Antibodies最新文献

{"title":"A Physiologically Based Pharmacokinetic Model Relates the Subcutaneous Bioavailability of Monoclonal Antibodies to the Saturation of FcRn-Mediated Recycling in Injection-Site-Draining Lymph Nodes.","authors":"Felix Stader, Cong Liu, Abdallah Derbalah, Hiroshi Momiji, Xian Pan, Iain Gardner, Masoud Jamei, Armin Sepp","doi":"10.3390/antib13030070","DOIUrl":"10.3390/antib13030070","url":null,"abstract":"<p><p>The bioavailability of a monoclonal antibody (mAb) or another therapeutic protein after subcutaneous (SC) dosing is challenging to predict from first principles, even if the impact of injection site physiology and drug properties on mAb bioavailability is generally understood. We used a physiologically based pharmacokinetic model to predict pre-systemic clearance after SC administration mechanistically by incorporating the FcRn salvage pathway in antigen-presenting cells (APCs) in peripheral lymph nodes, draining the injection site. Clinically observed data of the removal rate of IgG from the arm as well as its plasma concentration after SC dosing were mostly predicted within the 95% confidence interval. The bioavailability of IgG was predicted to be 70%, which mechanistically relates to macropinocytosis in the draining lymph nodes and transient local dose-dependent partial saturation of the FcRn receptor in the APCs, resulting in higher catabolism and consequently less drug reaching the systemic circulation. The predicted free FcRn concentration was reduced to 40-45%, reaching the minimum 1-2 days after the SC administration of IgG, and returned to baseline after 8-12 days, depending on the site of injection. The model predicted the uptake into APCs, the binding affinity to FcRn, and the dose to be important factors impacting the bioavailability of a mAb.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamics of IgM and IgG Antibody Response Profile against Linear B-Cell Epitopes from Exoerythrocytic (CelTOS and TRAP) and Erythrocytic (CyRPA) Phases of <i>Plasmodium vivax</i>: Follow-Up Study.","authors":"Cinthia Magalhães Rodolphi, Isabela Ferreira Soares, Ada da Silva Matos, Rodrigo Nunes Rodrigues-da-Silva, Marcelo Urbano Ferreira, Lilian Rose Pratt-Riccio, Paulo Renato Rivas Totino, Kézia Katiani Gorza Scopel, Josué da Costa Lima-Junior","doi":"10.3390/antib13030069","DOIUrl":"10.3390/antib13030069","url":null,"abstract":"<p><p>Malaria is a serious health problem worldwide affecting mainly children and socially vulnerable people. The biological particularities of <i>P. vivax</i>, such as the ability to generate dormant liver stages, the rapid maturation of gametocytes, and the emergence of drug resistance, have contributed to difficulties in disease control. In this context, developing an effective vaccine has been considered a fundamental tool for the efficient control and/or elimination of vivax malaria. Although recombinant proteins have been the main strategy used in designing vaccine prototypes, synthetic immunogenic peptides have emerged as a viable alternative for this purpose. Considering, therefore, that in the Brazilian endemic population, little is known about the profile of the humoral immune response directed to synthetic peptides that represent different <i>P. vivax</i> proteins, the present work aimed to map the epitope-specific antibodies' profiles to synthetic peptides representing the linear portions of the ookinete and sporozoite cell passage protein (CelTOS), thrombospondin-related adhesive protein (TRAP), and cysteine-rich protective antigen (CyRPA) proteins in the acute (AC) and convalescent phases (Conv30 and Conv180 after infection) of vivax malaria. The results showed that the studied subjects responded to all proteins for at least six months following infection. For IgM, a few individuals (3-21%) were positive during the acute phase of the disease; the highest frequencies were observed for IgG (28-57%). Regarding the subclasses, IgG2 and IgG3 stood out as the most prevalent for all peptides. During the follow-up, the stability of IgG was observed for all peptides. Only one significant positive correlation was observed between IgM and exposure time. We conclude that for all the peptides, the immunodominant epitopes are recognized in the exposed population, with similar frequency and magnitude. However, if the antibodies detected in this study are potential protectors, this needs to be investigated.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Monoclonal Antibody Specific toward Amyloid-β Binds to a Unique Epitope within the N-Terminal Region","authors":"Giavanna Paterno, Brenda D. Moore, Brach M. Bell, Kimberly-Marie M. Gorion, Yong Ran, Stefan Prokop, Todd E. Golde, Benoit I Giasson","doi":"10.3390/antib13030068","DOIUrl":"https://doi.org/10.3390/antib13030068","url":null,"abstract":"Amyloid-β (Aβ) deposition throughout the neuroaxis is a classical hallmark of several neurodegenerative diseases, most notably Alzheimer’s disease (AD). Aβ peptides of varied length and diverse structural conformations are deposited within the parenchyma and vasculature in the brains of individuals with AD. Neuropathologically, Aβ pathology can be assessed using antibodies to label and characterize their features, which in turn leads to a more extensive understanding of the pathological process. In the present study, we generated a novel monoclonal antibody, which we found to be specific for the N-terminal region of Aβ. This antibody reacted to amyloid precursor protein expressed in cultured cells and labels Aβ plaques and cerebral amyloid angiopathy in brain tissue from a mouse model of amyloidosis as well as post-mortem brain tissue from patients diagnosed with AD. This highly specific novel antibody will serve as a unique tool for future studies investigating Aβ deposition in novel mouse models and cross-sectional studies using post-mortem human tissue.","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141924176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Conserved Linear Epitopes on Viral Protein 2 of Foot-and-Mouth Disease Virus Serotype O by Monoclonal Antibodies 6F4.D11.B6 and 8D6.B9.C3.","authors":"Wantanee Tommeurd, Kanyarat Thueng-In, Sirin Theerawatanasirikul, Nongnaput Tuyapala, Sukontip Poonsuk, Nantawan Petcharat, Nattarat Thangthamniyom, Porntippa Lekcharoensuk","doi":"10.3390/antib13030067","DOIUrl":"10.3390/antib13030067","url":null,"abstract":"<p><p>Foot-and-mouth disease (FMD) is a highly infectious disease of cloven-hoofed animals with a significant economic impact. Early diagnosis and effective prevention and control could reduce the spread of the disease which could possibly minimize economic losses. Epitope characterization based on monoclonal antibodies provide essential information for developing diagnostic assays and vaccine designs. In this study, monoclonal antibodies raised against FMD virus (FMDV) were produced. Sixty-six monoclonal antibodies demonstrated strong reactivity and specificity to FMDV. The purified monoclonal antibodies were further used for bio-panning to select phage expressing specific epitopes from phage-displayed 12 mer-peptide library. The phage peptide sequences were analyzed using multiple sequence alignment and evaluated by peptide ELISA. Two hybridoma clones secreted monoclonal antibodies recognizing linear epitopes on VP2 of FMDV serotype O. The non-neutralizing monoclonal antibody 6F4.D11.B6 recognized the residues 67-78 on antigenic site 2 resinding in VP2, while the neutralizing monoclonal antibody 8D6.B9.C3 recognized a novel linear epitope encompassing residues 115-126 on VP2. This information and the FMDV-specific monoclonal antibodies provide valuable sources for further study and application in diagnosis, therapeutics and vaccine designs to strengthen the disease prevention and control measures.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced N-Glycan Profiling of Therapeutic Monoclonal Antibodies through the Application of Upper-Hinge Middle-Up Level LC-HRMS Analysis.","authors":"Natalia Mesonzhnik, Anton Belushenko, Polina Novikova, Alexey Kukharenko, Mikhail Afonin","doi":"10.3390/antib13030066","DOIUrl":"10.3390/antib13030066","url":null,"abstract":"<p><p>Therapeutic monoclonal antibodies (mAbs) are crucial in modern medicine due to their effectiveness in treating various diseases. However, the structural complexity of mAbs, particularly their glycosylation patterns, presents challenges for quality control and biosimilarity assessment. This study explores the use of upper-hinge middle-up (UHMU)-level ultra-high-performance liquid chromatography-high-resolution mass spectrometry (LC-HRMS) analysis to improve N-glycan profiling of mAbs. Two specific enzymes, known as IgG degradation enzymes (IGDEs), were used to selectively cleave therapeutic mAbs above the hinge region to separate antibody subunits for further Fc glycan analysis by means of the UHMU/LC-HRMS workflow. The complexity of the mass spectra of IGDEs-digested mAbs was significantly reduced compared to the intact MS level, enabling reliable assignment and relative quantitation of paired Fc glycoforms. The results of the UHMU/LC-HRMS analysis of nine approved therapeutics highlight the significance of this approach for in-depth glycoform profiling.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Seraph 100^® Microbind Affinity Blood Filter Does Not Alter Levels of Circulating or Mucosal Antibodies in Critical COVID-19 Patients.","authors":"Tonia L Conner, Pooja Vir, Eric D Laing, Ian J Stewart, Edward Mitre, Kathleen P Pratt","doi":"10.3390/antib13030065","DOIUrl":"10.3390/antib13030065","url":null,"abstract":"<p><p>PURIFY-OBS-1 is an observational study evaluating the safety and efficacy of Seraph 100^® Microbind Affinity Blood Filter (Seraph 100) use for COVID-19 patients with respiratory failure admitted to the intensive care unit (ICU). The Seraph 100 is a hemoperfusion device containing heparin-coated beads that can bind to, and reduce levels of, some circulating pathogens and inflammatory molecules. This study evaluated whether treatment with the Seraph 100 affected circulating and mucosal antibody levels in critically ill COVID-19 subjects. SARS-CoV-2 anti-spike and anti-nucleocapsid IgG and IgA levels in serum were evaluated at enrollment and on days 1, 4, 7, and 28 after Seraph 100 application, while anti-spike and nucleocapsid IgG, IgA, and secretory IgA levels in tracheal aspirates were evaluated at enrollment and on days 1, 2, 3, 7, and 28. Serum samples were also collected from the pre- and post-filter lines at 1 and 4 h following Seraph 100 application to evaluate the direct impact of the filter on circulating antibody levels. Treatment with the Seraph 100 did not alter the levels of circulating or mucosal antibodies in critically ill COVID-19 subjects admitted to the ICU.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knowledge of the Serological Response to the Third BNT162b2 Vaccination May Influence Compliance of Healthcare Workers to Booster Dose.","authors":"Avi Magid, Khetam Hussein, Halima Dabaja-Younis, Moran Szwarcwort-Cohen, Ronit Almog, Michal Mekel, Avi Weissman, Gila Hyams, Vardit Gepstein, Netanel A Horowitz, Hagar Cohen Saban, Jalal Tarabeia, Michael Halberthal, Yael Shachor-Meyouhas","doi":"10.3390/antib13030063","DOIUrl":"10.3390/antib13030063","url":null,"abstract":"<p><strong>Background: </strong>Previous studies showed that the fourth SARS-CoV-2 vaccine dose has a protective effect against infection, as well as against severe disease and death. This study aimed to examine whether knowledge of a high-level antibody after the third dose may reduce compliance to the fourth booster dose among healthcare workers (HCWs).</p><p><strong>Methods: </strong>We conducted a prospective cohort study among HCWs vaccinated with the first three doses at Rambam Healthcare Campus, a tertiary hospital in northern Israel. Participants underwent a serological test before the fourth booster vaccine was offered to all of them, with results provided to participants. The population was divided into two groups, namely those with antibodies below 955 AU/mL and those with 955 AU/mL and higher, a cutoff found protective in a previous study. Multiple logistic regression was carried out to compare the compliance to the fourth booster between the two groups, adjusted for demographic and clinical variables.</p><p><strong>Results: </strong>After adjusting for the confounding variables, the compliance was higher in those with antibody levels below 955 AU/mL (OR = 1.41, <i>p</i> = 0.05, 95% CI 1.10-1.96). In addition, male sex and age of 60 years and above were also associated with higher vaccination rates (OR = 2.28, <i>p</i> < 0.001, 95% CI 1.64-3.17), (OR = 1.14, <i>p</i> = 0.043, 95% CI 1.06-1.75), respectively.</p><p><strong>Conclusions: </strong>Knowledge of the antibody status may affect compliance with the booster dose. Considering waning immunity over time, reduced compliance may affect the protection of HCWs who declined the fourth dose.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Flow Cytometry Method Detecting Complement C1q Bound to Blood Type A/B IgG Antibody for Preventing Severe Antibody-Mediated Rejection in ABO-Incompatible Kidney Transplantation.","authors":"Tsutomu Ishizuka, Kazuhiro Iwadoh, Hiroshi Kataoka, Junichi Hoshino, Kosaku Nitta, Hideki Ishida","doi":"10.3390/antib13030062","DOIUrl":"10.3390/antib13030062","url":null,"abstract":"<p><p>We aimed to develop a novel method for measuring the complement-binding ability of anti-blood type antibodies (ab-Abs), the flow cytometry method for the complement C1q test (FCM-C1q) for detecting antibody-mediated rejection (AMR) caused by ab-Abs in ABO-incompatible kidney transplantation (ABOI-KTx). FCM-C1q distribution was surveyed in 44 healthy participants and 43 dialysis patients (Cohort A). The relationship between AMR and FCM-C1q levels was examined along with ab-Ab titers by the flow cytometry method for the IgG test (FCM-IgG) in 62 ABOI-KTx patients (Cohort B). FCM-IgG and C1q levels were significantly higher in type O participants than in A/B participants in Cohort A. There were minimal differences in the distribution of FCM-IgG and C1q between dialysis and healthy participants. Sixteen cases were suspected of acute rejections (ARs) in Cohort B, of whom nine had AR clinically. One patient with severe AMR was highly suspected of hyperacute rejection along with another patient with severe AMR. Their postoperative FCM-C1q and FCM-IgG levels were elevated. Another two patients showed high FCM-IgG and C1q levels before KTx, and these levels remained low after KTx with no or mild rejection. In conclusion, our results suggest that a high positivity rate for FCM-C1q may predict moderate to severe AMR caused by ab-Abs and poor prognosis in ABOI-KTx.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevention of Blood Incompatibility Related Hemagglutination: Blocking of Antigen A on Red Blood Cells Using <i>In Silico</i> Designed Recombinant Anti-A scFv.","authors":"Saleha Hafeez, Najam Us Sahar Sadaf Zaidi","doi":"10.3390/antib13030064","DOIUrl":"10.3390/antib13030064","url":null,"abstract":"<p><p>Critical blood shortages plague healthcare systems, particularly in lower-income and middle-income countries. This affects patients requiring regular transfusions and creates challenges during emergencies where universal blood is vital. To address these shortages and support blood banks during emergencies, this study reports a method for increasing the compatibility of blood group A red blood cells (RBCs) by blocking surface antigen-A using anti-A single chain fragment variable (scFv). To enhance stability, the scFv was first modified with the addition of interdomain disulfide bonds. The most effective location for this modification was found to be H44-L232 of mutant-1a scFv. ScFv was then produced from <i>E.coli</i> BL21(DE3) and purified using a three-step process. Purified scFvs were then used to block maximum number of antigens-A on RBCs, and it was found that only monomers were functional, while dimers formed through incorrect domain-swapping were non-functional. These antigen-blocked RBCs displayed no clumping in hemagglutination testing with incompatible blood plasma. The dissociation constant K_D was found to be 0.724 μM. Antigen-blocked RBCs have the potential to be given to other blood groups during emergencies. This innovative approach could significantly increase the pool of usable blood, potentially saving countless lives.</p>","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogeneic HLA Humoral Immunogenicity and the Prediction of Donor-Specific HLA Antibody Development","authors":"Vadim Jucaud","doi":"10.3390/antib13030061","DOIUrl":"https://doi.org/10.3390/antib13030061","url":null,"abstract":"The development of de novo donor-specific HLA antibodies (dnDSAs) following solid organ transplantation is considered a major risk factor for poor long-term allograft outcomes. The prediction of dnDSA development is a boon to transplant recipients, yet the assessment of allo-HLA immunogenicity remains imprecise. Despite the recent technological advances, a comprehensive evaluation of allo-HLA immunogenicity, which includes both B and T cell allorecognition, is still warranted. Recent studies have proposed using mismatched HLA epitopes (antibody and T cell) as a prognostic biomarker for humoral alloimmunity. However, the identification of immunogenic HLA mismatches has not progressed despite significant improvements in the identification of permissible mismatches. Certainly, the prediction of dnDSA development may benefit permissible HLA mismatched organ transplantations, personalized immunosuppression, and clinical trial design. However, characteristics that go beyond the listing of mismatched HLA antibody epitopes and T cell epitopes, such as the generation of HLA T cell epitope repertoires, recipient’s HLA class II phenotype, and immunosuppressive regiments, are required for the precise assessment of allo-HLA immunogenicity.","PeriodicalId":8188,"journal":{"name":"Antibodies","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141807117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}