CEL-1000 - a peptide with adjuvant activity or Th1 immune responses
Research & Experimental Medicine; Immunology; cytokines; antibodies; beta-2-microglobulin; vaccines; dna; antigens; CEL-1000; epitope; gamma interferon; IgG2a antibodies; liposomes
CEL-1000 (derG, DGQEEKAGVVSTGLIGGG) is a small immunomodulatory peptide which delivers demonstrated protective activity in two infectious disease challenge models (HSV and malaria) and an allogenic tumor vaccine model. CEL-1000 and other activators (defensin-beta, CpG ODN, and imiquimod) of the innate immune system promote IFN-gamma-associated protective responses. CEL-1000 is an improved form of peptide G (a peptide from human MHC II beta chain second domain, aa 135-149) known to enhance immune responses of other immunogenic peptides. Since defensin-P, CpG ODN, and imiquimod have been shown to possess adjuvant activity, we investigated the adjuvant effect of peptide G and CEL-1000 as conjugates with HIV and malaria peptides. Antibody titers and isotypes were evaluated on serum taken from select days following immunization. Results for CEL-1000 and G peptide conjugates were compared with results for KLH conjugates of the same HIV peptide from the p 17 molecule (87-116) referred to as HGP-30. Studies demonstrated that comparable titers were seen on day 28, 42, 63, and 77 with either G or KLH-HGP-30 peptide conjugates. In another study, CEL-1000 conjugates (CEL-1000-HGP-30) demonstrated a 4-10-fold higher titer antibody response than seen with several other peptide conjugates of the same HGP-30 peptide. Improved adjuvant activity of CEL-1000 in peptide conjugates was also demonstrated by a shift in the antibody isotypes toward a Th1 response (IgG2a). The IgG2a/IgG1, ratio for G-HGP-30 HIV or KLH-HGP-30 HIV conjugates were lower than for the CEL-1000-HGP-30 HIV conjugate. A similar favoring of the IgG2a/IgG1 ratio was seen for a malaria peptide conjugate (CEL-1000-SF/GF) compared to the un-conjugated peptide (SF-GF). CEL-1000 also showed adjuvant activity in an allogenic tumor vaccine model. As expected for an adjuvant, CEL-1000 or G does not induce detectable self-directed or cross reactive antibodies. CEL-1000 is currently being investigated for use as an adjuvant with conventional vaccines. It is expected that IgG2a antibodies would be preferably generated by CEL-1000 adjuvancy and could enhance in vivo clearance of antigens or pathogens. (C) 2004 Elsevier Ltd. All rights reserved.
Charoenvit Y; Goel N; Whelan M; Rosenthal K S; Zimmerman D H
Vaccine
2004
2004-06
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.vaccine.2003.11.062" target="_blank" rel="noreferrer noopener">10.1016/j.vaccine.2003.11.062</a>
A L.E.A.P.S. heteroconjugate vaccine containing a T cell epitope from HSV-1 glycoprotein D elicits Th1 responses and protection.
Amino Acid Sequence; Animals; CD4-Positive T-Lymphocytes/immunology; CD8-Positive T-Lymphocytes/immunology; Conjugate/immunology; Delayed/immunology; Enzyme-Linked Immunosorbent Assay; Epitopes/*immunology; Female; Herpes Simplex Virus Vaccines/*immunology; Herpes Simplex/pathology/prevention & control; Herpesvirus 1; Human/*immunology; Hypersensitivity; Inbred BALB C; Interferon-gamma/biosynthesis; Lymphocyte Count; Mice; Molecular Sequence Data; Peptides/immunology; Th1 Cells/*immunology; Vaccines; Viral Envelope Proteins/*immunology
The L.E.A.P.S. heteroconjugate vaccine antigen (JgD), composed of a T cell epitope from glycoprotein D (gD(8-23)) of herpes simplex virus (HSV) linked with a peptide sequence from beta-2-microglobulin (aa38-50), elicited protection against lethal intraperitoneal (IP) challenge and prevented disease signs in most, and limited disease progression, for the rest of BALB/c mice challenged in the epidermal abrasion-zosteriform spread mouse infection model. JgD elicited a Th1 response in vaccinated mice as indicated by delayed type hypersensitivity (DTH) responses to HSV antigen, and gD and virion specific antibodies with an IgG2a/IgG1 \textgreater1. Vaccination with the JgD peptide delayed the onset of disease signs, reduced severity of the disease and reduced mortality rates in mice with different MHC backgrounds as compared to their respective control mice. CD8 cells were demonstrated as important for initiation of the immune response to JgD and CD4 cells and interferon gamma (IFN-gamma) for delivering immune protection in BALB/c mice, as indicated in monoclonal antibody ablation studies. JgD, and other
Goel N; Rong Q; Zimmerman D; Rosenthal K S
Vaccine
2003
2003-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0264-410x(03)00429-8" target="_blank" rel="noreferrer noopener">10.1016/s0264-410x(03)00429-8</a>
Why Don't We Have a Vaccine Against....? Part 2. Bacteria
antibacterial vaccines; attenuated; conjugate vaccines; disease; Immunology; Infectious Diseases; model; oral vaccines; pertussis; toxoid; vaccine; vaccines
Despite the large number of vaccines, this review asks the question: why do we not have vaccines for all infectious diseases? The first of this series discussed basics of vaccine immunology, new approaches, and outlined some of the difficulties and approaches that are being taken for antiviral vaccines. The second part of the series focuses on antibacterial vaccines and the approaches that are being taken to develop vaccines for some of the most important bacteria.
Rosenthal K S; Kuntz A; Sikon J
Infectious Diseases in Clinical Practice
2016
2016-03
Journal Article
<a href="http://doi.org/10.1097/ipc.0000000000000352" target="_blank" rel="noreferrer noopener">10.1097/ipc.0000000000000352</a>
Immunization with a LEAPS heteroconjugate containing a CTL epitope and a peptide from beta-2-microglobulin elicits a protective and DTH response to herpes simplex virus type 1.
*Epitopes; Amino Acid Sequence; Animals; beta 2-Microglobulin/immunology; Conjugate/immunology; Cytotoxic/*immunology; Delayed/*etiology; Female; Herpesvirus 1; Human/*immunology; Hypersensitivity; Immediate-Early Proteins/*immunology; Immunization; Inbred BALB C; Mice; Molecular Sequence Data; Peptide Fragments/*immunology; T-Lymphocyte; T-Lymphocytes; Vaccines; Viral Vaccines/*immunology
A ligand epitope antigen presentation system (LEAPS) heteroconjugate vaccine containing a CTL epitope (H1) from the HSV-1 immediate early protein ICP27 (322-332) and a peptide sequence (J) from beta-2-microglobulin (35-50) elicited protection from intraperitoneal viral challenge and promoted DTH responses. The H1 peptide and other H1 containing heteroconjugates did not elicit protection or DTH responses. Antibody to the H1 peptide could not be detected by ELISA following vaccination with peptide, heteroconjugate or natural infection. The LEAPS heteroconjugate appears to prime a Thl-like response which is subsequently boosted by infection. These studies show that attachment of the J peptide can make a CTL epitope into a vaccine which is immunogenic and promotes a protective Th1 type of response.
Rosenthal K S; Mao H; Horne W I; Wright C; Zimmerman D
Vaccine
1999
1999-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0264-410x(98)00231-x" target="_blank" rel="noreferrer noopener">10.1016/s0264-410x(98)00231-x</a>
Immune peptide enhancement of peptide based vaccines.
Humans; Animals; Drug Design; B-Lymphocytes/immunology; T-Lymphocytes/immunology; Cancer Vaccines/chemistry; Epitopes/chemistry; Immune System/pathology; Peptides/*chemistry; Vaccines; Subunit/*chemistry
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.
Rosenthal Ken S
Frontiers in bioscience : a journal and virtual library
2005
2005-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.2741/1543" target="_blank" rel="noreferrer noopener">10.2741/1543</a>
Gastrointestinal Infections in the Setting of Natural Disasters
Cholera; Earthquakes; Floods; Gastrointestinal illness; Hepatitis A; Hepatitis E; Hurricanes; Infectious Diseases; Norovirus; Tsunamis; Typhoid fever; vaccines
Gastrointestinal illness following natural disasters is a common occurrence and often results from the disruption of potable water supplies. The risk for outbreaks of gastrointestinal illness is higher in developing countries because of fewer available resources and poorer infrastructure. But industrialized countries are not immune from this problem, as demonstrated by an outbreak of gastroenteritis from norovirus that followed in the wake of Hurricane Katrina in 2005. Rates of gastrointestinal illness following natural disasters are influenced by the endemicity of specific pathogens in the affected region before the disaster, the type of disaster itself, the availability of health care resources, and the response by public health personnel after the disaster. Ensuring the uninterrupted supply of safe drinking water following a natural disaster, like adding chlorine, is the most important strategy to prevent outbreaks of gastrointestinal illness.
Watkins R R
Current Infectious Disease Reports
2012
2012-02
Journal Article
<a href="http://doi.org/10.1007/s11908-011-0225-5" target="_blank" rel="noreferrer noopener">10.1007/s11908-011-0225-5</a>
The LEAPS approach to vaccine development
beta-2-microglobulin; binding-site; Biochemistry & Molecular Biology; Cell Biology; class-ii molecules; dc; dendritic cells; flt3 ligand fl; herpes simplex virus; HIV; human; immune responses; in-vivo; LEAPS constructs; major histocompatibility complex; peptide; protection; review; t-lymphocytes; th1 immune-responses; vaccines
The Ligand Epitope Antigen Presentation System ( L. E. A. P. S. TM) approach to vaccine development utilizes immune peptides to promote the immunogenicity and influence the type of immune response generated towards epitopes in peptides which may be too small to elicit an immune response. The covalent attachment of these immune peptides to the antigenic peptide promotes the interaction of the epitope with T cells ( T cell binding ligand (TCBL)) or antigen presenting cells ( immune cell binding ligand (ICBL)) and ultimately promotes binding with the T cell receptor on CD4 or CD8 T cells. The "J" ICBL/TCBL peptide derived from the beta-2-microglobulin chain of MHC I molecules promotes Th1 type responses to the antigenic peptide while the "G" ICBL/TCBL peptide derived from the beta chain of MHC II molecules promotes Th2 types of responses. The efficacy of this approach has been demonstrated by characterization of the immune responses to L. E. A. P. S. vaccines and by elicitation of protection from infectious challenge with herpes simplex virus and other pathogens. The protection studies show that the L. E. A. P. S. approach allows customization of the immune response appropriate for inducing protection from disease. The theory, background, examples and studies of the mechanism of action of the L. E. A. P. S. vaccines will be discussed.
Zimmerman D H; Rosenthal K S
Frontiers in Bioscience
2005
2005-01
Journal Article
<a href="http://doi.org/10.2741/1572" target="_blank" rel="noreferrer noopener">10.2741/1572</a>