The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant of concern comprises several sublineages, with BA.2 and BA.2.12.1 having replaced the previously dominant BA.1 and with BA.4 and BA.5 increasing in prevalence worldwide. We show that the large number of Omicron sublineage spike mutations leads to enhanced angiotensin-converting enzyme 2 (ACE2) binding, reduced fusogenicity, and severe dampening of plasma neutralizing activity elicited by infection or seven clinical vaccines relative to the ancestral virus. Administration of a homologous or heterologous booster based on the Wuhan-Hu-1 spike sequence markedly increased neutralizing antibody titers and breadth against BA.1, BA.2, BA.2.12.1, BA.4, and BA.5 across all vaccines evaluated. Our data suggest that although Omicron sublineages evade polyclonal neutralizing antibody responses elicited by primary vaccine series, vaccine boosters may provide sufficient protection against Omicron-induced severe disease.
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http://dx.doi.org/10.1126/science.abq0203 | DOI Listing |
NPJ Vaccines
January 2025
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical college, Kunming, China.
The emergence of SARS-CoV-2 variants with defined mutations that enhance pathogenicity or facilitate immune evasion has resulted in a continual decline in the protective efficacy of existing vaccines. Therefore, there is a pressing need for a vaccine capable of combating future variants. In this study, we designed new mRNA vaccines, BSCoV05 and BSCoV06, and generated point mutations in the receptor-binding domain (RBD) of the original Wuhan strain to increase their broad-spectrum antiviral activity.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
Background: Adaptive cellular therapy (ACT), particularly chimeric antigen receptor (CAR)-T cell therapy, has been successful in the treatment of hemopoietic malignancies. However, poor trafficking of administered effector T cells to the tumor poses a great hurdle for this otherwise powerful therapeutic approach in solid cancers. Our previous study revealed that targeting CD93 normalizes tumor vascular functions to improve immune checkpoint blockade therapy.
View Article and Find Full Text PDFDrug Deliv
December 2025
College of Pharmacy, Xinxiang Medical University, Xinxiang, China.
Silicosis represents a formidable occupational lung pathology precipitated by the pulmonary assimilation of respirable crystalline silica particulates. This condition engenders a cascade of cellular oxidative stress via the activation of bioavailable silica, culminating in the generation of reactive oxygen species (ROS). Such oxidative mechanisms lead to irrevocable pulmonary impairment.
View Article and Find Full Text PDFEgypt J Immunol
January 2025
Department of Medical Parasitology, Faculty of Medicine (girls), Al-Azhar University, Cairo, Egypt.
Hepato-intestinal schistosomiasis is characterized by severe pathological changes at advanced chronic stages, including granulomatous lesions and liver fibrosis. The objective of our research was to assess the dynamic expression of profibrotic molecules, the transforming growth factor beta 1 (TGF-β1), and proinflammatory cytokines immunomodulation induced by interleukin 17 (IL-17) neutralization in murine Schistosomiasis mansoni. The study included 56 specific pathogen-free male C57BL/6 mice, divided into 3 main groups: GI uninfected normal controls, GII S.
View Article and Find Full Text PDFIn 2019, diabetes mellitus affected 9.3% of the global population and accounted for one in nine adult deaths. Plant-based antioxidants neutralize harmful free radicals, mitigate oxidative stress, and significantly prevent diabetes and its complications.
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