Journal article
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
Vaccine, Vol.30(9), pp.1624-1635
02/21/2012
Handle:
https://hdl.handle.net/2376/115404
PMID: 22240344
Abstract
► We tested immunogenicity of a CD205-targeted antigen fused to CD40L. ► We tested effectiveness of a single low dose. ► Immunization of MHC class II-matched calves induced significant immune responses. ► Primed immune responses were significantly expanded three weeks post-immunization. ► Mean immune responses tripled within one week post-boost.
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.
Metrics
14 Record Views
Details
- 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
- Creators
- Leo M Njongmeta - Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, 77843, USAJocelyn Bray - Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, 77843, USAChristopher J Davies - Department of Animal, Dairy and Veterinary Sciences, Center for Integrated BioSystems, Utah State University, Logan, UT 84322-4700, USAWilliam C Davis - Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USAChris J Howard - Compton Laboratory, Institute of Animal Health, Compton, Newbury, United KingdomJayne C Hope - Compton Laboratory, Institute of Animal Health, Compton, Newbury, United KingdomGuy H Palmer - Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USAWendy C Brown - Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USAWaithaka Mwangi - Department of Veterinary Pathobiology, Texas A&M University, College Station, TX, 77843, USA
- Publication Details
- Vaccine, Vol.30(9), pp.1624-1635
- Academic Unit
- Veterinary Microbiology and Pathology, Department of; Paul G. Allen School for Global Animal Health
- Publisher
- Elsevier Ltd
- Grant note
- CSREES 2005-01693 / Agriculture and Food Research Initiative Competitive
- Identifiers
- 99900547313201842
- Language
- English
- Resource Type
- Journal article