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CD205 antigen targeting combined with dendritic cell recruitment factors and antigen-linked CD40L activation primes and expands significant antigen-specific antibody and CD4(+) T cell responses following DNA vaccination of outbred animals.
Title | CD205 antigen targeting combined with dendritic cell recruitment factors and antigen-linked CD40L activation primes and expands significant antigen-specific antibody and CD4(+) T cell responses following DNA vaccination of outbred animals. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Njongmeta, LM, Bray, J, Davies, CJ, Davis, WC, Howard, CJ, Hope, JC, Palmer, GH, Brown, WC, Mwangi, W |
Journal | Vaccine |
Volume | 30 |
Issue | 9 |
Pagination | 1624-35 |
Date Published | 2012 Feb 21 |
ISSN | 1873-2518 |
Keywords | Anaplasma marginale, Animals, Antibody Formation, Antigens, CD, B-Lymphocytes, Bacterial Outer Membrane Proteins, Cattle, CD4-Positive T-Lymphocytes, CD40 Ligand, Cell Proliferation, Dendritic Cells, Dose-Response Relationship, Immunologic, Granulocyte-Macrophage Colony-Stimulating Factor, HEK293 Cells, Humans, Immunoglobulin G, Interferon-gamma, Lectins, C-Type, Lymphocyte Activation, Male, Membrane Proteins, Receptors, Cell Surface, Vaccines, DNA |
Abstract | Dendritic cell antigen targeting primes robust immune responses in mouse models. Optimizing this immunization strategy in the actual hosts that require protection will advance development of efficacious contemporary vaccines. In a proof-of-concept study, we tested the immunogenicity of a single, low dose of a novel multi-component DNA construct expressing a CD205-targeted antigen fused to a CD40L minimal functional domain for linked DC activation. The DNA construct was formulated with DNA-encoded Flt3L and GM-CSF for DC recruitment and the formulation was evaluated in MHC class II-matched calves. Immunization of the calves with the CD205 antigen-targeting construct mixed with the cytokine constructs induced significant IFN-γ-secreting CD4(+) T-cells, CD4(+) T-cell proliferation, and antibody responses detectable within one week post-immunization. CD205 antigen-targeting significantly expanded IFN-γ-secreting CD4(+) T-cells, CD4(+) T-cell proliferation, and IgG antibody responses three weeks post-immunization. Nineteen weeks post-priming, the IFN-γ-secreting CD4(+) T-cells, CD4(+) T-cell proliferation, and the IgG titers were waning, but they remained significant. Following boosting at nineteen weeks post-immunization, the immune responses primed by the CD205-targeted antigen underwent rapid recall and the mean response tripled within one week post-boost. Comparative analysis of the immune responses observed one week post-priming versus the responses detected one week post-boost revealed that the average number of the IFN-γ-secreting CD4(+) T-cells observed in the calves immunized with the CD205 antigen targeting construct increased five-fold, the mean CD4(+) T-cell proliferation increased three-fold, whereas the mean IgG antibody titer increased two hundred-fold. These promising outcomes support testing the protective efficacy of CD205-targeted antigens in the calf model. |
DOI | 10.1016/j.vaccine.2011.12.110 |
Alternate Journal | Vaccine |
PubMed ID | 22240344 |