A DNA vaccination regime including protein boost and electroporation protects cattle against foot-and-mouth disease

作者:Fowler V*; Robinson L; Bankowski B; Cox S; Parida S; Lawlor C; Gibson D; O' Brien F; Ellefsen B; Hannaman D; Takamatsu H H; Barnett P V
来源:Antiviral Research, 2012, 94(1): 25-34.
DOI:10.1016/j.antivira1.2012.02.002

摘要

Protection against foot-and-mouth disease (FMD) using DNA technology has been documented for sheep and pigs but not for the highly susceptible species of cattle. %26lt;br%26gt;Twenty-five Holstein Friesian cross-bred cattle were vaccinated twice, 21 days apart, with a DNA vaccine containing the capsid coding region (P1) along with the non-structural proteins 2A, 3C and 3D (pcDNA3.1/P1-2A3C3D) of O-1 Kaufbeuren alone or coated onto PLG (D,L-lactide-co-glycolide) microparticles. In some pcDNA3.1/P1-2A3C3D was also combined with an adjuvant plasmid expressing bovine granulocyte macrophage colony stimulating factor (GM-CSF). DNA vaccinations were administered intramuscularly with, or without, the use of electroporation and at 42 days post primary vaccination cattle received a protein boost of 146S FMD virus (FMDV) antigen and non-structural protein 3D. For comparison, four cattle were vaccinated with a conventional FMD vaccine and two more included as unvaccinated controls. Apart from those immunised with PLC microparticles all cattle were challenged with 10(5) TCID50 cattle adapted O-1 Lausanne FMDV virus at day 93 post primary vaccination. %26lt;br%26gt;All DNA vaccinated cattle regardless of regime developed good humoral and cell mediated responses prior to challenge. The best overall virus neutralising antibody, IFN-gamma and clinical protection (75%) were seen in the cattle whereby the DNA was delivered by electroporation. In contrast, only 25% of cattle vaccinated with the DNA vaccine without electroporation were clinically protected. The addition of GM-CSF in combination with electroporation further improved the efficacy of the vaccine, as demonstrated from the reduction of clinical disease and virus excretions in nasal swabs. %26lt;br%26gt;We thus demonstrate for the first time that cattle can be clinically protected against FMDV challenge following a DNA prime-protein boost strategy, and particularly when DNA vaccine is combined with GM-CSF and delivered by electroporation.

  • 出版日期2012-4