Immunotherapy with CpG DNA conjugated with T-cell epitope peptide of an allergenic Cry j 2 protein is useful for control of allergic conditions in mice.
Immunotherapy using T-cell epitope peptides or CpG DNA conjugated with allergenic protein is useful, although the mechanisms of these therapies differ. However, the combination of CpG DNA and peptide, but not protein, had not been documented. Therefore, we investigated CpG DNA conjugated with peptide to obtain positive synergistic effects. In the first experiment, mice were vaccinated with a conjugate of CpG DNA and Cry j 2 T-cell epitope peptide p246-259 (CpG-peptide); a mixture of CpG DNA and peptide (CpG+peptide); peptide alone, or PBS alone, and immunized with Cry j 2. In the second experiment, mice were immunized with Cry j 2 and injected with CpG-peptide, CpG+peptide, peptide only, or PBS only. In both experiments, Cry j 2-specific IgE, IL-4, and IL-5 were significantly lower in mice given CpG-peptide, versus those given CpG+peptide, peptide alone, or PBS alone. However, IgG2a, IgG2b and IFN-gamma did not increase in mice injected with CpG-peptide. In the third experiment, CpG-peptide significantly attenuated nasal symptoms (sneezing and nasal rubbing) compared to CpG+peptide, peptide alone, or PBS alone. Mice were also injected with a conjugate of CpG DNA and Cry j 2 protein (CpG-Cry j 2) or CpG-peptide to compare prime responses. Mice vaccinated with CpG-Cry j 2 generated Cry j 2-specific IgG1, whereas those vaccinated with CpG-peptide did not produce IgG1. This study demonstrated, for the first time, that immunotherapy with CpG DNA conjugated with a T-cell peptide is useful in preventing and treating allergic conditions.
Suzuki
Motohiko
M
Department of Surgery and Microbiology and Immunology, University of Western Ontario 339 Windermere Road, London, Canada N6A5A5. msuzuki5@uwo.ca
Ohta
Nobuo
N
Min
Wei-Ping
WP
Matsumoto
Tamami
T
Min
Rui
R
Zhang
Xusheng
X
Toida
Kazunori
K
Murakami
Shingo
S
D000818:Animals; D018899:CpG Islands; D004247:DNA / Q000737:chemistry / Q000627:therapeutic use*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000627:therapeutic use*; D007073:Immunoglobulin E / Q000097:blood; D007167:Immunotherapy; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use*; D010940:Plant Proteins / Q000737:chemistry / Q000627:therapeutic use*; D006255:Rhinitis, Allergic, Seasonal / Q000628:therapy*; D012912:Sneezing; D013154:Spleen / Q000166:cytology / Q000276:immunology
C065291:Cry j II protein, Cryptomeria japonica; D018984:Epitopes, T-Lymphocyte; D015848:Interleukin-5; D010455:Peptides; D010940:Plant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E; D004247:DNA