Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Adjuvanted multi-epitope vaccines protect HLA-A*11:01 transgenic mice against Toxoplasma gondii
Kamal El Bissati, … , Craig W. Roberts, Rima McLeod
Kamal El Bissati, … , Craig W. Roberts, Rima McLeod
Published September 22, 2016
Citation Information: JCI Insight. 2016;1(15):e85955. https://doi.org/10.1172/jci.insight.85955.
View: Text | PDF
Research Article Vaccines

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

  • Text
  • PDF
Abstract

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.

Authors

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 Fraczek, Catherine A. Reardon, John Sidney, Jeff Alexander, Alessandro Sette, Tom Vedvick, Chris Fox, Jeffrey A. Guderian, Steven Reed, Craig W. Roberts, Rima McLeod

×

Figure 6

DNA prime-protein boost regimen.

Options: View larger image (or click on image) Download as PowerPoint
DNA prime-protein boost regimen.
(A) pMB75.6 vector used as a DNA vaccin...
(A) pMB75.6 vector used as a DNA vaccine vector for this study. Lane P: pMB75.6 plasmid; lane 2: pMB75.6 plasmid digested with EcoRI and BglII; lane M: KB ladder. (B) T. gondii brain cysts luciferase expression was reduced in HLA-A*11:01 mice immunized with DNA/ protein boost at 21 days after challenge with 2,000 T. gondii ME49-Fluc (Type II) expressing luciferase. (C) Xenogen imaging of brain ex vivo following the injection of luciferin into the retro-orbital plexus and then exposure of the brain to luciferin solution. n = 5 per group, *P = 0.0008, **P = 0.004, ***P = 0.004 (Student’s t test after one-way ANOVA). (D) Enumeration of cysts was performed with brains of mice challenged 21 days after final immunization. These experiments were performed at least 2 times, and one representative experiment of 2 is shown:.n = 5 control and 5 immunized mice. *P = 0.002, **P = 0.003, ***P = 0.004; Student’s t test was used to compere the groups. For C and D, the plots show median, with box extending from the 25th to 75th percentile and the whiskers extending from minimum and maximum values of the data set. One-way ANOVA was performed before the Student’s t test to determine whether there was an overall difference between the groups.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts