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Background: Emerging data suggest that second-generation influenza vaccines with higher hemagglutinin (HA) antigen content and/or different production methods may induce stronger antibody responses to HA than standard-dose egg-based influenza vaccines in adults. We compared antibody responses to high-dose egg-based inactivated (HD-IIV3), recombinant (RIV4), and cell culture-based (ccIIV4) vs standard-dose egg-based inactivated influenza vaccine (SD-IIV4) among health care personnel (HCP) aged 18-65 years in 2 influenza seasons (2018-2019, 2019-2020).
Methods: In the second trial season, newly and re-enrolled HCPs who received SD-IIV4 in season 1 were randomized to receive RIV4, ccIIV4, or SD-IIV4 or were enrolled in an off-label, nonrandomized arm to receive HD-IIV3. Prevaccination and 1-month-postvaccination sera were tested by hemagglutination inhibition (HI) assay against 4 cell culture propagated vaccine reference viruses. Primary outcomes, adjusted for study site and baseline HI titer, were seroconversion rate (SCR), geometric mean titers (GMTs), mean fold rise (MFR), and GMT ratios that compared vaccine groups to SD-IIV4.
Results: Among 390 HCP in the per-protocol population, 79 received HD-IIV3, 103 RIV4, 106 ccIIV4, and 102 SD-IIV4. HD-IIV3 recipients had similar postvaccination antibody titers compared with SD-IIV4 recipients, whereas RIV4 recipients had significantly higher 1-month-postvaccination antibody titers against vaccine reference viruses for all outcomes.
Conclusions: HD-IIV3 did not induce higher antibody responses than SD-IIV4, but, consistent with previous studies, RIV4 was associated with higher postvaccination antibody titers. These findings suggest that recombinant vaccines rather than vaccines with higher egg-based antigen doses may provide improved antibody responses in highly vaccinated populations.
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http://dx.doi.org/10.1093/ofid/ofad223 | DOI Listing |
AAPS J
September 2025
Gene Transfer and Immunogenicity Branch, Division of Gene Therapy 2, Office of Gene Therapy, Office of Therapeutic Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, WO52 RM3124, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993-0002, USA.
As the field of gene therapy advances and as the importance of sex as a biological variable in shaping viral immune responses is recognized, the impact of sex on adeno-associated virus (AAV) vectors mediated gene therapies remain largely unexplored. Here we review current understanding of the immune response against AAV gene therapy as well as the knowledge of sex differences observed in viral responses. We discuss sex differences in innate immune mechanisms such as Toll-like receptor recognition and complement activation, as well as the functional responses of key immune cells such as dendritic cells, macrophages, and T/B cells that are involved in AAV immunogenicity.
View Article and Find Full Text PDFActa Pharmacol Sin
September 2025
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
The anti-HER2 antibody‒drug conjugate (ADC) DS-8201 presents new hope for patients with advanced HER2-positive tumors. Its clinical application, however, is hindered by serious adverse reactions and reduced efficacy following long-term treatment. In this study, we investigated the factors influencing the sensitivity of DS-8201 and developed effective combination regimens to optimize its therapeutic efficacy.
View Article and Find Full Text PDFMol Pharm
September 2025
Department of Biochemical Engineering, University College London, Gower Street, London, WC1E 6BT, U.K.
We built a custom device to subject an antibody fragment A33 Fab to controlled stress conditions that combined pH, temperature, agitation, and LED-based light exposure in polypropylene microplates; to simulate the real-world challenges it may encounter during storage and transportation and to evaluate the key degradation routes in Fab formulations. We also explored the addition of Tween 80 as a surfactant and the impact of plate surface siliconisation. Monomer loss and fragmentation was monitored by size-exclusion chromatography, aggregate formation determined by changes in hydrodynamic radius in DLS, and chemical modifications identified through intact mass analysis by LC-MS, and N-terminal sequencing.
View Article and Find Full Text PDFClin Lymphoma Myeloma Leuk
August 2025
Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address:
Background: Mogamulizumab is more effective in treating the blood component of mycosis fungoides (MF) and Sezary syndrome (SS), though some patients also experience significant skin improvement. The characteristics distinguishing those with a favorable skin response remain unclear.
Objectives: This study aimed to characterize MF/SS patients achieving skin response on mogamulizumab.
Transplant Cell Ther
September 2025
Fred Hutchinson Cancer Center, Seattle, WA, USA; University of Washington, Seattle, WA, USA.
Background: BCMA-directed chimeric antigen receptor (CAR)-T cell therapy represents a major therapeutic breakthrough for relapsed/refractory multiple myeloma (RRMM), offering deep and durable responses in heavily pretreated patients. However, a subset of patients experience early relapse or fail to respond, highlighting the need for strategies to enhance efficacy. Gamma-secretase inhibitors (GSIs) have been shown to increase surface BCMA expression on malignant plasma cells and may potentiate the activity of BCMA CAR-T cells, particularly in patients with low baseline BCMA antigen density.
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