Why Don't We Have a Vaccine Against Autoimmune Diseases? - A Review
Creator
Rosenthal Ken S; Carambula Roy; Zimmerman Daniel H
Publisher
Journal of Clinical & Cellular Immunology
Date
2019
2019
Description
This review examines some of the reasons why we don't have a vaccine against autoimmune diseases and highlights the progress that has been made. Many autoimmune diseases, such as rheumatoid arthritis (RA), multiple sclerosis (MS) and type 1 diabetes (T1D), are driven by autoimmune T cell responses. Unlike vaccines for most infectious diseases, which elicit antibody responses, are intended for immuno-naive individuals and considered preventative, a vaccine for an autoimmune disease must be therapeutic and resolve or control the on-going autoimmune response and condition in the diseased host. Despite these differences, many of the same considerations for infectious disease vaccines must also be addressed to develop a therapeutic vaccine for autoimmune diseases. The disease initiator/triggers, antigens and autoantigens, nature of the immunopathogenic and protective/therapeutic immune response will be compared for infectious and autoimmune diseases as will approaches for developing vaccines including formulations, animal models and indicators of success. The rationale for a therapeutic vaccine for RA will be discussed in greater detail with a relatively limited discussion of T1D, MS and other autoimmune diseases.
Subject
Autoimmune; Immunotherapy; Multiple sclerosis; Rheumatoid arthritis; Type 1 diabetes; Vaccine
Concurrent treatment of chronic psoriasis and asthma with ustekinumab.
Creator
Amarnani Ajay; Rosenthal Ken S; Mercado Jorge M; Brodell Robert T
Publisher
The Journal of dermatological treatment
Date
2014
2014-02
Description
A 56-year-old woman with a 40-year history of guttate flares of psoriasis associated with stress and infection as well as chronic asthma was treated with subcutaneous injections of ustekinumab, repeated after 1 month and then every 3 months. Her psoriasis completely resolved, and her capacity for exercise was markedly increased and asthma maintenance medications were no longer needed. Ustekinumab is a human monoclonal antibody that binds the p40 subunit of IL-12 and IL-23 to limit the progression of the Th1 and Th17 inflammatory immune responses that maintain many autoimmune and inflammatory diseases. Th17-related responses drive inflammation during late stages of chronic asthma and can also be blocked by ustekinumab. Blocking the underlying cytokine-mediated inflammatory responses for psoriasis with ustekinumab can also treat other chronic inflammatory diseases.
Immune peptide enhancement of peptide based vaccines.
Creator
Rosenthal Ken S
Publisher
Frontiers in bioscience : a journal and virtual library
Date
2005
2005-01
Description
Vaccines optimize the presentation of an immunogen to the immune system, oftentimes enhancing or replacing the natural activators of antigen presenting cells in order to promote the delivery and the response of T and B lymphocytes to the immunogen. The purpose of this series is to describe new technologies which allow vaccine design, based on our understanding of the immune response, using different approaches to immune peptide enhancement of peptide based vaccines. In this introduction to the series entitled, "Immune Peptide Enhancement of Peptide Based Vaccines", some of the immunological concepts relevant to vaccine design are presented.
Subject
Humans; Animals; Drug Design; B-Lymphocytes/immunology; T-Lymphocytes/immunology; Cancer Vaccines/chemistry; Epitopes/chemistry; Immune System/pathology; Peptides/*chemistry; Vaccines; Subunit/*chemistry
LEAPS Vaccine Incorporating HER-2/neu Epitope Elicits Protection That Prevents and Limits Tumor Growth and Spread of Breast Cancer in a Mouse Model.
Creator
Rosenthal Ken S; Stone Sarah; Koski Gary; Zimmerman Daniel H
Publisher
Journal of immunology research
Date
2017
1905-07
Description
The prototype J-LEAPS T cell vaccine for HER-2/neu breast cancer (J-HER) consists of the murine HER-2/neu66-74 H-2(d) CD8 T cell epitope covalently attached through a triglycine linker to the J-immune cell binding ligand (ICBL) (human beta2 microglobulin38-50 peptide). The J-ICBL was chosen for its potential to promote Th1/Tc1 responses. In this proof-of-concept study, the ability of J-HER to prevent or treat cancer was tested in the TUBO cell-challenged BALB/c mouse model for HER-2/neu-expressing tumors. The J-HER vaccine was administered as an emulsion in Montanide ISA-51 without the need for a more potent adjuvant. When administered as a prophylactic vaccination before tumor challenge, J-HER protected against tumor development for at least 48 days. Despite eliciting protection, antibody production in J-HER-immunized, TUBO-challenged mice was less than that in unimmunized mice. More importantly, therapeutic administration of
Strain-dependent structural variants of herpes simplex virus type 1 ICP34.5 determine viral plaque size, efficiency of glycoprotein processing, and viral release and neuroinvasive disease potential.
Creator
Mao Hanwen; Rosenthal Ken S
Publisher
Journal of virology
Date
2003
2003-03
Description
The ability of certain strains of herpes simplex virus type 1 (HSV-1) to cause encephalitis or neuroinvasive disease in the mouse upon peripheral infection is dependent on a combination of activities of specific forms of viral proteins. The importance of specific variants of ICP34.5 to neuroinvasive disease potential and its correlation with small-plaque production, inefficient glycoprotein processing, and virus release were suggested by comparison of ICP34.5 from the SP7 virus, originally obtained from the brain of a neonate with disseminated disease, and the tissue culture-passaged progeny of SP7 (SLP5 and SLP10) and the KOS321 virus. SLP5, SLP10, and KOS321 are attenuated and exhibit a large-plaque phenotype, including efficient glycoprotein processing and viral release. We show that expression of the KOS321 ICP34.5 protein in cells infected with SP7 or ICP34.5 deletion mutants promotes large plaque formation and efficient viral glycoprotein processing, while expression of the SP7 ICP34.5 protein decreases efficiency of viral glycoprotein processing. In addition, a recombinant virus, 4hS1, with the SP7 ICP34.5 gene replacing the KOS321-like ICP34.5 gene in the SLP10a background, rescues the small-plaque phenotype and neuroinvasive disease. The major difference in the ICP34.5 gene product is the number of Pro-Ala-Thr repeats in the middle region of the protein, with 18 for SP7 and 3 for KOS321. Strain-dependent differences in the ICP34.5 protein can therefore alter the tissue culture behavior and the virulence of HSV-1.
J-LEAPS peptide and LEAPS dendritic cell vaccines.
Creator
Rosenthal Ken S; Taylor Patricia; Zimmerman Daniel H
Publisher
Microbial biotechnology
Date
2012
2012-03
Description
The J-LEAPS vaccines contain a peptide from beta-2-microglobulin covalently attached to disease-related peptides of 8-30 amino acids which contain a T cell epitope. The J-LEAPS vaccines can initiate a protective Th1 immune response or modulate an ongoing Th17 autoimmune response to the peptide. J-LEAPS vaccines activate and direct the nature of the subsequent immune response by promoting the maturation of precursor cells into a unique type of dendritic cell that produces interleukin 12, but not IL-1 or tumour necrosis factor, and presents the antigenic peptide to T cells. Adoptive transfer of JgD-LEAPS dendritic cells, matured with an anti-HSV-1 vaccine, promoted antigen-specific Th1 protection against lethal challenge with the virus. J-LEAPS peptide immunogens and J-LEAPS dendritic cell vaccines have potential applications for antimicrobial prevention and therapy, treatment of autoimmune diseases, and for cancer immunotherapy.
Maturation of dendritic cell precursors into IL12-producing DCs by J-LEAPS immunogens.
Creator
Taylor Patricia R; Paustian Christopher C; Koski Gary K; Zimmerman Daniel H; Rosenthal Ken S
Publisher
Cellular immunology
Date
2010
1905-07
Description
LEAPS (ligand epitope antigen presentation system) vaccines consist of a peptide containing a major histocompatibility antigen binding peptide conjugated to an immune cell binding ligand (ICBL) such as the 'J' peptide from beta-2-microglobulin. Treatment of monocytes, monocytes plus GMCSF, or monocytes plus GMCSF and IL4 with JgD (containing a peptide from gD of herpes simplex virus type 1) or JH (with a peptide from HIV p17 gag protein) was sufficient to promote their maturation into Interleukin 12 producing dendritic cells. JgD-dendritic cells supported allotypic activation of T cells to produce Th1-related cytokines.