placebo recipient reported two SAEs that were unrelated to vaccination. Baseline RSVPreF3-specific IgG and RSV-A/-B nAb levels were above the assay cut-off values. In the RSVPreF3/AS01 B group, RSVPreF3-specific IgG concentrations increased 12.8-fold on D31 and 9.2-fold on D91 versus baseline while nAb titers increased 7.3-fold (RSV-A) and 8.4-fold (RSV-B) on D31 and 6.3-fold (RSV-A) and 9.9-fold (RSV-B) on D91., Conclusions: The RSVPreF3/AS01 B vaccine was well tolerated and immunogenic in older Japanese adults., Clinical Trial Registration Number: NCT04090658., Competing Interests: Conflict of interest SK, NF, PN, CV, NDeS, MPD, NM and VH are or were employees of the GSK group of companies and declare financial and non-financial relationships and activities. SK, CV, NDeS, MPD, NM and VH hold or held shares in the GSK group of companies as part of their employee remuneration. MH has nothing to disclose., (Copyright © 2022 [The Author/The Authors]. Published by Elsevier B.V. All rights reserved.)

Background: A previous phase 2 study demonstrated the immunogenicity of a single dose of meningococcal A, C, W, Y-tetanus toxoid conjugate (MenACWY-TT) or polysaccharide (MenACWY-PS) vaccine for up to 5 years in individuals aged 11-55 years. This follow-up study evaluated long-term antibody persistence up to 10 years and the immunogenicity and safety of a single MenACWY-TT booster dose given 10 years after primary vaccination., Methods: Blood draws were conducted annually in Years 7-10. At Year 10, all subjects received a MenACWY-TT booster dose. Blood was drawn at 1 month and safety data were collected ≤6 months postbooster. Study endpoints included immunogenicity during the persistence phase (primary), and immunogenicity and safety during the booster phase (secondary). Statistical analyses were descriptive., Results: A total of 311 subjects were enrolled in the persistence phase (MenACWY-TT, 235; MenACWY-PS, 76); 220 were enrolled in the booster phase (MenACWY-TT, 164; MenACWY-PS, 56). Descriptive analyses indicated that at Years 7-10, the percentages of subjects achieving serum bactericidal antibody assay using baby rabbit complement (rSBA) titers ≥1:8 and ≥1:128 were higher for serogroups A, W, and Y in the MenACWY-TT versus MenACWY-PS group; percentages were similar across groups for serogroup C. rSBA geometric mean titers (GMTs) for serogroups A, W, and Y were higher in the MenACWY-TT group and slightly higher in the MenACWY-PS group for serogroup C. One month postbooster, all primary MenACWY-TT and ≥98.1% of primary MenACWY-PS recipients had rSBA titers ≥1:8. For all serogroups, rSBA GMTs postbooster were higher in the MenACWY-TT versus MenACWY-PS group. Most local and general reactogenicity events were similar between groups and mild to moderate in severity. Adverse events at 1 month postbooster were 9.1% for the MenACWY-TT and 3.6% for the MenACWY-PS groups; all were nonserious., Conclusions: Immune responses to a single MenACWY-TT primary dose administered at age 11-55 years persisted in >70% of individuals evaluated at Years 7-10. A MenACWY-TT booster dose administered at Year 10 was safe and immunogenic with no new safety signals observed. These results provide important insights regarding long-term protection from primary vaccination and the benefits of booster dosing., Trial Registration: Clinicaltrials.gov, NCT01934140. Registered September 2013.

This phase 3B, open-label, extension study (NCT01962207) evaluated long-term persistence of antibodies induced by the quadrivalent meningococcal vaccine conjugated to tetanus toxoid (MenACWY-TT) compared with the meningococcal serogroup C vaccine conjugated to CRM (MenC-CRM) and the quadrivalent meningococcal polysaccharide vaccine (MenACWY-PS) 6 to 10 y after primary vaccination in toddlers (aged 1-<2 y; MenACWY-TT and MenC-CRM) and children (aged 2-<11 y; MenACWY-TT and MenACWY-PS). Antibody responses against meningococcal serogroups A, C, W, and Y were assessed by serum bactericidal antibody assays using rabbit (rSBA) or human (hSBA) complement. A MenACWY-TT booster dose at Year 10 was given to all eligible subjects regardless of the primary vaccine received. At Year 10, the percentages of subjects with rSBA titers ≥1:8 for serogroups A, C, W, and Y were as follows: MenACWY-TT (toddlers), 65.6%, 82.8%, 31.3%, 43.8%, respectively; MenC-CRM, 88.2% for serogroup C; MenACWY-TT (children), 88.9%, 84.1%, 67.1%, 65.9%; and MenACWY-PS, 28.6%, 81.0%, 23.8%, and 23.8%. Corresponding percentages for hSBA titers ≥1:4 were as follows: MenACWY-TT (toddlers), 31.1%, 91.9%, 44.4%, 41.4%; MenC-CRM, 93.8% for serogroup C; MenACWY-TT (children), 34.8%, 91.1%, 61.2%, 72.6%; and MenACWY-PS, 33.3%, 100.0%, 26.3%, and 44.4%. One month after the MenACWY-TT booster, the percentage of subjects with vaccine response ranged from 75.7% to 100.0% across serogroups in all study groups. Postbooster vaccine responses were generally comparable between groups across serogroups. No new safety signals were identified. Antibody responses persisted 10 y after MenACWY-TT vaccination. The MenACWY-TT booster dose was well tolerated and elicited robust immune responses.