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Calcified Tissue International Aug 2017Paget's disease of bone (PDB) is a common skeletal disorder characterised by focal abnormalities of increased and disorganised bone turnover. Genetic factors play a...
Paget's disease of bone (PDB) is a common skeletal disorder characterised by focal abnormalities of increased and disorganised bone turnover. Genetic factors play a central role in the pathogenesis of PDB but environmental factors also contribute. Measles virus (MV), respiratory syncytial virus (RSV) and canine distemper virus (CDV) have all been implicated as potential disease triggers but the data are conflicting. Since chronic paramyxovirus infection with measles is known to be accompanied by increased production of antiviral antibodies, we have analysed circulating concentrations of antibodies to MV, CDV, and RSV as well as mumps, rubella and varicella zoster virus (VZV) in 463 patients with PDB and 220 aged and gender-matched controls. We also studied the relation between viral antibody concentrations and various markers of disease severity and extent in 460 PDB patients. A high proportion of cases and controls tested positive for antiviral antibodies but there was no significant difference in circulating antibody concentrations between PDB cases and controls for MV, CDV, RSV, rubella or VZV. However, mumps virus antibody levels were significantly higher in the PDB cases (mean ± SD = 3.1 ± 0.84 vs. 2.62 ± 0.86. p < 0.001). There was no association between disease severity and circulating antibody concentrations to any of the viruses. In conclusion, we found no evidence to suggest that PDB is associated with abnormalities of immune response to measles or other paramyxoviruses, although there was evidence of a greater antibody response to mumps. The results do not support that hypothesis that PDB is associated with a persistent infection with measles or other paramyxoviruses.
Topics: Aged; Aged, 80 and over; Antibody Formation; Bone and Bones; Female; Humans; In Situ Hybridization; Male; Middle Aged; Osteitis Deformans; Osteoclasts; Paramyxovirinae
PubMed: 28361207
DOI: 10.1007/s00223-017-0265-4 -
Frontiers in Immunology 2019Vaccines play a vital role in protecting our communities against infectious disease. Unfortunately, some vaccines provide only partial protection or in some cases... (Review)
Review
Vaccines play a vital role in protecting our communities against infectious disease. Unfortunately, some vaccines provide only partial protection or in some cases vaccine-mediated immunity may wane rapidly, resulting in either increased susceptibility to that disease or a requirement for more booster vaccinations in order to maintain immunity above a protective level. The durability of antibody responses after infection or vaccination appears to be intrinsically determined by the structural biology of the antigen, with multivalent protein antigens often providing more long-lived immunity than monovalent antigens. This forms the basis for the Imprinted Lifespan model describing the differential survival of long-lived plasma cell populations. There are, however, exceptions to this rule with examples of highly attenuated live virus vaccines that are rapidly cleared and elicit only short-lived immunity despite the expression of multivalent surface epitopes. These exceptions have led to the concept that multivalency alone may not reliably determine the duration of protective humoral immune responses unless a minimum number of long-lived plasma cells are generated by reaching an appropriate antigenic threshold of B cell stimulation. Examples of long-term and in some cases, potentially lifelong antibody responses following immunization against human papilloma virus (HPV), Japanese encephalitis virus (JEV), Hepatitis B virus (HBV), and Hepatitis A virus (HAV) provide several lessons in understanding durable serological memory in human subjects. Moreover, studies involving influenza vaccination provide the unique opportunity to compare the durability of hemagglutinin (HA)-specific antibody titers mounted in response to antigenically repetitive whole virus (i.e., multivalent HA), or detergent-disrupted "split" virus, in comparison to the long-term immune responses induced by natural influenza infection. Here, we discuss the underlying mechanisms that may be associated with the induction of protective immunity by long-lived plasma cells and their importance in future vaccine design.
Topics: Antibody Formation; Humans; Immunologic Memory; Vaccines
PubMed: 31118935
DOI: 10.3389/fimmu.2019.00956 -
Science Translational Medicine Dec 2015With an emphasis on systems analyses, the VSV-EBOVAC project harnesses state-of-the-art technologies that illuminate mechanisms behind the observed immunogenicity and... (Review)
Review
With an emphasis on systems analyses, the VSV-EBOVAC project harnesses state-of-the-art technologies that illuminate mechanisms behind the observed immunogenicity and reactogenicity of the rVSV-ZEBOV vaccine and ensures that such information is shared among stakeholders.
Topics: Antibody Formation; Clinical Trials as Topic; Ebola Vaccines; Ebolavirus; Humans; Knowledge; Research; Vaccination
PubMed: 26659569
DOI: 10.1126/scitranslmed.aad3106 -
Cell Reports. Medicine Mar 2024Subvariants of the Omicron lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) efficiently escape neutralizing antibody responses induced by both...
Subvariants of the Omicron lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) efficiently escape neutralizing antibody responses induced by both vaccination and infection with antigenically distinct variants. Here, we describe the potency and breadth of neutralizing and binding antibody responses against a large panel of variants following an Omicron BA.1 or BA.2 breakthrough infection in a heterogeneous cohort of individuals with diverse exposure histories. Both BA.1 and BA.2 breakthrough infections significantly boost antibody levels and broaden antibody reactivity. However, this broader immunity induced by BA.1 and BA.2 breakthrough infections does not neutralize Omicron BQ and XBB subvariants efficiently. While these subvariants are not neutralized well by post-breakthrough sera, suggesting escape, binding non-neutralizing antibody responses are sustained. In summary, our data suggest that while BA.1 and BA.2 breakthrough infections broaden the immune response to SARS-CoV-2 spike, the induced neutralizing antibody response is still outpaced by viral evolution.
Topics: Humans; Antibody Formation; Breakthrough Infections; COVID-19; SARS-CoV-2; Antibodies, Neutralizing
PubMed: 38508136
DOI: 10.1016/j.xcrm.2024.101474 -
Proceedings. Biological Sciences Nov 2020The transfer of antibodies from mother to offspring provides crucial protection against infection to offspring during early life in humans and domestic and laboratory...
The transfer of antibodies from mother to offspring provides crucial protection against infection to offspring during early life in humans and domestic and laboratory animals. However, few studies have tested the consequences of variation in maternal antibody transfer for offspring fitness in the wild. Further, separating the immunoprotective effects of antibodies from their association with nutritional resources provided by mothers is difficult. Here, we measured plasma levels of total and parasite-specific antibodies in neonatal (less than 10 days old) wild Soay sheep over 25 years to quantify variation in maternal antibody transfer and test its association with offspring survival. Maternal antibody transfer was predicted by maternal age and previous antibody responses, and was consistent within mothers across years. Neonatal total IgG antibody levels were positively related to early growth, suggesting they reflected nutritional transfer. Neonatal parasite-specific IgG levels positively predicted first-year survival, independent of lamb weight, total IgG levels and subsequent lamb parasite-specific antibody levels. This relationship was partly mediated via an indirect negative association with parasite burden. We show that among-female variation in maternal antibody transfer can have long-term effects on offspring growth, parasite burden and fitness in the wild, and is likely to impact naturally occurring host-parasite dynamics.
Topics: Animals; Animals, Wild; Antibody Formation; Female; Helminths; Immunoglobulin G; Mammals; Sheep
PubMed: 33234082
DOI: 10.1098/rspb.2020.1931 -
Frontiers in Immunology 2023
Topics: Antibody Formation; Immune System Diseases
PubMed: 38077378
DOI: 10.3389/fimmu.2023.1335217 -
Frontiers in Immunology 2020The development of anti-drug antibodies (ADAs) is a common cause for treatment failure and hypersensitivity reactions for many biologics. The focus of this review is the... (Review)
Review
The development of anti-drug antibodies (ADAs) is a common cause for treatment failure and hypersensitivity reactions for many biologics. The focus of this review is the development of ImmTOR, a platform technology designed to prevent the formation of ADAs that can be applied broadly across a wide variety of biologics by inducing immunological tolerance with ImmTOR nanoparticles encapsulating rapamycin. The induction of tolerance is antigen-specific and dependent on the incorporation of rapamycin in nanoparticles and the presence of the antigen at the time of administration of ImmTOR. Evidence for the induction of specific immune tolerance vs. general immune suppression is supported by the findings that: (1) ImmTOR induces regulatory T cells specific to the co-administered antigen; (2) tolerance can be transferred by adoptive transfer of splenocytes from treated animals to naïve recipients; (3) the tolerance is durable to subsequent challenge with antigen alone; and (4) animals tolerized to a specific antigen are capable of responding to an unrelated antigen. ImmTOR nanoparticles can be added to new or existing biologics without the need to modify or reformulate the biologic drug. The ability of ImmTOR to mitigate the formation of ADAs has been demonstrated for coagulation factor VIII in a mouse model of hemophilia A, an anti-TNFα monoclonal antibody in a mouse model of inflammatory arthritis, pegylated uricase in hyperuricemic mice and in non-human primates, acid alpha-glucosidase in a mouse model of Pompe disease, recombinant immunotoxin in a mouse model of mesothelioma, and adeno-associated vectors in a model of repeat dosing of gene therapy vectors in mice and in non-human primates. Human proof-of concept for the mitigation of ADAs has been demonstrated with SEL-212, a combination product consisting of ImmTOR + pegadricase, a highly immunogenic enzyme therapy for the treatment of gout. ImmTOR represents a promising approach to preventing the formation of ADAs to a broad range of biologic drugs.
Topics: Animals; Antibodies; Antibody Formation; Biological Products; Drug Compounding; Humans; Immune Tolerance; Immunosuppressive Agents; Lactates; Nanomedicine; Nanoparticles; Polyesters; Polyethylene Glycols; Sirolimus
PubMed: 32508839
DOI: 10.3389/fimmu.2020.00969 -
Aging Jul 2019Antibody responses to vaccinations or infections decline upon aging. In this study we tested if metabolic changes in B cells may contribute to attenuation of responses... (Comparative Study)
Comparative Study
Antibody responses to vaccinations or infections decline upon aging. In this study we tested if metabolic changes in B cells may contribute to attenuation of responses to influenza vaccination in aged humans. Our data show that aging affects mitochondrial functions in B cells leading to increases in mitochondrial reactive oxygen species (MROS) and mitochondrial mass (MM) in some aged B cell subsets and decreases in expression levels of Sirtuin 1 (SIRT1), Forkhead box protein (FOX)O1 and carnitine palmitoyltransferase 1 (CPT-1). Seahorse analyses showed minor defects in glycolysis in the aged B cells after activation but a strong reduction in oxidative phosphorylation. The analyses of the transcriptome revealed further pronounced defects in one-carbon metabolism, a pathway that is essential for amino acid and nucleotide metabolism. Overall our data support the notion that the declining ability of aged B cells to increase their metabolism following activation contributes to the weakened antibody responses of the elderly.
Topics: Adult; Aged; Aged, 80 and over; Aging; Antibody Formation; B-Lymphocytes; Energy Metabolism; Female; Humans; Male
PubMed: 31283526
DOI: 10.18632/aging.102058 -
Clinical Cancer Research : An Official... Nov 2021The role of B cells in the tumor microenvironment and B-cell-mediated antitumor immune responses remains relatively understudied. Recent seminal studies have discovered... (Review)
Review
The role of B cells in the tumor microenvironment and B-cell-mediated antitumor immune responses remains relatively understudied. Recent seminal studies have discovered that B cells and associated tertiary lymphoid structures correlate with responses to checkpoint blockade immunotherapy and are prognostic for overall survival of cancer patients. B-cell subsets have remarkable functional diversity and include professional antigen-presenting cells, regulatory cells, memory populations, and antibody-producing plasma cells. Importantly, secreted antibodies can independently activate innate immune responses and induce the cancer immunity cycle. Thus, B cells and B-cell-mediated antibody responses comprise the largely underappreciated second arm of the adaptive immune system and certainly deserve further attention in the field of oncology. Here, we review the known functions of B cells in the tumor microenvironment, the contribution of B cells to the antitumor activity of immunotherapies, and the role of B cells in the overall survival of cancer patients.
Topics: Animals; Antibody Formation; Antigen-Presenting Cells; B-Lymphocytes; Biomarkers; Disease Management; Humans; Immune Checkpoint Inhibitors; Immunomodulation; Lymphopoiesis; Molecular Targeted Therapy; Neoplasms; Prognosis; Treatment Outcome; Tumor Microenvironment
PubMed: 34230025
DOI: 10.1158/1078-0432.CCR-21-0697 -
Postepy Higieny I Medycyny... Apr 2016Monoclonal antibodies (mAbs) are biomolecules of great scientific and practical significance. In contrast to polyclonal antibodies from immune sera, they are homogeneous... (Review)
Review
Monoclonal antibodies (mAbs) are biomolecules of great scientific and practical significance. In contrast to polyclonal antibodies from immune sera, they are homogeneous and monospecific, since they are produced by hybridoma cells representing a clone arising from a single cell. The successful technology was described for the first time in 1975; the inventors were later awarded the Nobel Prize. Currently, mAbs are broadly used as a research tool, in diagnostics and medicine in particular for the treatment of cancer or in transplantology. About 47 therapeutics based on monoclonal antibodies are now available in the US and Europe, and the number is still growing. Production of monoclonal antibodies is a multistage, time-consuming and costly process. Growing demand for these molecules creates space for research focused on improvements in hybridoma technology. Lower costs, human labor, and time are important goals of these attempts. In this article, a brief review of current methods and their advances is given.
Topics: Antibodies, Monoclonal; Antibody Formation; Antibody-Producing Cells; Europe; Humans; Hybridomas; Neoplasms
PubMed: 27117113
DOI: 10.5604/17322693.1200552