Investigation of dendritic cells as a vector for vaccine delivery

Healey, Gareth D. (2005). Investigation of dendritic cells as a vector for vaccine delivery. PhD thesis The Open University.



Dendritic cells (DC) are an attractive target for both vaccine targeting and use as a delivery vehicle due to their ability to direct innate and adaptive immune responses. In this study a procedure was developed where DC were employed as a vehicle to induce cell-mediated immune responses to the Gram negative bacillus Burkholderia pseudomallei. This bacterium is the causative agent of melioidosis, a disease endemicto areas of south-east Asia and northern Australia, to which presently no licensed vaccine exists.

Purified DC were pulsed with heat-killed (HK) whole cell B. pseudomallei and used to immunise syngeneic mice. The use of this immunisation method elicited strong cellular immune responses against B. pseudomallei, which have historically been difficult to generate. Antibody responses following immunisation with DC were low. Booster immunisations of either a second dose of HK B. pseudomallei pulsed DC or HK B.pseudomallei in MPL + TDM adjuvant were administered to increase the immuneresponse. Immunised animals were challenged with fully virulent B. pseudomallei and protection was demonstrated in animals immunised with a combination of HK B. pseudomallei pulsed DC and HK B. pseudomallei delivered in MPL + TDM adjuvant. The protective immune response demonstrated was then further elucidated to reveal arole for both cell-mediated and humoral immunity in protection against B. pseudomallei infection. The data also demonstrate the potential for DC as vaccine delivery vectors and as a screening mechanism for the evaluation of potential vaccine candidates.

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