Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii.

نویسندگان

  • Kamal El Bissati
  • Aziz A Chentoufi
  • Paulette A Krishack
  • Ying Zhou
  • Stuart Woods
  • Jitender P Dubey
  • Lo Vang
  • Joseph Lykins
  • Kate E Broderick
  • Ernest Mui
  • Yasuhiro Suzuki
  • Qila Sa
  • Stephanie Bi
  • Nestor Cardona
  • Shiv K Verma
  • Laura Frazeck
  • Catherine A Reardon
  • John Sidney
  • Jeff Alexander
  • Alessandro Sette
  • Tom Vedvick
  • Chris Fox
  • Jeffrey A Guderian
  • Steven Reed
  • Craig W Roberts
  • Rima McLeod
چکیده

We created and tested multi-epitope DNA or protein vaccines with TLR4 ligand emulsion adjuvant (gluco glucopyranosyl lipid adjuvant in a stable emulsion [GLA-SE]) for their ability to protect against Toxoplasma gondii in HLA transgenic mice. Our constructs each included 5 of our best down-selected CD8+ T cell-eliciting epitopes, a universal CD4+ helper T lymphocyte epitope (PADRE), and a secretory signal, all arranged for optimal MHC-I presentation. Their capacity to elicit immune and protective responses was studied using immunization of HLA-A*11:01 transgenic mice. These multi-epitope vaccines increased memory CD8+ T cells that produced IFN-γ and protected mice against parasite burden when challenged with T. gondii. Endocytosis of emulsion-trapped protein and cross presentation of the antigens must account for the immunogenicity of our adjuvanted protein. Thus, our work creates an adjuvanted platform assembly of peptides resulting in cross presentation of CD8+ T cell-eliciting epitopes in a vaccine that prevents toxoplasmosis.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Human immunome, bioinformatic analyses using HLA supermotifs and the parasite genome, binding assays, studies of human T cell responses, and immunization of HLA-A*1101 transgenic mice including novel adjuvants provide a foundation for HLA-A03 restricted CD8+T cell epitope based, adjuvanted vaccine protective against Toxoplasma gondii

BACKGROUND Toxoplasmosis causes loss of life, cognitive and motor function, and sight. A vaccine is greatly needed to prevent this disease. The purpose of this study was to use an immmunosense approach to develop a foundation for development of vaccines to protect humans with the HLA-A03 supertype. Three peptides had been identified with high binding scores for HLA-A03 supertypes using bioinfor...

متن کامل

Identification of Mycobacterium tuberculosis CTL Epitopes Restricted by HLA-A*0201 in HHD Mice

CD8+ T cells are thought to play an important role in protective immunity to tuberculosis. The major histocompatibility complex class I subtype HLA-A*0201 is one of the most prevalent class I alleles, with a frequency of over 30% in most populations. HLA-A*0201 transgenic, H-2Db/mouse beta2-microglobulin double-knockout mice (HHD) which express human HLA-A*0201 but no mouse class I, was shown t...

متن کامل

Establishment of an HLA-A*0201 human papillomavirus type 16 tumor model to determine the efficacy of vaccination strategies in HLA-A*0201 transgenic mice.

With the increasing generation of new cancer vaccine strategies, there is also an increasing demand for preclinical models that can carefully predict the efficacy of these vaccines in humans. However, the only tumor models available to study vaccines against human papillomavirus (HPV) 16 have been developed in C57BL/6 mice. To test the HLA-restricted capabilities of vaccination strategies, it i...

متن کامل

DNA Vaccines Encoding Toxoplasma gondii Cathepsin C 1 Induce Protection against Toxoplasmosis in Mice

Toxoplasma gondii cathepsin C proteases (TgCPC1, 2, and 3) are important for the growth and survival of T. gondii. In the present study, B-cell and T-cell epitopes of TgCPC1 were predicted using DNAstar and the Immune Epitope Database. A TgCPC1 DNA vaccine was constructed, and its ability to induce protective immune responses against toxoplasmosis in BALB/c mice was evaluated in the presence or...

متن کامل

Immunization of C57BL/6 Mice with GRA2 Combined with MPL Conferred Partial Immune Protection against Toxoplasma gondii

BBackground: We have previously reported that immunization with GRA 2 antigen of Toxoplasma gondii induces protective immunity in CBA /J (H2k) and BALB/c mice (H2d). We aimed to examine whether immunization of a distinct strain of rodent with recombinant dense granule antigens (GRA2) combined with monophosphorryl lipid A (MPL) adjuvant elicits protective immune response against T. gondii. Metho...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • JCI insight

دوره 1 15  شماره 

صفحات  -

تاریخ انتشار 2016