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Gene gun DNA immunization of cattle induces humoral and CD4 T-cell-mediated immune responses against the Theileria parva polymorphic immunodominant molecule

Theileria parva kills over one million cattle annually in sub-Saharan Africa. Parasite genetic complexity, cellular response immunodominance, and bovine MHC diversity have precluded traditional vaccine development. One potential solution is gene gun (GG) immunization, which enables simultaneous admi...

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Detalles Bibliográficos
Autores principales: Fry, Lindsay M., Bastos, Reginaldo G., Stone, Brad C., Williams, Laura B., Knowles, Donald P., Murphy, Sean C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411927/
https://www.ncbi.nlm.nih.gov/pubmed/30782490
http://dx.doi.org/10.1016/j.vaccine.2019.02.009
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author Fry, Lindsay M.
Bastos, Reginaldo G.
Stone, Brad C.
Williams, Laura B.
Knowles, Donald P.
Murphy, Sean C.
author_facet Fry, Lindsay M.
Bastos, Reginaldo G.
Stone, Brad C.
Williams, Laura B.
Knowles, Donald P.
Murphy, Sean C.
author_sort Fry, Lindsay M.
collection PubMed
description Theileria parva kills over one million cattle annually in sub-Saharan Africa. Parasite genetic complexity, cellular response immunodominance, and bovine MHC diversity have precluded traditional vaccine development. One potential solution is gene gun (GG) immunization, which enables simultaneous administration of one or more DNA-encoded antigens. Although promising in murine, porcine, and human vaccination trials, bovine GG immunization studies are limited. We utilized the model T. parva antigen, polymorphic immunodominant molecule (PIM) to test bovine GG immunization. GG immunization using a mammalian codon optimized PIM sequence elicited significant anti-PIM antibody and cell-mediated responses in 7/8 steers, but there was no difference between immunized and control animals following T. parva challenge. The results suggest immunization with PIM, as delivered here, is insufficient to protect cattle from T. parva. Nonetheless, the robust immune responses elicited against this model antigen suggest GG immunization is a promising vaccine platform for T. parva and other bovine pathogens.
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spelling pubmed-64119272019-03-22 Gene gun DNA immunization of cattle induces humoral and CD4 T-cell-mediated immune responses against the Theileria parva polymorphic immunodominant molecule Fry, Lindsay M. Bastos, Reginaldo G. Stone, Brad C. Williams, Laura B. Knowles, Donald P. Murphy, Sean C. Vaccine Article Theileria parva kills over one million cattle annually in sub-Saharan Africa. Parasite genetic complexity, cellular response immunodominance, and bovine MHC diversity have precluded traditional vaccine development. One potential solution is gene gun (GG) immunization, which enables simultaneous administration of one or more DNA-encoded antigens. Although promising in murine, porcine, and human vaccination trials, bovine GG immunization studies are limited. We utilized the model T. parva antigen, polymorphic immunodominant molecule (PIM) to test bovine GG immunization. GG immunization using a mammalian codon optimized PIM sequence elicited significant anti-PIM antibody and cell-mediated responses in 7/8 steers, but there was no difference between immunized and control animals following T. parva challenge. The results suggest immunization with PIM, as delivered here, is insufficient to protect cattle from T. parva. Nonetheless, the robust immune responses elicited against this model antigen suggest GG immunization is a promising vaccine platform for T. parva and other bovine pathogens. Elsevier Science 2019-03-14 /pmc/articles/PMC6411927/ /pubmed/30782490 http://dx.doi.org/10.1016/j.vaccine.2019.02.009 Text en http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fry, Lindsay M.
Bastos, Reginaldo G.
Stone, Brad C.
Williams, Laura B.
Knowles, Donald P.
Murphy, Sean C.
Gene gun DNA immunization of cattle induces humoral and CD4 T-cell-mediated immune responses against the Theileria parva polymorphic immunodominant molecule
title Gene gun DNA immunization of cattle induces humoral and CD4 T-cell-mediated immune responses against the Theileria parva polymorphic immunodominant molecule
title_full Gene gun DNA immunization of cattle induces humoral and CD4 T-cell-mediated immune responses against the Theileria parva polymorphic immunodominant molecule
title_fullStr Gene gun DNA immunization of cattle induces humoral and CD4 T-cell-mediated immune responses against the Theileria parva polymorphic immunodominant molecule
title_full_unstemmed Gene gun DNA immunization of cattle induces humoral and CD4 T-cell-mediated immune responses against the Theileria parva polymorphic immunodominant molecule
title_short Gene gun DNA immunization of cattle induces humoral and CD4 T-cell-mediated immune responses against the Theileria parva polymorphic immunodominant molecule
title_sort gene gun dna immunization of cattle induces humoral and cd4 t-cell-mediated immune responses against the theileria parva polymorphic immunodominant molecule
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411927/
https://www.ncbi.nlm.nih.gov/pubmed/30782490
http://dx.doi.org/10.1016/j.vaccine.2019.02.009
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