Progress for Autoimmune Disease Vaccine (Part Two)

  • 2.3 Type 1 diabetes

    Type 1 diabetes is a T cell-mediated autoimmune disease against islets (the autoimmune disease characterized by monocyte infiltration in islet cells and production of islets (autoantibodies of cells, activated autoreactive T cells versus islets) (The cell attacks, resulting in the lack of insulin secretion, diabetes). The autoantigens associated with Type 1 diabetes have been found to be insulin, proinsulin, glutamate decarboxylase GAD65, protein phosphatase I-A2 and heat shock protein HSP60. NOD mice (Nonobese diabetic mice) are recognized as Type 1 diabetes animal models.

    In 1981, Ben-nun proposed that inactivated autoreactive T cells as a vaccine (TCV vaccination, TCV) can specifically prevent and treat autoimmune diseases. With the development of modern immunology, it has been found that CD4+CD25+Treg is immunosuppressive and produces specific inhibition after TCR-mediated signal-stimulated activation, thereby eliminating autoreactive T cells. CD4+CD25+Treg can be used to develop a T cell vaccine with therapeutic potential in a reverse rotation model of Type 1 diabetes.

    2.4 Systemic lupus erythematosus (SLE)

    SLE is an immune complex disease caused by type III hypersensitivity reaction. SLE patients form immune complexes by self-IgG antibodies and nuclear antigens produced by immune responses to autologous nuclear antigens, and activate complement to cause extensive inflammatory small blood vessel damage. NZBXNZW F1 mice and their related lines from different sources (NZW2410) are good SLE mouse models.

    Polypeptides based on autoantibody complementarity determining regions have been shown to inhibit SLE-related, T, B cell responses, up-regulation of TGF-β in in vitro assays and in the NZBXNZW F1 mouse model, and are expected to be used as peptide vaccines for SLE for clinical treatment.

    2.5 Rheumatoid arthritis (RA)

    RA is a systemic autoimmune inflammatory disease with unclear etiology. The main clinical manifestations are chronic, progressive, symmetrical and multiple synovial arthritis and extra-articular lesions. The immune response against heat shock protein (HSP) is associated with experimental and clinical RA pathogenesis.

    The bacterial heat shock protein has high homology with human heat shock proteins, and is derived from Escherichia coli and many other bacteria: the consensus sequence QKRAA of the DanJ class HSP as an epitope can specifically induce a strong immune response in RA patients. DanJp1 is an HSP-based peptide that binds to most HLA alleles and inhibits inflammatory responses. Eight months of oral administration of DanJp1 in patients with early RA showed no side effects, and a large number of antigen-specific T cell responses were converted from a Th1 type before the inflammatory response to a regulatory T cell phenotype.

    1. Therapeutic vaccines in novel vaccine researches

    The trend in novel vaccine research is to develop therapeutic vaccines against asymptomatic carriers or diseased patients who have been infected with the causal agent. Therapeutic vaccine research for autoimmune diseases is also rapidly developing and has broad application prospects. The ideal effect of treating autoimmune diseases is to eliminate self-antigen-specific spontaneous immune responses without interfering with immune responses against other antigens. Therapeutic vaccines for autoimmune diseases also comply with this principle.

    A therapeutic vaccine based on autoantigen similarity is used to specifically target autoreactive pathogenicity. Cells are a pathway for inhibition of autoimmune diseases. This approach requires an understanding of the autoantigen that causes the disease, and it is clear that taking this antigen does not induce or restore the pathogenic response. Systemic immunotherapy based on autoantigens has a variety of mechanisms, such as induction, apoptosis, inducting of regulatory T cells, T cell receptor antagonism, and immune migration. However, its clinical applicability has problems: first, the key autoantigens that trigger the autoimmune process are not clear; second, due to the presence of epitope expansion, MHC/peptide ligand complexes derived from different self-proteins will be presented during clinical presentation. Promote the development of autoimmune diseases; third, the diversity of autoreactive T cells in autoimmune diseases may be much higher than previously thought. Therefore, the pathway to target a single TCR may not be sufficient for the treatment of autoimmune diseases. The most effective treatment of pathogenic and protective cells in an immune response may ultimately rely on antigen-based and a combination of cytokines and cell-based therapies, or may rely on other immune-modulators to selectively target Reactive T cells to the self and make the autoreactivity. The cells deviate from their own offensive response.

       Therefore, the development of future therapeutic vaccines should focus on a combination of treatments that target different pathogenic processes, which will help to more fully explore the potential of therapeutic vaccines in the treatment of autoimmune diseases.



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