Investigation of dendritic cells as a vector for vaccine delivery

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 <i>Burkholderia pseudomallei</i>. 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.<br></br><br></br>Purified DC were pulsed with heat-killed (HK) whole cell <i>B. pseudomallei</i> and used to immunise syngeneic mice. The use of this immunisation method elicited strong cellular immune responses against <i>B. pseudomallei</i>, which have historically been difficult to generate. Antibody responses following immunisation with DC were low. Booster immunisations of either a second dose of HK <i>B. pseudomallei</i> pulsed DC or HK <i>B.pseudomallei</i> in MPL + TDM adjuvant were administered to increase the immuneresponse. Immunised animals were challenged with fully virulent <i>B. pseudomallei</i> and protection was demonstrated in animals immunised with a combination of HK <i>B. pseudomallei</i> pulsed DC and HK <i>B. pseudomallei</i> 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 <i>B. pseudomallei</i> 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.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

The Open University

Year dc:date.issued

2005

Author dc:creator

• Healey, Gareth D.

Language dc:language

en