Single chain MHC I trimer-based DNA vaccines for protection against Listeria monocytogenes infection.

Abstract

To circumvent limitations of poor antigen presentation and immunogenicity of DNA vaccines that target induction of CD8(+) T cell immunity, we have generated single chain MHC I trimers (MHC I SCTs) composed of a single polypeptide chain with a linear composition of antigenic peptide, β2-microglobulin, and heavy chain of a MHC class I molecule connected by flexible linkers. Because of its pre-assembled nature, the SCT presents enhanced expression and presentation of the antigenic peptide/MHC complexes at the cell surface. Furthermore, DNA vaccination with a plasmid DNA encoding an SCT incorporating an immunodominant viral epitope elicited protective CD8(+) T cell responses against lethal virus infection. To extend these findings, here we tested the efficacy of SCT DNA vaccines against bacterial infections. In a mouse infection model of Listeria monocytogenes, the SCT DNA vaccine encoding H-2K(d) and the immunodominant peptide LLO 91-99 generated functional primary and memory peptide-specific CD8(+) T cells that confer partial protection against L. monocytogenes infection. DNA immunization of K(d)/LLO(91-99) SCTs generated functional memory CD8(+) T cells independently of CD4(+) T cells, although the expression of cognate or non-cognate CD4(+) helper T cell epitopes further enhanced the protective efficacy of SCTs. Our study further demonstrates that the SCT serves as a potent platform for DNA vaccines against various infectious diseases.

• Authors: Sojung Kim, Adam Zuiani, Javier A Carrero, Ted H Hansen
• Journal: Vaccine (Vaccine) Vol. 30 Issue 12 Pg. 2178-86 (Mar 09 2012) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 22285270 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Antigens, Bacterial
• Antigens, CD
• Epitopes, T-Lymphocyte
• Histocompatibility Antigens Class I
• Immunodominant Epitopes
• Recombinant Fusion Proteins
• Vaccines, DNA
• beta 2-Microglobulin
• Interferon-gamma

Topics

• Animals
• Antigens, Bacterial (genetics, immunology)
• Antigens, CD (analysis)
• Bacterial Load
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Enzyme-Linked Immunospot Assay
• Epitopes, T-Lymphocyte (genetics, immunology)
• Flow Cytometry
• Histocompatibility Antigens Class I (genetics, immunology)
• Humans
• Immunodominant Epitopes (genetics, immunology)
• Interferon-gamma (metabolism)
• Leukocytes, Mononuclear (immunology)
• Listeria monocytogenes (immunology)
• Listeriosis (immunology, prevention & control)
• Liver (microbiology)
• Lymphocyte Subsets (chemistry, immunology)
• Mice
• Mice, Inbred BALB C
• Plasmids
• Recombinant Fusion Proteins (genetics, immunology)
• Spleen (immunology, microbiology)
• Vaccines, DNA (administration & dosage, immunology)
• beta 2-Microglobulin (genetics, immunology)