Progress toward development of vaccines against melioidosis: A review

Abstract

Background: Melioidosis is a serious and often fatal disease that is prevalent in subtropical and tropical climates, primarily in at-risk groups (eg, those with diabetes, alcoholism, or other cause of immunosuppression). Treatment is often unsuccessful, with infection frequently relapsing. Burkholderia pseudomallei, the etiologic agent of melioidosis, is inherently resistant to many antibiotics.

Objective: This article reviews available evidence on the development of vaccines against melioidosis, including live attenuated vaccines, inactivated whole cell vaccines, and recombinant subunit vaccines.

Methods: Web of Science and PubMed (1950-February 2010) were searched for relevant reports using the term Burkholderia pseudomallei alone and combined with live attenuated vaccine, inactivated vaccine, animal models, and immunity. The reference lists of identified articles were reviewed for additional relevant publications.

Results: Studies in murine models suggest that protective immunity against B pseudomallei may be induced by a range of living and nonliving immunogens. The strongest protective immunity was induced by live attenuated immunogens, although concerns about latency make it unlikely that such vaccines will be appropriate for use in humans. Heat-inactivated immunogens have shown promise, and several candidates for subunit vaccines have been tested. However, in all cases, it has been difficult to achieve induction of sterile immunity and protection against airborne infection.

Conclusions: Live attenuated mutants of B pseudomallei have been found to be the most effective immunogens in mice, although it is unlikely that such mutants would be appropriate for a vaccine against melioidosis in humans. The ongoing challenge is to identify nonliving formulations that are able to induce good protective immunity. Both humoral and cell-mediated immunity are likely to be required. In this respect, naked DNA vaccines have the potential to provide high-level protection.