Melioidosis Vaccines: A Systematic Review and Appraisal of the Potential to Exploit Biodefense Vaccines for Public Health Purposes

Charles Darwin University, Australia
PLoS Neglected Tropical Diseases (Impact Factor: 4.45). 01/2012; 6(1):e1488. DOI: 10.1371/journal.pntd.0001488
Source: PubMed


Burkholderia pseudomallei is a Category B select agent and the cause of melioidosis. Research funding for vaccine development has largely considered protection within the biothreat context, but the resulting vaccines could be applicable to populations who are at risk of naturally acquired melioidosis. Here, we discuss target populations for vaccination, consider the cost-benefit of different vaccination strategies and review potential vaccine candidates.
Melioidosis is highly endemic in Thailand and northern Australia, where a biodefense vaccine might be adopted for public health purposes. A cost-effectiveness analysis model was developed, which showed that a vaccine could be a cost-effective intervention in Thailand, particularly if used in high-risk populations such as diabetics. Cost-effectiveness was observed in a model in which only partial immunity was assumed. The review systematically summarized all melioidosis vaccine candidates and studies in animal models that had evaluated their protectiveness. Possible candidates included live attenuated, whole cell killed, sub-unit, plasmid DNA and dendritic cell vaccines. Live attenuated vaccines were not considered favorably because of possible reversion to virulence and hypothetical risk of latent infection, while the other candidates need further development and evaluation. Melioidosis is acquired by skin inoculation, inhalation and ingestion, but routes of animal inoculation in most published studies to date do not reflect all of this. We found a lack of studies using diabetic models, which will be central to any evaluation of a melioidosis vaccine for natural infection since diabetes is the most important risk factor.
Vaccines could represent one strand of a public health initiative to reduce the global incidence of melioidosis.


Available from: Gavin C K W Koh
  • Source
    • "Finally, chemical attachment of the sugar to the carrier protein can result in large and heterogeneous conjugates, modifying the native structure, and thus decreasing the protective nature of the vaccine. Both live attenuated and killed bacterial vaccines have been tested against B. pseudomallei, but provide little to no protection against disease and mortality in murine virulence models (Peacock et al., 2012). Additionally, since B. pseudomallei requires class III biosafety facilities, manufacturing glycoconjugates containing glycans from its native host is challenging and possibly hazardous. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Vaccines developing immune responses toward surface carbohydrates conjugated to proteins are effective in preventing infection and death by bacterial pathogens. Traditional production of these vaccines utilizes complex synthetic chemistry to acquire and conjugate the glycan to a protein. However, glycoproteins produced by bacterial protein glycosylation systems are significantly easier to produce, and could possible be used as vaccine candidates. In this work, we functionally expressed the Burkholderia pseudomallei O polysaccharide (OPS II), the Campylobacter jejuni oligosaccharyltransferase (OTase), and a suitable glycoprotein (AcrA) in a designer E. coli strain with a higher efficiency for production of glycoconjugates. We were able to produce and purify the OPS II-AcrA glycoconjugate, and MS analysis confirmed correct glycan was produced and attached. We observed the attachment of the O-acetylated deoxyhexose directly to the acceptor protein, which expands the range of substrates utilized by the OTase PglB. Injection of the glycoprotein into mice generated an IgG immune response against B. pseudomallei, and this response was partially protective against an intranasal challenge. Our experiments show that bacterial engineered glycoconjugates can be utilized as vaccine candidates against B. pseudomallei. Additionally, our new E. coli strain SDB1 is more efficient in glycoprotein production, and could have additional applications in the future.
    Frontiers in Microbiology 07/2014; 5(381). DOI:10.3389/fmicb.2014.00381 · 3.99 Impact Factor
  • Source
    • "B. pseudomallei is highly virulent via the aerosol route in a number of animal models [7–9], and because of these factors melioidosis is today regarded as an emerging infectious disease and is listed as a CDC tier 1 Select Agent. B. pseudomallei is highly refractory to antibiotic treatment [10], suggesting that vaccination might be the most effective way of controlling melioidosis [11]. Significant effort has been directed towards identifying and testing candidate vaccines, but thus far there are no candidates which are nearing licensure (reviewed by [12–14]). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei. It is refractory to antibiotic treatment and there is currently no licensed vaccine. In this report we detail the construction and protective efficacy of a polysaccharide-protein conjugate composed of B. pseudomallei lipopolysaccharide and the Hc fragment of tetanus toxin. Immunisation of mice with the lipopolysaccharide-conjugate led to significantly reduced bacterial burdens in the spleen 48 hours after challenge and afforded significant protection against a lethal challenge with B. pseudomallei. The conjugate generated significantly higher levels of antigen-specific IgG1 and IgG2a than in lipopolysaccharide-immunised mice. Immunisation with the conjugate also demonstrated a bias towards Th1 type responses, evidenced by high levels of IgG2a. In contrast, immunisation with unconjugated lipopolysaccharide evoked almost no IgG2a demonstrating a bias towards Th2 type responses. This study demonstrates the effectiveness of this approach in the development of an efficacious and protective vaccine against melioidosis.
    Research Journal of Immunology 05/2014; 2014:392170. DOI:10.1155/2014/392170
  • Source
    • "However, during the late stages of infection, antigen-specific T cells, mainly CD4+ T cells producing IFN-γ are essential for protection [8], [14], [15]. Some of these IFN-γ+CD4+ T cells have demonstrated the capacity to respond to specific B. pseudomallei proteins in mice and in humans [8], [9], [16], [17], [18], [19]. It has been suggested that the main function of IFN-γ is activation of macrophages, however the exact mechanism(s) involved in the production of IFN-γ during the infection or why there is incomplete protection against this pathogen are still unknown. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Melioidosis is a disease in tropical and subtropical regions of the world that is caused by Burkholderia pseudomallei. In endemic regions the disease occurs primarily in humans and goats. In the present study, we used the goat as a model to dissect the polar lipids of B. pseudomallei to identify lipid molecules that could be used for adjuvants/vaccines or as diagnostic tools. We showed that the lipidome of B. pseudomallei and its fractions contain several polar lipids with the capacity to elicit different immune responses in goats, namely rhamnolipids and ornithine lipids which induced IFN-γ, whereas phospholipids and an undefined polar lipid induced strong IL-10 secretion in CD4(+) T cells. Autologous T cells co-cultured with caprine dendritic cells (cDCs) and polar lipids of B. pseudomallei proliferated and up-regulated the expression of CD25 (IL-2 receptor) molecules. Furthermore, we demonstrated that polar lipids were able to up-regulate CD1w2 antigen expression in cDCs derived from peripheral blood monocytes. Interestingly, the same polar lipids had only little effect on the expression of MHC class II DR antigens in the same caprine dendritic cells. Finally, antibody blocking of the CD1w2 molecules on cDCs resulted in decreased expression for IFN-γ by CD4(+) T cells. Altogether, these results showed that polar lipids of B. pseudomallei are recognized by the caprine immune system and that their recognition is primarily mediated by the CD1 antigen cluster.
    PLoS ONE 11/2013; 8(11):e80368. DOI:10.1371/journal.pone.0080368 · 3.23 Impact Factor
Show more