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BioRxiv : the Preprint Server For... Sep 2023Evolution of SARS-CoV-2 requires the reassessment of current vaccine measures. Here, we characterized BA.2.86 and the XBB-lineage variant FLip by investigating their...
Evolution of SARS-CoV-2 requires the reassessment of current vaccine measures. Here, we characterized BA.2.86 and the XBB-lineage variant FLip by investigating their neutralization alongside D614G, BA.1, BA.2, BA.4/5, XBB.1.5, and EG.5.1 by sera from 3-dose vaccinated and bivalent vaccinated healthcare workers, XBB.1.5-wave infected first responders, and monoclonal antibody (mAb) S309. We assessed the biology of the variant Spikes by measuring viral infectivity and membrane fusogenicity. BA.2.86 is less immune evasive compared to FLip and other XBB variants, consistent with antigenic distances. Importantly, distinct from XBB variants, mAb S309 was unable to neutralize BA.2.86, likely due to a D339H mutation based on modeling. BA.2.86 had relatively high fusogenicity and infectivity in CaLu-3 cells but low fusion and infectivity in 293T-ACE2 cells compared to some XBB variants, suggesting a potentially differences conformational stability of BA.2.86 Spike. Overall, our study underscores the importance of SARS-CoV-2 variant surveillance and the need for updated COVID-19 vaccines.
PubMed: 37745517
DOI: 10.1101/2023.09.11.557206 -
International Journal of Molecular... Jul 2023Inflammatory bowel diseases (IBDs) represent chronic idiopathic disorders, including Crohn's disease (CD) and ulcerative colitis (UC), in which one of the trigger... (Review)
Review
Inflammatory bowel diseases (IBDs) represent chronic idiopathic disorders, including Crohn's disease (CD) and ulcerative colitis (UC), in which one of the trigger factors is represented by aberrant immune interactions between the intestinal epithelium and the intestinal microbiota. The involvement of heat shock proteins (HSPs) as etiological and pathogenetic factors is becoming of increasing interest. HSPs were found to be differentially expressed in the intestinal tissues and sera of patients with CD and UC. It has been shown that HSPs can play a dual role in the disease, depending on the stage of progression. They can support the inflammatory and fibrosis process, but they can also act as protective factors during disease progression or before the onset of one of the worst complications of IBD, colorectal cancer. Furthermore, HSPs are able to mediate the interaction between the intestinal microbiota and intestinal epithelial cells. In this work, we discuss the involvement of HSPs in IBD considering their genetic, epigenetic, immune and molecular roles, referring to the most recent works present in the literature. With our review, we want to shed light on the importance of further exploring the role of HSPs, or even better, the role of the molecular chaperone system (CS), in IBD: various molecules of the CS including HSPs may have diagnostic, prognostic and therapeutic potential, promoting the creation of new drugs that could overcome the side-effects of the therapies currently used.
Topics: Humans; Heat-Shock Proteins; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease; Intestines
PubMed: 37569505
DOI: 10.3390/ijms241512129 -
Nature Communications Nov 2023Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in...
Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815-823 adjacent to the fusion peptide, are highly conserved across sarbecoviruses and are recognized by broadly reactive antibodies, providing hope that vaccines targeting these epitopes could offer protection against both current and emergent viruses. Here we employ computational modeling to design scaffolded immunogens that display the spike 815-823 peptide and the stem helix epitopes without the distracting and immunodominant receptor binding domain. These engineered proteins bind with high affinity and specificity to the mature and germline versions of previously identified broadly protective human antibodies. Epitope scaffolds interact with both sera and isolated monoclonal antibodies with broadly reactivity from individuals with pre-existing SARS-CoV-2 immunity. When used as immunogens, epitope scaffolds elicit sera with broad betacoronavirus reactivity and protect as "boosts" against live virus challenge in mice, illustrating their potential as components of a future pancoronavirus vaccine.
Topics: Humans; Animals; Mice; Epitopes; Antibodies, Viral; SARS-CoV-2; Immunodominant Epitopes; Peptides; Spike Glycoprotein, Coronavirus; Antibodies, Neutralizing
PubMed: 38036525
DOI: 10.1038/s41467-023-43638-9 -
The American Journal of Tropical... May 2024
Topics: Humans; Anti-Bacterial Agents; Snake Bites; Antibiotic Prophylaxis; Animals; Antivenins
PubMed: 38507806
DOI: 10.4269/ajtmh.24-0033 -
Communications Biology Sep 2023Canine parvovirus (CPV) is an important pathogen that emerged by cross-species transmission to cause severe disease in dogs. To understand the host immune response to...
Canine parvovirus (CPV) is an important pathogen that emerged by cross-species transmission to cause severe disease in dogs. To understand the host immune response to vaccination, sera from dogs immunized with parvovirus are obtained, the polyclonal antibodies are purified and used to solve the high resolution cryo EM structures of the polyclonal Fab-virus complexes. We use a custom software, Icosahedral Subparticle Extraction and Correlated Classification (ISECC) to perform subparticle analysis and reconstruct polyclonal Fab-virus complexes from two different dogs eight and twelve weeks post vaccination. In the resulting polyclonal Fab-virus complexes there are a total of five distinct Fabs identified. In both cases, any of the five antibodies identified would interfere with receptor binding. This polyclonal mapping approach identifies a specific, limited immune response to the live vaccine virus and allows us to investigate the binding of multiple different antibodies or ligands to virus capsids.
Topics: Animals; Dogs; Parvovirus, Canine; Antibody Formation; Cryoelectron Microscopy; Antibodies; Vaccination
PubMed: 37726539
DOI: 10.1038/s42003-023-05319-7 -
Frontiers in Immunology 2023Transfusion-dependent non-severe aplastic anemia (TD-NSAA) is a rare condition of bone marrow failure that can persist for a long time or develop into severe aplastic...
Transfusion-dependent non-severe aplastic anemia (TD-NSAA) is a rare condition of bone marrow failure that can persist for a long time or develop into severe aplastic anemia (SAA). Little is known about the clinical and laboratory characteristics, and disease prognosis and outcomes in TD-NSAA patients. The clinical and laboratory data of 124 consecutive TD-NSAA patients in the Chinese Eastern Collaboration Group of Anemia from December 2013 and January 2017 were analyzed retrospectively. In 124 TD-NSAA patients, the median age was 32 years (range: 3-80) and the median disease course was 38 months (range: 3-363). Common complications were iron overload (53/101, 52.5%), liver and kidney dysfunction (42/124, 33.9%), diabetes mellitus/impaired glucose tolerance (24/124, 19.4%), and severe infection (29 cases, 23.4%). 58% of patients (57/124) developed severe aplastic anemia with a median progression time of 24 months (range: 3-216). Patients with absolute neutrophil count (ANC) <0.5×10/L, severe infection, or iron overload had a higher probability of progression to SAA (P=0.022, P=0.025, P=0.001). Patients receiving antithymocyte globulin (ATG) plus Cyclosporin A (CsA) had a higher overall response rate compared to those receiving CsA alone (56.7% vs 19.3%, P < 0.001). The addition of ATG was the favorable factor for efficacy (P=0.003). Fourteen patients developed secondary clonal hematologic disease: eleven patients with paroxysmal nocturnal hemoglobinuria, two patients with myelodysplastic syndromes, and one patient with acute myeloid leukemia, respectively. Ten patients (8.1%) died with a median follow-up of 12 months (range: 3- 36 months). Patients with TD-NSAA usually have a prolonged course of disease, and are prone to be complicated with important organ damage and disease progression to SAA. Intensive immunosuppressive therapy based on ATG might be an appropriate approach for TD-NSAA. http://www.chictr.org.cn/edit.aspx?pid=125480&htm=4, identifier ChiCTR2100045895.
Topics: Humans; Adult; Anemia, Aplastic; Retrospective Studies; Cyclosporine; Antilymphocyte Serum; Iron Overload
PubMed: 37497227
DOI: 10.3389/fimmu.2023.1197982 -
Frontiers in Immunology 2023The novel low-dose anti-thymocyte (ATG, 5 mg/kg) plus low-dose post-transplant cyclophosphamide (PTCy, 50 mg/kg) (low-dose ATG/PTCy)-based regimen had promising activity...
Low-dose anti-thymocyte globulin plus low-dose post-transplant cyclophosphamide-based regimen for prevention of graft-versus-host disease after haploidentical peripheral blood stem cell transplants: a large sample, long-term follow-up retrospective study.
INTRODUCTION
The novel low-dose anti-thymocyte (ATG, 5 mg/kg) plus low-dose post-transplant cyclophosphamide (PTCy, 50 mg/kg) (low-dose ATG/PTCy)-based regimen had promising activity for prevention of graft-versus-host disease (GVHD) in haploidentical-peripheral blood stem cell transplantation (haplo-PBSCT), but its impacts on long-term outcomes remain to be defined.
METHODS
We performed a large sample, long-term follow-up retrospective study to evaluate its efficacy for GVHD prophylaxis.
RESULTS
The study enrolled 260 patients, including 162 with myeloid malignancies and 98 with lymphoid malignancies. The median follow-up time was 27.0 months. For the entire cohort, the cumulative incidences (CIs) of grade II-IV and III-IV acute GVHD (aGVHD) by 180 days were 13.46% (95% CI, 9.64%-17.92%) and 5.77% (95% CI, 3.37%-9.07%); while total and moderate/severe chronic GVHD (cGVHD) by 2 years were 30.97% (95% CI, 25.43%-36.66%) and 18.08% (95% CI, 13.68%-22.98%), respectively. The 2-year overall survival (OS), relapse-free survival (RFS), GVHD-free, relapse-free survival (GRFS), non-relapse mortality (NRM), and CIs of relapse were 60.7% (95% CI, 54.8%-67.10%), 58.1% (95% CI, 52.2%-64.5%), 50.6% (95% CI, 44.8-57.1%), 23.04% (95% CI, 18.06%-28.40%), and 18.09% (95% CI, 14.33%-23.97%, respectively. The 1-year CIs of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation were 43.46% (95% CI, 37.39%-49.37%) and 18.08% (95% CI, 13.68%-22.98%), respectively. In multivariate analysis, the disease status at transplantation was associated with inferior survivor outcomes for all patients and myeloid and lymphoid malignancies, while cGVHD had superior outcomes for all patients and myeloid malignancies, but not for lymphoid malignancies.
DISCUSSION
The results demonstrated that the novel regimen could effectively prevent the occurrence of aGVHD in haplo-PBSCT.
Topics: Humans; Antilymphocyte Serum; Peripheral Blood Stem Cell Transplantation; Follow-Up Studies; Retrospective Studies; Hematopoietic Stem Cell Transplantation; Epstein-Barr Virus Infections; Peripheral Blood Stem Cells; Herpesvirus 4, Human; Cyclophosphamide; Graft vs Host Disease; Neoplasms
PubMed: 37954615
DOI: 10.3389/fimmu.2023.1252879 -
Frontiers in Cellular and Infection... 2023Parasitic diseases pose a significant threat to global public health, particularly in developing countries. Host genetic factors play a crucial role in determining... (Review)
Review
Parasitic diseases pose a significant threat to global public health, particularly in developing countries. Host genetic factors play a crucial role in determining susceptibility and resistance to infection. Recent advances in molecular and biological technologies have enabled significant breakthroughs in understanding the impact of host genes on parasite adaptation. In this comprehensive review, we analyze the host genetic factors that influence parasite adaptation, including hormones, nitric oxide, immune cells, cytokine gene polymorphisms, parasite-specific receptors, and metabolites. We also establish an interactive network to better illustrate the complex relationship between host genetic factors and parasite-host adaptation. Additionally, we discuss future directions and collaborative research priorities in the parasite-host adaptation field, including investigating the impact of host genes on the microbiome, developing more sophisticated models, identifying and characterizing parasite-specific receptors, utilizing patient-derived sera as diagnostic and therapeutic tools, and developing novel treatments and management strategies targeting specific host genetic factors. This review highlights the need for a comprehensive and systematic approach to investigating the underlying mechanisms of parasite-host adaptation, which requires interdisciplinary collaborations among biologists, geneticists, immunologists, and clinicians. By deepening our understanding of the complex interactions between host genetics and parasite adaptation, we can develop more effective and targeted interventions to prevent and treat parasitic diseases. Overall, this review provides a valuable resource for researchers and clinicians working in the parasitology field and offers insights into the future directions of this critical research area.
Topics: Humans; Animals; Parasites; Host Adaptation; Cytokines; Microbiota; Nitric Oxide
PubMed: 37637465
DOI: 10.3389/fcimb.2023.1228206 -
Animals : An Open Access Journal From... Aug 2023Bovine herpes virus -1 (BoHV-1) infection leads to upper respiratory tract infection, conjunctivitis and genital disorders in cattle. To control BoHV-1, it is important...
Bovine herpes virus -1 (BoHV-1) infection leads to upper respiratory tract infection, conjunctivitis and genital disorders in cattle. To control BoHV-1, it is important to understand the role of viral proteins in viral infection. BoHV-1 has several gene products to help in viral replication in infected cell. One such gene is deoxyuridine triphosphate nucleotidohydrolase (dUTPase) also known as UL50. In this study, we analyzed the amino acid sequence of UL50 (dUTPase) using bioinformatics tools and found that it was highly conserved among herpesvirus family. Then, it was cloned and expressed in Rosetta (DE3), induced by isopropy1-b-D-thiogalactopyranoside (IPTG) and the recombinant UL50 protein was purified to immunize rabbits for the preparation of polyclonal antiserum. The results indicated that the UL50 gene of BoHV-1 was composed of 978 nucleotides, which encoded 323 amino acids. Western blot analysis revealed that polyclonal sera against UL50 reacted with a band of 34 kDa. Furthermore, immunofluorescence assay showed that UL50 localized in the cytoplasmic area. Taken together, UL50 was successfully cloned, expressed and detected in BoHV-1-infected cells and was localized in the cytoplasm to help in the replication of BoHV-1 in infected cells.
PubMed: 37627398
DOI: 10.3390/ani13162607 -
International Journal of Molecular... Nov 2023In many animals belonging to different taxa, venoms evolved as a means of defense and/or a means of attack/hunting [...].
In many animals belonging to different taxa, venoms evolved as a means of defense and/or a means of attack/hunting [...].
Topics: Animals; Antivenins; Toxins, Biological; Crotalid Venoms
PubMed: 38003582
DOI: 10.3390/ijms242216389