Hypervariable region 1 (HVR1) is one of the potential neutralization domains in the E2 glycoprotein of hepatitis C virus (HCV). Point mutations of the HVR1 can lead to humoral immune escape in HCV-infected patients. In this study, we segregated the chronically infected viraemic sera from HCV-infected patients into populations of antibody-free virus and antibody-associated virus (AAV) and mapped potential epitopes within the E1E2 gene junction of AAV sequences (residues 364-430). Furthermore, we generated HCV pseudoparticles (HCVpp) derived from AAV sequences to assess their infectivity. We studied the neutralization potential of virus-free Fab obtained from antibody-virus complexes, in the HCVpp system. We observed selective targeting of clonotypic HCV variants from the quasispecies pool. Moreover, we identified potential neutralizing epitopes within the HVR1 and an additional epitope that overlapped with a broadly neutralizing AP33 epitope (amino acid 412-423 in E2). We observed a marked difference in the infectivity of HCVpp generated using E1E2 sequences isolated from AAV. We document reduction in the infectivity of HCVpp-H77 and HCVpp derived from AAV sequences when challenged with virus-free Fab. Our results provide novel insights into the complexities of engagement between HCV and the humoral immune system.
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http://dx.doi.org/10.1099/jgv.0.000659 | DOI Listing |
Front Vet Sci
November 2024
National Animal Disease Center, Agricultural Research Service (USDA), Ames, IA, United States.
The ability to reliably induce bovine digital dermatitis (DD) in naive calves provides unique opportunities to evaluate immune responses of the calves to infection after disease induction, during healing, and after subsequent re-infection. Dairy calves infected in a previous induction trial were held until lesions resolved and were then re-infected in parallel with naïve calves. Humoral and cell-mediated responses were assessed via serum antibody titer and lymphocyte proliferation analysis with responses of previously infected calves compared with responses of the newly infected calves and naïve calves.
View Article and Find Full Text PDFAdv Mater
December 2024
State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
B lymphocytes have emerged as an important immune-regulating target. Inoculation with tumor cell membrane-derived vaccines is a promising strategy to activate B cells, yet their efficiency is limited due to lack of costimulatory molecules. To amplify B cell responses against tumor, herein, a spatiotemporally-synchronized antigen-adjuvant integrated nanovaccine, termed as CM-CpG-aCD40, is constructed by conjugating the immune stimulative CpG oligonucleotide and the anti-CD40 antibody (aCD40) onto the membrane vesicles derived from triple negative breast cancer cells.
View Article and Find Full Text PDFTrends Immunol
December 2024
Immunobiology Laboratory, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland; Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK.
When B cells engage in an immune response, metabolic reprogramming is key to meeting cellular energetic and biosynthetic demands. Epstein-Barr virus (EBV) is a highly prevalent gamma-herpesvirus, latently infecting B cells for the human host's lifetime. By hijacking signaling pathways of T cell-dependent humoral immunity, EBV activates B cells in a T cell-independent manner, forcing lymphoblastoid transformation.
View Article and Find Full Text PDFLancet Microbe
December 2024
Leiden University Center for Infectious Diseases Leiden University Medical Centre, Leiden, Netherlands. Electronic address:
Background: SARS-CoV-2 has been associated with a higher proportion of asymptomatic infections and lower mortality in sub-Saharan Africa than high-income countries. However, there is currently a lack of data on cellular immune responses to SARS-CoV-2 in people living in Africa compared with people in high-income regions of the world. We aimed to assess geographical variation in peripheral and mucosal immune responses.
View Article and Find Full Text PDFCancer Immunol Immunother
December 2024
Department of Clinical Immunology, Medical University of Białystok, Białystok, Poland.
Unlabelled: Vaccination has been considered the most crucial defence against viral infections, including SARS-CoV-2. Numerous reports have demonstrated the effectiveness of the above vaccines in oncological patients. It has also been proven that, apart from vaccinations and oncological therapy, the course of the cancer process itself influences the magnitude of the humoral response, especially in people after infection with SARS-CoV-2.
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