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Frontiers in Immunology 2024Immune responses to both SARS-CoV-2 infection and its associated vaccines have been highly variable within the general population. The increasing evidence of... (Review)
Review
Immune responses to both SARS-CoV-2 infection and its associated vaccines have been highly variable within the general population. The increasing evidence of long-lasting symptoms after resolution of infection, called post-acute sequelae of COVID-19 (PASC) or "Long COVID," suggests that immune-mediated mechanisms are at play. Closely related endemic common human coronaviruses (hCoV) can induce pre-existing and potentially cross-reactive immunity, which can then affect primary SARS-CoV-2 infection, as well as vaccination responses. The influence of pre-existing immunity from these hCoVs, as well as responses generated from original CoV2 strains or vaccines on the development of new high-affinity responses to CoV2 antigenic viral variants, needs to be better understood given the need for continuous vaccine adaptation and application in the population. Due in part to thymic involution, normal aging is associated with reduced naïve T cell compartments and impaired primary antigen responsiveness, resulting in a reliance on the pre-existing cross-reactive memory cell pool which may be of lower affinity, restricted in diversity, or of shorter duration. These effects can also be mediated by the presence of down-regulatory anti-idiotype responses which also increase in aging. Given the tremendous heterogeneity of clinical data, utilization of preclinical models offers the greatest ability to assess immune responses under a controlled setting. These models should now involve prior antigen/viral exposure combined with incorporation of modifying factors such as age on immune responses and effects. This will also allow for mechanistic dissection and understanding of the different immune pathways involved in both SARS-CoV-2 pathogen and potential vaccine responses over time and how pre-existing memory responses, including potential anti-idiotype responses, can affect efficacy as well as potential off-target effects in different tissues as well as modeling PASC.
Topics: Humans; COVID-19; Post-Acute COVID-19 Syndrome; SARS-CoV-2; Vaccines; Aging; Immunoglobulin Idiotypes
PubMed: 38469293
DOI: 10.3389/fimmu.2024.1345499 -
Clinical and Experimental Vaccine... Jan 2024Since the 1950s decade, it has been suggested that a naturally produced or induced repertoire of immunoglobulin G (IgG) idiotypes may exert some immunoregulatory... (Review)
Review
Immune modulation and possible pathological implications mediated by naturally produced immunoglobulin G idiotypes: from historical to recent experimental and clinical studies focused on atopic dermatitis.
Since the 1950s decade, it has been suggested that a naturally produced or induced repertoire of immunoglobulin G (IgG) idiotypes may exert some immunoregulatory functions. In the last decades, some more advanced theories have suggested that the repertoire of IgG idiotypes may influence the development or control of some atopic diseases. In atopic dermatitis (AD), some evidence indicated that the IgG repertoire obtained from these patients could effectively mediate regulatory functions on thymic and peripheral CD4+ and CD8+ T cells. Furthermore, some recent clinical trials have corroborated the hypothesis that IgG from AD patients can exert regulatory functions . Here, we revised some historical aspects that yield current approaches developed and to elucidate a recently proposed theory termed "hooks without bait" that can strengthen the broad spectrum of research about evaluating different sets of IgG idiotypes and determine their immunological effects.
PubMed: 38362367
DOI: 10.7774/cevr.2024.13.1.1 -
Blood Advances Feb 2024
Topics: Humans; Neoplasm, Residual; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Immunoglobulins; High-Throughput Nucleotide Sequencing
PubMed: 38147627
DOI: 10.1182/bloodadvances.2023011997 -
Frontiers in Immunology 2023The regulatory T (Treg) cells constitute a functionally defined subpopulation of T cells that modulate the immune system and maintain immune tolerance through... (Review)
Review
The regulatory T (Treg) cells constitute a functionally defined subpopulation of T cells that modulate the immune system and maintain immune tolerance through suppression of the development of autoimmune responses to self-antigens and allergic reactions to external antigens. Reduction in the number or function of Treg cells has been suggested as a key immune abnormality underlying the development of autoimmune and allergic diseases. studies have demonstrated that purified polyvalent immunoglobulin G (IgG) from multiple healthy blood donors can exert immunomodulatory effects on Treg cells. Incubation of polyvalent human IgG with purified CD4CD25 T cells increased the intracellular expression of interleukin (IL)-10. Intravenous administration of polyvalent human IgG induced significant expansions of CD4 Foxp3 Treg cells and clinical improvements in patients with autoimmune diseases. In human clinical trials, intramuscular administration of autologous total IgG significantly increased the percentage of IL-10-producing CD4 Treg cells in the peripheral blood of healthy subjects and provided significant clinical improvements in patients with atopic dermatitis. These results suggest a clinical usefulness of polyvalent IgG-induced activation of Treg cells in human subjects. This review proposes a new hypothesis for immune tolerance mechanism by integrating the pre-existing "idiotypic network theory" and "Treg cell theory" into an "anti-idiotypic Treg cell theory." Based on this hypothesis, an "active anti-idiotypic therapy" for allergic and autoimmune diseases using autologous polyvalent IgG (as immunizing antigens) is suggested as follows: (1) Intramuscular or subcutaneous administration of autologous polyvalent IgG produces numerous immunogenic peptides derived from idiotypes of autologous IgG through processing of dendritic cells, and these peptides activate anti-idiotypic Treg cells in the same subject. (2) Activated anti-idiotypic Treg cells secrete IL-10 and suppress Th2 cell response to allergens and autoimmune T cell response to self-antigens. (3) These events can induce a long-term clinical improvements in patients with allergic and autoimmune diseases. Further studies are needed to evaluate the detailed molecular mechanism underlying polyvalent IgG-induced Treg cell activation and the clinical usefulness of this immunomodulatory therapy for autoimmune and allergic diseases.
Topics: Humans; T-Lymphocytes, Regulatory; Interleukin-10; Immunoglobulin G; Immune Tolerance; Allergens; Hypersensitivity; Autoimmune Diseases; Autoantigens
PubMed: 38094290
DOI: 10.3389/fimmu.2023.1242860 -
Bioinformation 2022The CoViD-19 pandemic has demonstrated the need for future developments in anti-viral immunology. We propose that artificial intelligence (AI) and machine learning, and...
The CoViD-19 pandemic has demonstrated the need for future developments in anti-viral immunology. We propose that artificial intelligence (AI) and machine learning, and in particular fractal analysis could play a crucial role in that context. Fractals - never-ending repeats of self-similar shapes whose composite tend to resemble the whole - are found in most natural biological structures including immunoglobulin and antigenic epitopes. Increased knowledge of the fractalomic properties of the idiotype/anti-idiotypic paradigm should help develop a novel and improved simplified artificial model of the immune system. Case in point, the regulation and dampening of antibodies as well as the synergetic recognition of an antigen by multiple idiotypes are both immune mechanisms that require further analysis. An enhanced understanding of these complexities could lead to better data analysis for novel vaccines to improve their sensitivity and specificity as well as open other new doors in the field of immunology.
PubMed: 37426493
DOI: 10.6026/97320630018730 -
Viruses May 2023T-cell recognition of antigen epitopes is a crucial step for the induction of adaptive immune responses, and the identification of such T-cell epitopes is, therefore,...
T-cell recognition of antigen epitopes is a crucial step for the induction of adaptive immune responses, and the identification of such T-cell epitopes is, therefore, important for understanding diverse immune responses and controlling T-cell immunity. A number of bioinformatic tools exist that predict T-cell epitopes; however, many of these methods highly rely on evaluating conventional peptide presentation by major histocompatibility complex (MHC) molecules, but they ignore epitope sequences recognized by T-cell receptor (TCR). Immunogenic determinant idiotopes are present on the variable regions of immunoglobulin molecules expressed on and secreted by B-cells. In idiotope-driven T-cell/B-cell collaboration, B-cells present the idiotopes on MHC molecules for recognition by idiotope-specific T-cells. According to the idiotype network theory formulated by Niels Jerne, such idiotopes found on anti-idiotypic antibodies exhibit molecular mimicry of antigens. Here, by combining these concepts and defining the patterns of TCR-recognized epitope motifs (TREMs), we developed a T-cell epitope prediction method that identifies T-cell epitopes derived from antigen proteins by analyzing B-cell receptor (BCR) sequences. This method allowed us to identify T-cell epitopes that contain the same TREM patterns between BCR and viral antigen sequences in two different infectious diseases caused by dengue virus and SARS-CoV-2 infection. The identified epitopes were among the T-cell epitopes detected in previous studies, and T-cell stimulatory immunogenicity was confirmed. Thus, our data support this method as a powerful tool for the discovery of T-cell epitopes from BCR sequences.
Topics: Humans; T-Lymphocytes; Epitopes, T-Lymphocyte; Epitopes, B-Lymphocyte; COVID-19; SARS-CoV-2; Receptors, Antigen, T-Cell; Receptors, Antigen, B-Cell
PubMed: 37243272
DOI: 10.3390/v15051186 -
Allergy, Asthma & Immunology Research Jan 2023Immunoglobulin E (IgE)-mediated egg allergy presents as one of the most common food allergies. The level of specific IgE (sIgE) antibody is widely used as an important...
Immunoglobulin E (IgE)-mediated egg allergy presents as one of the most common food allergies. The level of specific IgE (sIgE) antibody is widely used as an important diagnostic indicator. However, sIgE antibody levels are often inconsistent with the clinical manifestations of patients. The heterogeneity of egg-specific IgE idiotypes (sIgE-IDs) may help reflect clinical egg allergy severity. Eight peptides were synthesized, corresponding to the linear epitopes of ovomucoid (OVM). The sIgE-IDs of egg-allergic patients were detected by enzyme-linked immunosorbent assay. Fresh peripheral blood was collected from patients with different heterogeneity strength of sIgE-ID, and egg extract was used as a stimulus to the basophil activation test (BAT). RBL-2H3 cells were sensitized with serum with different strength of sIgE-ID heterogeneity and the release rate of β-hexosaminidase was calculated. Among 75 patients with egg allergy, 24% had sIgE for all epitopes and 85% had sIgE for at least one epitope. Analysis of individual patients revealed differences in epitope recognition patterns among the patients, that is, heterogeneity in sIgE-ID. More importantly, the number of IgE-positive peptides had a strong correlation with allergic symptoms in egg-allergic patients ( = 0.706). BAT and RBL-2H3 cell degranulation confirmed that higher sIgE-ID heterogeneity strength was more effective in inducing effector cell responses. Our results suggest that the greater the heterogeneity strength of OVM-sIgE-ID, the more severe the allergic symptoms.
PubMed: 36693362
DOI: 10.4168/aair.2023.15.1.109 -
MAbs 2022ADA Anti-Drug Antibodies; BCR B Cell Receptor; BId Idiotype-specific B Cell; BiTE Bispecific T cell Engager; BMC Bone Marrow Chimeric Mice; BSA Bovine Serum Albumin; CDR...
ADA Anti-Drug Antibodies; BCR B Cell Receptor; BId Idiotype-specific B Cell; BiTE Bispecific T cell Engager; BMC Bone Marrow Chimeric Mice; BSA Bovine Serum Albumin; CDR Complementary Determining Region; CEA Carcinoembryonic Antigen; CIT Cancer Immunotherapy; CitAbs Cancer Immunotherapy Antibodies; DC Dendritic Cell; ELISA Enzyme-Linked Immunosorbent Assay; FcRn Neonatal Fc Receptor; FcyR Fc gamma Receptor; GM-CSF Granulocyte-Macrophage Colony Stimulating Factor; gMFI Geometric Mean Fluorescence Intensity; H Heavy Chain; IC Immune Complex; Id Idiotype; IgA Immunoglobulin alpha; IgG1 Immunoglobulin gamma 1; IL-2 Interleukin 2; IL-2R Interleukin 2 Receptor; IL2v Interleukin 2 Variant; IVIG1 Intravenous Immunoglobulin 1; KLH Keyhole Limpet Hemocyanin; L Light Chain; MAPPs MHC-associated Peptide Proteomics; MHC Major Histocompatibility Complex; PBMC Peripheral Blood Mononuclear Cells; PBS Phosphate Buffered Saline; SHM Somatic Hypermutation; scFv Single-chain Variable Fragment; TCR T cell Receptor; TFc Fc-specific T cell; TId Id-specific T cell; UV Ultraviolet; V Variable.
Topics: Humans; Mice; Animals; Immunoglobulin G; Interleukin-2; Mice, Transgenic; Leukocytes, Mononuclear; Immunotherapy; Neoplasms
PubMed: 36394299
DOI: 10.1080/19420862.2022.2143009 -
Frontiers in Immunology 2022Guillain-Barré syndrome (GBS) is an autoimmune neurological disorder often preceded by viral illnesses or, more rarely, vaccinations. We report on a unique combination...
Guillain-Barré syndrome (GBS) is an autoimmune neurological disorder often preceded by viral illnesses or, more rarely, vaccinations. We report on a unique combination of postcoronavirus disease 2019 (COVID-19) vaccine GBS that occurred months after a parainfectious COVID-19-related GBS. Shortly after manifesting COVID-19 symptoms, a 57-year-old man developed diplopia, right-side facial weakness, and gait instability that, together with electrophysiology and cerebrospinal fluid examinations, led to a diagnosis of post-COVID-19 GBS. The involvement of cranial nerves and IgM seropositivity for ganglioside GD1b were noteworthy. COVID-19 pneumonia, flaccid tetraparesis, and autonomic dysfunction prompted his admission to ICU. He recovered after therapy with intravenous immunoglobulins (IVIg). Six months later, GBS recurred shortly after the first dose of the Pfizer/BioNTech vaccine. Again, the GBS diagnosis was confirmed by cerebrospinal fluid and electrophysiology studies. IgM seropositivity extended to multiple gangliosides, namely for GM3/4, GD1a/b, and GT1b IgM. An IVIg course prompted complete recovery. This case adds to other previously reported observations suggesting a possible causal link between SARS-CoV-2 and GBS. Molecular mimicry and anti-idiotype antibodies might be the underlying mechanisms. Future COVID-19 vaccinations/revaccinations in patients with previous para-/post-COVID-19 GBS deserve a reappraisal, especially if they are seropositive for ganglioside antibodies.
Topics: Autoantibodies; COVID-19; COVID-19 Vaccines; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin M; Immunoglobulins, Intravenous; Male; Middle Aged; SARS-CoV-2
PubMed: 35924236
DOI: 10.3389/fimmu.2022.894872 -
Neoantigens - the next frontier in precision immunotherapy for B-cell lymphoproliferative disorders.Blood Reviews Nov 2022Broad activation of host T-cell immunity by immune checkpoint blockade, has revolutionized the treatment of some but not all B-cell lymphoproliferative disorders (LPDs).... (Review)
Review
Broad activation of host T-cell immunity by immune checkpoint blockade, has revolutionized the treatment of some but not all B-cell lymphoproliferative disorders (LPDs). The challenge for next generation immunotherapeutics, is to successfully induce anti-tumor specific T-cell immunity across a range of B-LPDs, without provoking immune-related adverse events. An emerging strategy is to target neoantigens. Neoantigens are immunogenic peptides, unique to malignant cells, that are presented to T-cells via human leukocyte antigens. Neoantigens most commonly arise from non-synonymous mutations but can also be derived from tumor specific alterations along the protein biosynthesis pathway. B-cell LPDs uniquely express a clonal B-cell receptor (BCR) idiotype, consisting of immunoglobulin genes that undergo recombination and somatic hypermutation. Notably, the BCR idiotype can also give rise to 'immunoglobulin neoantigens'. Here, we provide an overview of current strategies to identify and validate immunoglobulin and non-immunoglobulin neoantigens as well as summarizing studies investigating neoantigens within B-cell LPDs.
Topics: Humans; Antigens, Neoplasm; Immune Checkpoint Inhibitors; Immunotherapy; Neoplasms; Peptides; Immunologic Factors; HLA Antigens; Lymphoproliferative Disorders; Receptors, Antigen, B-Cell
PubMed: 35570070
DOI: 10.1016/j.blre.2022.100969