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Nature Immunology Dec 2022Systems vaccinology has defined molecular signatures and mechanisms of immunity to vaccination. However, comparative analysis of immunity to different vaccines is...
Systems vaccinology has defined molecular signatures and mechanisms of immunity to vaccination. However, comparative analysis of immunity to different vaccines is lacking. We integrated transcriptional data of over 3,000 samples, from 820 adults across 28 studies of 13 vaccines and analyzed vaccination-induced signatures of antibody responses. Most vaccines induced signatures of innate immunity and plasmablasts at days 1 and 7, respectively, after vaccination. However, the yellow fever vaccine induced an early transient signature of T and B cell activation at day 1, followed by delayed antiviral/interferon and plasmablast signatures that peaked at days 7 and 14-21, respectively. Thus, there was no evidence for a 'universal signature' that predicted antibody response to all vaccines. However, accounting for the asynchronous nature of responses, we defined a time-adjusted signature that predicted antibody responses across vaccines. These results provide a transcriptional atlas of immunity to vaccination and define a common, time-adjusted signature of antibody responses.
Topics: Adult; Humans; Antibody Formation; Gene Expression Profiling; Vaccines; Vaccination; Immunity, Innate; Antibodies, Viral
PubMed: 36316475
DOI: 10.1038/s41590-022-01328-6 -
International Journal of Molecular... Aug 2020A functional adaptive immune response is the major determinant for clearance of hepatitis C virus (HCV) infection. However, in the majority of patients, this response... (Review)
Review
A functional adaptive immune response is the major determinant for clearance of hepatitis C virus (HCV) infection. However, in the majority of patients, this response fails and persistent infection evolves. Here, we dissect the HCV-specific key players of adaptive immunity, namely B cells and T cells, and describe factors that affect infection outcome. Once chronic infection is established, continuous exposure to HCV antigens affects functionality, phenotype, transcriptional program, metabolism, and the epigenetics of the adaptive immune cells. In addition, viral escape mutations contribute to the failure of adaptive antiviral immunity. Direct-acting antivirals (DAA) can mediate HCV clearance in almost all patients with chronic HCV infection, however, defects in adaptive immune cell populations remain, only limited functional memory is obtained and reinfection of cured individuals is possible. Thus, to avoid potential reinfection and achieve global elimination of HCV infections, a prophylactic vaccine is needed. Recent vaccine trials could induce HCV-specific immunity but failed to protect from persistent infection. Thus, lessons from natural protection from persistent infection, DAA-mediated cure, and non-protective vaccination trials might lead the way to successful vaccination strategies in the future.
Topics: Adaptive Immunity; Animals; Antibody Formation; Clinical Trials as Topic; Hepacivirus; Humans; T-Lymphocytes; Viral Vaccines
PubMed: 32781731
DOI: 10.3390/ijms21165644 -
Trends in Immunology Sep 2015Activation-induced cytidine deaminase (AID) mediates cytosine deamination and underlies two central processes in antibody diversification: somatic hypermutation and... (Review)
Review
Activation-induced cytidine deaminase (AID) mediates cytosine deamination and underlies two central processes in antibody diversification: somatic hypermutation and class-switch recombination. AID deamination is not exclusive to immunoglobulin loci; it can instigate DNA lesions in non-immunoglobulin genes and thus stringent checks are in place to constrain and restrict its activity. Recent findings have provided new insights into the mechanisms that target AID activity to specific genomic regions, revealing an involvement for noncoding RNAs associated with polymerase pausing and with enhancer transcription as well as genomic architecture. We review these findings and integrate them into a model for multilevel regulation of AID expression and targeting in immunoglobulin and non-immunoglobulin loci. Within this framework we discuss gaps in understanding, and outline important areas of further research.
Topics: Animals; Antibody Formation; Cytidine Deaminase; Gene Expression Regulation; Genetic Loci; Humans; Immunoglobulin Class Switching; Immunoglobulins; Protein Binding; Protein Interaction Domains and Motifs; Transcription Factors
PubMed: 26254147
DOI: 10.1016/j.it.2015.07.003 -
Viruses May 2023Infectious diseases represent one of the major public health concerns on the global level [...].
Infectious diseases represent one of the major public health concerns on the global level [...].
Topics: Antibody Formation; RNA Viruses; Public Health
PubMed: 37243299
DOI: 10.3390/v15051214 -
The Journal of Experimental Medicine May 2017Tissue adaptation is an intrinsic component of immune cell development, influencing both resistance to pathogens and tolerance. Chronically stimulated surfaces of the... (Review)
Review
Tissue adaptation is an intrinsic component of immune cell development, influencing both resistance to pathogens and tolerance. Chronically stimulated surfaces of the body, in particular the gut mucosa, are the major sites where immune cells traffic and reside. Their adaptation to these environments requires constant discrimination between natural stimulation coming from harmless microbiota and food, and pathogens that need to be cleared. This review will focus on the adaptation of lymphocytes to the gut mucosa, a highly specialized environment that can help us understand the plasticity of leukocytes arriving at various tissue sites and how tissue-related factors operate to shape immune cell fate and function.
Topics: Adaptation, Physiological; Animals; Antibody Formation; Humans; Immune Tolerance; Intestinal Mucosa; Lymphocytes; T-Lymphocytes, Regulatory
PubMed: 28432200
DOI: 10.1084/jem.20162014 -
Oncoimmunology 2022
Topics: Animals; Antibody Formation; Ferroptosis; Marsupialia
PubMed: 36185805
DOI: 10.1080/2162402X.2022.2127273 -
Frontiers in Immunology 2020Improving understanding of the bovine adaptive immune response would equip researchers to more efficiently design interventions against pathogens that impact upon food... (Review)
Review
Improving understanding of the bovine adaptive immune response would equip researchers to more efficiently design interventions against pathogens that impact upon food security and animal welfare. There are features of the bovine antibody response that differ substantially from other mammalian species, including the best understood models in the human and mouse. These include the ability to generate a functionally diverse immunoglobulin response despite having a fraction of the germline gene diversity that underpins this process in humans and mice, and the unique structure of a subset of immunoglobulins with "ultralong" HCDR3 domains, which are of significant interest with respect to potential therapeutics, including against human pathogens. However, a more detailed understanding of the B cell response and the production of an effective antibody response in the bovine is currently hampered by the lack of reagents for the B cell lineage. In this article we outline the current state of knowledge and capabilities with regard to B cell and antibody responses in cattle, highlight resource gaps, and summarize recent advances that have the potential to fundamentally advance our understanding of this process in the bovine host.
Topics: Animals; Antibody Formation; B-Lymphocytes; Cattle
PubMed: 32595642
DOI: 10.3389/fimmu.2020.01175 -
Physiological Reviews Jan 1965
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Pharmaceutical Research Jun 2009Injectable drug delivery systems (DDS) such as particulate carriers and water-soluble polymers are being used and developed for a wide variety of therapeutic... (Review)
Review
Injectable drug delivery systems (DDS) such as particulate carriers and water-soluble polymers are being used and developed for a wide variety of therapeutic applications. However, a number of immunological risks with serious clinical implications are associated with administration of DDS. These immunological events can compromise the efficacy and safety of these systems by changing the pharmacokinetics, biodistribution and targeting capability of DDS, and by inducing hypersensitivity reactions. Antibodies induced by administration of DDS can be directed against the carrier material, the drug and/or targeting ligands associated with the DDS. Complement activation and opsonization of DDS, which may or may not be associated with antibody formation, may lead to accelerated clearance, hypersensitivity reactions and formation of membrane attack complexes resulting in premature release of the drug. Also platelets have been reported to play a role in DDS immunogenicity. Despite our curtailed understanding of the relationships between physicochemical characteristics and immunogenicity of DDS, several risk factors have been identified. Insight into these factors should be employed in the development of novel DDS with low immunological risk.
Topics: Animals; Antibody Formation; Complement Activation; Drug Carriers; Drug Hypersensitivity; Humans; Injections; Platelet Activation
PubMed: 19247815
DOI: 10.1007/s11095-009-9855-9 -
Cellular Immunology Dec 2022Protein based therapeutics have successfully improved the quality of life for patients of monogenic disorders like hemophilia, Pompe and Fabry disease. However, a... (Review)
Review
Protein based therapeutics have successfully improved the quality of life for patients of monogenic disorders like hemophilia, Pompe and Fabry disease. However, a significant proportion of patients develop immune responses towards intravenously infused therapeutic protein, which can complicate or neutralize treatment and compromise patient safety. Strategies aimed at circumventing immune responses following therapeutic protein infusion can greatly improve therapeutic efficacy. In recent years, antigen-based oral tolerance induction has shown promising results in the prevention and treatment of autoimmune diseases, food allergies and can prevent anti-drug antibody formation to protein replacement therapies. Oral tolerance exploits regulatory mechanisms that are initiated in the gut associated lymphoid tissue (GALT) to promote active suppression of orally ingested antigen. In this review, we outline general perceptions and current knowledge about the mechanisms of oral tolerance, including tissue specific sites of tolerance induction and the cells involved, with emphasis on antigen presenting cells and regulatory T cells. We define several factors, such as cytokines and metabolites that impact the stability and expansion potential of these immune modulatory cells. We highlight preclinical studies that have been performed to induce oral tolerance to therapeutic proteins or enzymes for single gene disorders, such as hemophilia or Pompe disease. These studies mainly utilize a transgenic plant-based system for oral delivery of antigen in conjugation with fusion protein technology that favors the prevention of antigen degradation in the stomach while enhancing uptake in the small intestine by antigen presenting cells and regulatory T cell induction, thereby promoting antigen specific systemic tolerance.
Topics: Humans; Hemophilia A; Antibody Formation; Quality of Life; Enzyme Replacement Therapy; Antibodies
PubMed: 36402002
DOI: 10.1016/j.cellimm.2022.104641