Abstract
BackgroundWe have previously demonstrated protective efficacy against B. melitensis using formulations of naked DNA vaccines encoding genes ialB and omp25. The present study was undertaken to further understand the immune response generated by the protective vaccination regimens and to evaluate cationic liposome adsorption as a delivery method to improve vaccine utility.MethodsThe protective efficacy and immunogenicity of vaccines delivered as four doses of naked DNA, a single dose of naked DNA or a single dose of DNA surface adsorbed to cationic liposomes were compared using the BALB/c murine infection model of B. melitensis. Antigen-specific T cells and antibody responses were compared between the various formulations.ResultsThe four dose vaccination strategy was confirmed to be protective against B. melitensis challenge. The immune response elicited by the various vaccines was found to be dependent upon both the antigen and the delivery strategy, with the IalB antigen favouring CD4+ T cell priming and Omp25 antigen favouring CD8+. Delivery of the p-ialB construct as a lipoplex improved antibody generation in comparison to the equivalent quantity of naked DNA. Delivery of p-omp25 as a lipoplex altered the profile of responsive T cells from CD8+ to CD4+ dominated. Under these conditions neither candidate delivered by single dose naked DNA or lipoplex vaccination methods was able to produce a robust protective effect.ConclusionsDelivery of the p-omp25 and p-ialB DNA vaccine candidates as a lipoplex was able to enhance antibody production and effect CD4+ T cell priming, but was insufficient to promote protection from a single dose of either vaccine. The enhancement of immunogenicity by lipoplex delivery is a promising step toward improving the practicality of these two candidate vaccines, and suggests that this lipoplex formulation may be of value in situations where improvements to CD4+ responses are required. However, in the case of Brucella vaccine development it is suggested that further modifications to the candidate vaccines and delivery strategies will be required in order to deliver sustained protection.
Highlights
We have previously demonstrated protective efficacy against B. melitensis using formulations of naked DNA vaccines encoding genes ialB and omp25
Whilst Great Britain and a large proportion of the developed world are designated as Officially Brucella Free (OBF), a considerable number of countries remain endemic for this debilitating zoonosis
In conclusion, our study has demonstrated an improvement in humoral immunity through delivery of the plasmids surface adsorbed to cationic liposomes
Summary
We have previously demonstrated protective efficacy against B. melitensis using formulations of naked DNA vaccines encoding genes ialB and omp. Brucellosis is a worldwide zoonosis of considerable social and economic importance. The disease is largely considered to be an occupational zoonosis as natural human infection is acquired through direct contact with the organism and most usually associated with contact with infected animals or animal products. Brucellosis is one of the most frequently reported laboratory acquired bacterial infections and Brucella spp., are considered potential biothreat agents (For review [1]). Whilst Great Britain and a large proportion of the developed world are designated as Officially Brucella Free (OBF), a considerable number of countries remain endemic for this debilitating zoonosis. Sheep and goat brucellosis caused by Brucella melitensis is an intractable problem in large areas of the Mediterranean basin and Near East, and is the cause of significant economic livestock industry losses and human morbidity
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