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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: 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.)

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: The burden of human papillomavirus (HPV) in human immunodeficiency virus (HIV)-infected persons and solid organ transplant (SOT) recipients is high. Clinical trials on HPV vaccines in persons living with HIV and particularly in SOT recipients have been sparse to date, included low numbers of participants, and none of them assessed the 9-valent HPV (9vHPV) vaccine. We investigated the immunogenicity with respect to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 and the safety of the 9vHPV vaccine in persons living with HIV and recipients of a kidney, lung, or heart transplant., Methods: This is a phase III investigator-initiated study in 100 persons living with HIV (age 18-45 years) and 171 SOT recipients (age 18-55 years). The 9vHPV vaccine was administered at day 1, month 2, and month 6. Primary outcome was seroconversion rates to the 9vHPV types at month 7. Secondary outcomes were geometric mean titers (GMTs) and frequency of adverse events (AEs)., Results: All HIV-infected participants seroconverted for all HPV types, but seroconversion ranged from 46% for HPV45 to 72% for HPV58 in SOT recipients. GMTs ranged from 180 to 2985 mMU/mL in HIV-positive participants and from 17 to 170 mMU/mL in SOT recipients, depending on the HPV type. Injection-site AEs occurred in 62% of participants but were mostly mild or moderate in intensity. None of the reported serious adverse events were deemed vaccine related. No patients died during the study., Conclusions: Immunogenicity of the 9vHPV vaccine is high in persons living with HIV but suboptimal in SOT recipients. The vaccine is safe and well tolerated in both groups., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

In this observational study, mumps-specific in vitro lymphoproliferation was measured in 24 subjects with low antibody titers and 24 subjects with high antibody titers who received their last vaccine dose up to 16 years previously. Overall, a significant lymphoproliferative response was found in 32 subjects (66.7%)-namely, in 13 (54.2%) of those with low antibody titers and 19 (79.2%) of those with high antibody titers. The mean stimulation index for subjects with low antibody titers was 4.47, whereas that for subjects with high antibody titers was 8.31 (P = .032). Mumps vaccine-induced cell-mediated immunity appears to be more persistent than the antibody response.

Background: To protect a naive global population against pandemic influenza, pandemic vaccines should be effective at low antigen doses, because of limited manufacturing capacity., Methods: In a multicenter, randomized, blind-observer phase 1 trial, groups of 50 healthy young adults received 2 doses, 21 days apart, of influenza A/Vietnam/1194/2004 NIBRG-14 (H5N1) vaccine containing 1.9, 3.8, 7.5 or 15 microg of hemagglutinin with oil-in-water emulsion adjuvant or 7.5 microg of hemagglutinin without adjuvant. Safety was monitored to day 42. Homologous hemagglutination-inhibition (HI) and microneutralization titers were determined after each vaccination. Cross-reactivity against A/Indonesia/05/2005 RG2 was tested after the second vaccination., Results: No vaccine-related significant or serious adverse events occurred. Injection site reactions, but not systemic reactions, were more frequent with adjuvant than without. Even with only 1.9 microg of hemagglutinin plus adjuvant, 72% of subjects had HI titers >or=1:32 after 2 doses. This proportion was 81%-89% with higher adjuvanted doses but was only 34% without adjuvant. Adjuvanted vaccine induced cross-neutralizing antibodies in 39%-65% of samples, versus 7% without adjuvant., Conclusions: The emulsion-adjuvanted pandemic influenza vaccine candidate was safe, immunogenic, and induced cross-reactive antibodies. This adjuvanted 1.9-microg candidate is the lowest effective dose tested to date. This could have a major impact on prepandemic vaccination strategies with stockpiled batches of vaccine., Trial Registration: ClinicalTrials.gov identifier: NCT00457509 .

Background: To date, there is no commercially available vaccine to prevent infectious mononucleosis, a disease frequently induced by Epstein-Barr virus (EBV) infection in adolescents or adults devoid of preexisting immunity to the virus., Methods: A total of 181 EBV-seronegative, healthy, young adult volunteers were randomized in a double-blind fashion to receive either placebo or a recombinant EBV subunit glycoprotein 350 (gp350)/aluminum hydroxide and 3-O-desacyl-4'-monophosphoryl lipid A (AS04) candidate vaccine in a 3-dose regimen., Results: The vaccine had demonstrable efficacy (mean efficacy rate, 78.0% [95% confidence interval {CI}, 1.0%-96.0%]) in preventing the development of infectious mononucleosis induced by EBV infection, but it had no efficacy in preventing asymptomatic EBV infection. One month after receipt of the final dose of gp350 vaccine, 98.7% of subjects showed seroconversion to anti-gp350 antibodies (95% CI, 85.5%-97.9%), and they remained anti-gp350 antibody positive for >18 months. Furthermore, there were no concerns regarding the safety or reactogenicity of the gp350/AS04 vaccine., Conclusion: These data support the clinical feasibility of using an EBV vaccine to prevent infectious mononucleosis., Trial Registration: ClinicalTrials.gov identifier: NCT00430534.