Influence of polypeptide size and intracellular sorting on the induction of epitope-specific CTL responses by DNA vaccines in a mouse model
| Autor: | Alexandra Bojak, Ralf Wagner, Jens Wild, Ludwig Deml |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Signal peptide
Cellular immunity viruses Gene Products gag Genes MHC Class I Biology Epitope DNA vaccination Epitopes Mice Immune system Vaccines DNA Animals Cytotoxic T cell Codon DNA Primers AIDS Vaccines Immunity Cellular Mice Inbred BALB C General Veterinary General Immunology and Microbiology Reverse Transcriptase Polymerase Chain Reaction Public Health Environmental and Occupational Health Gene Products env Molecular biology CTL Infectious Diseases Capsid Antibody Formation HIV-1 Cytokines RNA Molecular Medicine Female Peptides Plasmids T-Lymphocytes Cytotoxic |
| Zdroj: | Vaccine. 22:1732-1743 |
| ISSN: | 0264-410X |
| DOI: | 10.1016/j.vaccine.2004.01.035 |
| Popis: | We have analysed the influence of size, intracellular localisation, and sorting of various human immunodeficiency virus type 1 (HIV-1)-derived Gag and Env polypeptides containing well defined H2 d -restricted cytotoxic T lymphocyte (CTL) epitopes on the induction of a humoral and cellular immune response after DNA vaccination. Thus, expression vectors were generated based on RNA- and codon-optimised genes encoding (i) budding competent full-length Gag, (ii) a myristylation defect mutant GagMyr − , (iii) the isolated p24 capsid moiety of Gag as well as variants of these proteins, which were C-terminally fused HIV gp120-derived V3 epitope (R10I), respectively. These constructs were compared to different minitopes each encoding one of the H2 d -restricted Gag epitopes A9I and E10F or the V3 epitope R10I that were directly linked to the C-terminus of an Ad2-E3 protein-derived ER signal peptide. Immunological evaluation of these constructs in BALB/c mice revealed that both, the budding competent as well as the intracellular Gag proteins were—irrespective of their molecular weights—equally efficient in the priming of Gag-specific humoral and cellular immune responses. In addition, the capacity of these constructs to stimulate Gag-specific humoral as well as H2-K d and H2-L d restricted cellular immune responses was not influenced by C-terminal fusion of the immunodominant H2-D d restricted V3 epitope. Chimeric GagV3 polyproteins encoding all three major CTL epitopes within a continuous polyprotein were more efficient to stimulate epitope-specific cellular immune responses than the selected minitopes. In addition, the minitopes failed to induce epitope-specific antibody responses. These results clearly show the advantages of complex polypeptides over minitopes regarding the induction of strong humoral and cellular immune responses. |
| Databáze: | OpenAIRE |
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