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PloS One 2024Art v4.01 is a well-known profilin protein belonging to the pan-allergens group and is commonly involved in triggering allergic asthma, polyallergy, and...
Art v4.01 is a well-known profilin protein belonging to the pan-allergens group and is commonly involved in triggering allergic asthma, polyallergy, and cross-sensitization. It is also referred to as Wormwood due to its origin. Crude wormwood extracts are applied for allergen-specific immunotherapy (AIT). Whether the recombinant Art v4.01 (rArt v4.01) can produce in vivo immunological tolerance by subcutaneous immunotherapy (SCIT) remains elusive. In this study, to investigate the in vivo immunological response of rArt v4.01, Th2, Th1, Treg, Th17 type-related cytokines and phenotypes of immune cells were tested, facilitating the exploration of the underlying mechanisms. The expression and purification of Art v4.01 were carried out using recombinant techniques. Allergic asthma female BALB/c mice were induced by subcutaneous sensitization of wormwood pollen extract and intranasal challenges. SCIT without adjuvant was performed using the rArt v4.01 and wormwood pollen extract for 2 weeks. Following exposure to challenges, the levels of immunoglobulin E (IgE), cytokines, and inflammatory cells were assessed through enzyme-linked immunosorbent assay (ELISA) and histological examination of sera, bronchoalveolar lavage fluid (BALF), and lung tissue. These parameters were subsequently compared between treatment groups receiving rArt v4.01 and wormwood pollen extract. The rArt v4.01 protein was expressed, which had a high purity (>90%) and an allergenic potency. Compared with the pollen extract, rArt v4.01 was superior in terms of reducing the number of white blood cells (WBCs), total nucleated cells (TNCs), and monocytes (MNs) in BALF and the degree of lung inflammation (1.77±0.99 vs. 2.31±0.80, P > 0.05). Compared with the model group, only rArt v4.01 reduced serum IgE level (1.19±0.25 vs. 1.61±0.17 μg/ml, P = 0.062), as well as the levels of Th2 type-related cytokines (interleukin-4 (IL-4) (107.18±16.17 vs. 132.47±20.85 pg/ml, P < 0.05) and IL-2 (19.52±1.19 vs. 24.02±2.14 pg/ml, P < 0.05)). The study suggested that rArt v4.01 was superior to pollen extract in reducing the number of inflammatory cells in BALF, pneumonitis, levels of pro-inflammatory cytokines, and serum IgE level. These findings confirmed that Art v4.01 could be a potential candidate protein for allergen-specific immunotherapy.
Topics: Animals; Female; Asthma; Mice; Mice, Inbred BALB C; Disease Models, Animal; Immune Tolerance; Recombinant Proteins; Cytokines; Immunoglobulin E; Pollen; Desensitization, Immunologic; Allergens; Profilins; Bronchoalveolar Lavage Fluid; Injections, Subcutaneous
PubMed: 38941291
DOI: 10.1371/journal.pone.0280418 -
PloS One 2024Hepatitis C virus (HCV) infection remains a major cause of liver related morbidity and mortality worldwide. Epidemiologic data on seroprevalence, viremia prevalence and...
Hepatitis C virus (HCV) infection remains a major cause of liver related morbidity and mortality worldwide. Epidemiologic data on seroprevalence, viremia prevalence and risk factors remain limited in sub-Saharan Africa. In Ghana, HCV-related deaths are estimated to have increased since 2015. Risk factors associated with HCV infection in Ghana are not well described. The aim of this study was to determine the prevalence of, and risk factors associated with hepatitis C virus infection in the Upper East Region located in the northern part of Ghana. A community-based cross-sectional study was conducted in 9 communities in the Upper East region of Ghana. A total of 1,769 participants aged ≥12 years were screened for HCV antibody (anti-HCV) using rapid diagnostic testing (RDT). Seventy-four participants undertook HCV RNA testing after a positive anti-HCV result. Multivariate logistic regression was used to determine risk factors associated with HCV seropositivity. The anti-HCV prevalence was 8.4%, with 149 out of 1,769 testing anti-HCV positive. Mean age (±SD) of seropositive persons was 45.4 (±16.3) years. The highest anti-HCV seroprevalence was amongst persons aged 60 years and above. Forty-four out of 74 (59.5%) seropositive cases had viremic infection and the estimated viremic prevalence in the screened population was 5.0%. Predictors of HCV seropositivity were age (OR 1.03 95% CI 1.01-1.04), history of female genital mutilation or circumcision (OR 1.63 95% CI 1.04-2.55), sexual activity (OR 2.57 95% CI 1.38-4.79), positive maternal HCV status (OR 10.38 95% CI 4.13-26.05) and positive HIV status (OR 4.03 95% CI 1.35-12.05). In conclusion, the Upper East Region demonstrates a high Hepatitis C antibody prevalence. Almost 60% of individuals have viremic infection, however the cost of RNA testing is a barrier to virological diagnosis. There is a need to educate the population about HCV-associated risk factors to reduce HCV transmission and burden of disease.
Topics: Humans; Ghana; Female; Male; Middle Aged; Cross-Sectional Studies; Risk Factors; Adult; Hepatitis C; Prevalence; Hepacivirus; Young Adult; Seroepidemiologic Studies; Adolescent; Hepatitis C Antibodies; Aged; Child
PubMed: 38941280
DOI: 10.1371/journal.pone.0306292 -
Clinical and Experimental Medicine Jun 2024Both atezolizumab (a PD-L1 inhibitor) plus bevacizumab (A+B) and sintilimab (a PD-1 inhibitor) plus bevacizumab (S+B) are recommended as the first-line regimen for... (Comparative Study)
Comparative Study
Both atezolizumab (a PD-L1 inhibitor) plus bevacizumab (A+B) and sintilimab (a PD-1 inhibitor) plus bevacizumab (S+B) are recommended as the first-line regimen for advanced hepatocellular carcinoma (HCC) in China. Different efficacy between the two regimens combined with transvascular intervention for unresectable HCC (uHCC) remain unknown. We retrospectively analyzed uHCC patients treated in three centers by simultaneous combination of A+B or S+B with transarterial chemoembolization (TACE) and FOLFOX-based hepatic arterial infusion chemotherapy (HAIC). Objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAEs) were compared. Totally 188 patients were included, with 92 and 96 administered A+B+TACE-HAIC (ABTH) and S+B+TACE-HAIC (SBTH), respectively. ORRs (62.0 vs. 70.8%, respectively; P = 0.257) and disease control rates (88.0 vs. 93.8%, P = 0.267) were similar between groups by the mRECIST criteria. ABTH showed no survival advantage over SBTH, with median PFS times of 11.7 months and 13.0 months, respectively (HR = 0.81, 95% CI, 0.52-1.26, P = 0.35) and similar OS times (HR = 1.19, 95% CI, 0.32-4.39, P = 0.8). No significant differences were observed in grade 3-4 TRAEs between groups. Either PD-L1 or PD-1 inhibitor plus bevacizumab combined with TACE-HAIC have similarly excellent therapeutic efficacy with manageable adverse events, representing promising treatment options for uHCC.
Topics: Humans; Carcinoma, Hepatocellular; Male; Bevacizumab; Middle Aged; Female; Liver Neoplasms; Retrospective Studies; Aged; Antineoplastic Combined Chemotherapy Protocols; Adult; Antibodies, Monoclonal, Humanized; Treatment Outcome; Immune Checkpoint Inhibitors; China; Chemoembolization, Therapeutic; Programmed Cell Death 1 Receptor; B7-H1 Antigen; Fluorouracil; Leucovorin
PubMed: 38940944
DOI: 10.1007/s10238-024-01415-y -
Microbiology Spectrum Jun 2024We used phage display, antibody engineering, and high-throughput assays to identify antibody-accessible targets of . We report the discovery of monoclonal antibodies...
We used phage display, antibody engineering, and high-throughput assays to identify antibody-accessible targets of . We report the discovery of monoclonal antibodies (mAbs) binding to type 3 fimbrial proteins, including MrkA. We found that anti-MrkA mAbs were cross-reactive to a diverse panel of clinical isolates, representing different O-serotypes. mAbs binding to MrkA have previously been described and have been shown to provide prophylactic protection, although only modest protection when dosed therapeutically in a murine lung infection model. Here, we used a combination of binding and opsonophagocytic killing studies using a high-content imaging platform to provide a possible explanation for the modest therapeutic efficacy reported in that model. Our work shows that expression of type 3 fimbriae in culture is not homogenous within a bacterial population. Instead, sub-populations of bacteria that do, and do not, express type 3 fimbriae exist. In a high-content opsonophagocytic killing assay, we showed that MrkA-targeting antibodies initially promote killing by macrophages; however, over time, this effect is diminished. We hypothesize the reason for this is that bacteria not expressing MrkA can evade opsonophagocytosis. Our data support the fact that MrkA is a conserved, immunodominant protein that is antibody accessible on the surface of and suggest that additional studies should evaluate the potential of using anti-MrkA antibodies in different stages of infection (different sites in the body) as well as against biofilms in the body during infection and associated with medical devices.IMPORTANCEThere is an unmet, urgent need for the development of novel antimicrobial therapies for the treatment of infections. We describe the use of phage display, antibody engineering, and high-throughput assays to identify antibody-accessible targets of . We discovered monoclonal antibodies (mAbs) binding to the type 3 fimbrial protein MrkA. The anti-MrkA mAbs were found to be highly cross-reactive, binding to all strains tested from a diverse panel of clinical isolates, and were active in an opsonophagocytic killing assay at pM concentrations. MrkA is important for biofilm formation; thus, our data support further exploration of the use of anti-MrkA antibodies for preventing and/or controlling in biofilms and during infection.
PubMed: 38940542
DOI: 10.1128/spectrum.00400-24 -
Frontiers in Bioscience (Landmark... Jun 2024The treatment options for multiple myeloma (MM) have undergone significant transformation with the advent of immunotherapy. Novel therapies that focus on tumor antigens... (Review)
Review
The treatment options for multiple myeloma (MM) have undergone significant transformation with the advent of immunotherapy. Novel therapies that focus on tumor antigens now drive advances in MM research. Bispecific antibodies (bsAbs) leverage revolutionary advances in bioengineering techniques and embody the second generation of antibody-based tumor therapy. Recent studies on bsAbs in relapsed/refractory MM cases have revealed remarkable efficacy and acceptable safety profiles. The approval of elranatamab and teclistamab represents the next step in the development of bsAbs for the treatment of MM. This review article addresses the antigen targeting, efficacy, safety, and strategies in the application of bsAbs against treatment-resistant MM, with a focus on clinical trials and real-world data.
Topics: Multiple Myeloma; Antibodies, Bispecific; Humans; Immunotherapy; Antigens, Neoplasm; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological
PubMed: 38940040
DOI: 10.31083/j.fbl2906216 -
Euro Surveillance : Bulletin Europeen... Jun 2024BackgroundSince its emergence in December 2019, over 700 million people worldwide have been infected with SARS-CoV-2 up to May 2024. While early rollout of mRNA...
A longitudinal study on SARS-CoV-2 seroconversion, reinfection and neutralisation spanning several variant waves and vaccination campaigns, Heinsberg, Germany, April 2020 to November 2022.
BackgroundSince its emergence in December 2019, over 700 million people worldwide have been infected with SARS-CoV-2 up to May 2024. While early rollout of mRNA vaccines against COVID-19 has saved many lives, there was increasing immune escape of new virus variants. Longitudinal monitoring of population-wide SARS-CoV-2 antibody responses from regular sample collection irrespective of symptoms provides representative data on infection and seroconversion/seroreversion rates.AimTo examine adaptive and cellular immune responses of a German SARS-CoV-2 outbreak cohort through several waves of infection with different virus variants.MethodsUtilising a 31-month longitudinal seroepidemiological study (n = 1,446; mean age: 50 years, range: 2-103) initiated during the first SARS-CoV-2 superspreading event (February 2020) in Heinsberg, Germany, we analysed acute infection, seroconversion and virus neutralisation at five follow-up visits between October 2020 and November 2022; cellular and cross-protective immunity against SARS-CoV-2 Omicron variants were also examined.ResultsSARS-CoV-2 spike (S)-specific IgAs decreased shortly after infection, while IgGs remained stable. Both increased significantly after vaccination. We predict an 18-month half-life of S IgGs upon infection. Nucleocapsid (N)-specific responses declined over 12 months post-infection but increased (p < 0.0001) during Omicron. Frequencies of SARS-CoV-2-specific TNF-alpha+/IFN-gamma+ CD4+ T-cells declined over 12 months after infection (p < 0.01). SARS-CoV-2 S antibodies and neutralisation titres were highest in triple-vaccinated participants infected between April 2021 and November 2022 compared with infections between April 2020 and January 2021. Cross neutralisation against Omicron BQ.1.18 and XBB.1.5 was very low in all groups.ConclusionInfection and/or vaccination did not provide the population with cross-protection against Omicron variants.
Topics: Humans; SARS-CoV-2; COVID-19; Seroconversion; Longitudinal Studies; Germany; Antibodies, Viral; Middle Aged; Adult; Male; Antibodies, Neutralizing; Female; COVID-19 Vaccines; Aged; Reinfection; Seroepidemiologic Studies; Adolescent; Young Adult; Child; Child, Preschool; Aged, 80 and over; Vaccination
PubMed: 38940003
DOI: 10.2807/1560-7917.ES.2024.29.26.2300659 -
Exploration (Beijing, China) Jun 2024Protein-based drugs have shown unique advantages to treat various diseases in recent years. However, most protein therapeutics in clinical use are limited to...
Protein-based drugs have shown unique advantages to treat various diseases in recent years. However, most protein therapeutics in clinical use are limited to extracellular targets with low delivery efficiency. To realize targeted protein delivery, a series of stimuli-triggered nanoparticle formulations have been developed to improve delivery efficiency and reduce off-target release. These smart nanoparticles are designed to release cargo proteins in response to either internal or external stimuli at pathological tissues. In this way, varieties of protein-based drugs including antibodies, enzymes, and pro-apoptotic proteins can be effectively delivered to desired sites for the treatment of cancer, inflammation, metabolic diseases, and so on with minimal side effects. In this review, recent advances in the design of stimuli-triggered nanomedicine for targeted protein delivery in different biomedical applications will be discussed. A deeper understanding of these emerging strategies helps develop more efficient protein delivery systems for clinical use in the future.
PubMed: 38939867
DOI: 10.1002/EXP.20230025 -
Journal of Immunology Research 2024Vaccination is one of the most effective prophylactic public health interventions for the prevention of infectious diseases such as coronavirus disease (COVID-19).... (Review)
Review
Vaccination is one of the most effective prophylactic public health interventions for the prevention of infectious diseases such as coronavirus disease (COVID-19). Considering the ongoing need for new COVID-19 vaccines, it is crucial to modify our approach and incorporate more conserved regions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to effectively address emerging viral variants. The nucleocapsid protein is a structural protein of SARS-CoV-2 that is involved in replication and immune responses. Furthermore, this protein offers significant advantages owing to the minimal accumulation of mutations over time and the inclusion of key T-cell epitopes critical for SARS-CoV-2 immunity. A novel strategy that may be suitable for the new generation of vaccines against COVID-19 is to use a combination of antigens, including the spike and nucleocapsid proteins, to elicit robust humoral and potent cellular immune responses, along with long-lasting immunity. The strategic use of multiple antigens aims to enhance vaccine efficacy and broaden protection against viruses, including their variants. The immune response against the nucleocapsid protein from other coronavirus is long-lasting, and it can persist up to 11 years post-infection. Thus, the incorporation of nucleocapsids (N) into vaccine design adds an important dimension to vaccination efforts and holds promise for bolstering the ability to combat COVID-19 effectively. In this review, we summarize the preclinical studies that evaluated the use of the nucleocapsid protein as antigen. This study discusses the use of nucleocapsid alone and its combination with spike protein or other proteins of SARS-CoV-2.
Topics: Humans; COVID-19 Vaccines; SARS-CoV-2; COVID-19; Coronavirus Nucleocapsid Proteins; Immunogenicity, Vaccine; Animals; Phosphoproteins; Spike Glycoprotein, Coronavirus; Epitopes, T-Lymphocyte; Antibodies, Viral; Nucleocapsid Proteins
PubMed: 38939745
DOI: 10.1155/2024/9313267 -
Journal of Extracellular Biology Mar 2024Extracellular vesicles (EVs) are intensively investigated for their therapeutic potential and application as drug delivery vehicle. A broad perception of favourable...
Extracellular vesicles (EVs) are intensively investigated for their therapeutic potential and application as drug delivery vehicle. A broad perception of favourable safety profiles and low immunogenicity make EVs an attractive alternative to synthetic nanoparticles. We recently showed that repeated intravenous administration of human cell-derived EVs into pig-tailed macaques unexpectedly elicited antibody responses after three or more injections. This coincided with decreasing EV circulation time, and may thus hamper successful EV-mediated cargo delivery into tissues. Here, we share the custom ELISA protocol that we used to measure such antibody responses. This protocol may help other researchers evaluate immune responses to EV-based therapies in preclinical studies.
PubMed: 38939411
DOI: 10.1002/jex2.129 -
Cureus May 2024Membranous nephropathy (MN) is a significant cause of nephrotic syndrome in non-diabetic adults. It can be primary, attributed to autoantibodies targeting podocyte...
Membranous nephropathy (MN) is a significant cause of nephrotic syndrome in non-diabetic adults. It can be primary, attributed to autoantibodies targeting podocyte antigens, or secondary to various disorders. Although rare, nerve epidermal growth factor-like 1 (NELL-1)-associated MN presents diagnostic and management challenges. Thrombotic complications such as renal vein thrombosis (RVT) are recognized but less reported, especially in NELL-1-positive MN. We report a 43-year-old male with NELL-1-positive MN complicated by acute kidney injury (AKI) due to bilateral RVT, treated successfully with thrombolysis. Histopathological analysis confirmed MN with specific immunohistochemical staining for NELL-1. Treatment included immunosuppressive therapy and tailored anticoagulation. This case emphasizes recognizing thrombotic complications in MN, particularly in NELL-1-positive cases. Further research is needed to explore serum anti-NELL-1 antibodies as biomarkers and optimal anticoagulation strategies in MN patients at risk of thrombotic events to improve outcomes and guide personalized management.
PubMed: 38939287
DOI: 10.7759/cureus.61230