Melioidosis: Where Do We Stand in the Development of an Effective Vaccine?

Muruato, Laura A.; Torres, Alfredo G.

doi:10.2217/fmb-2015-0018

Cited by 7 publications

(6 citation statements)

References 15 publications

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“…No melioidosis vaccine is currently available for human use; some vaccine candidates have been shown to provide partial protection against melioidosis or glanders in murine models of infection 212,214,215 , but few have been tested in non-human primates or humans 216 . Live attenuated vaccines induce a more-comprehensive immune response in animal models and are currently considered the best approach for generating protection against B. pseudomallei infection 16,217 . However, subunit-based vaccines provide a feasible alternative because of their increased safety and potential for large-scale production.…”

Section: Discussionmentioning

confidence: 99%

“…However, subunit-based vaccines provide a feasible alternative because of their increased safety and potential for large-scale production. Experimental evidence indicates that the combination of bacterial polysaccharides (LPSs or other capsular polysaccharides) with well-defined protein antigens (glycoconjugates) can generate substantial protection against Burkholderia infections 217 . This rapid advancement in vaccine design and optimization is very promising, and several vaccine candidates are currently being tested.…”

Section: Discussionmentioning

confidence: 99%

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Melioidosis

Wiersinga

Virk

Torres

et al. 2018

Nat Rev Dis Primers

505

792

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Burkholderia pseudomallei is a Gram-negative environmental bacterium and the aetiological agent of melioidosis, a life-threatening infection that is estimated to account for ∼89,000 deaths per year worldwide. Diabetes mellitus is a major risk factor for melioidosis, and the global diabetes pandemic could increase the number of fatalities caused by melioidosis. Melioidosis is endemic across tropical areas, especially in southeast Asia and northern Australia. Disease manifestations can range from acute septicaemia to chronic infection, as the facultative intracellular lifestyle and virulence factors of B. pseudomallei promote survival and persistence of the pathogen within a broad range of cells, and the bacteria can manipulate the host's immune responses and signalling pathways to escape surveillance. The majority of patients present with sepsis, but specific clinical presentations and their severity vary depending on the route of bacterial entry (skin penetration, inhalation or ingestion), host immune function and bacterial strain and load. Diagnosis is based on clinical and epidemiological features as well as bacterial culture. Treatment requires long-term intravenous and oral antibiotic courses. Delays in treatment due to difficulties in clinical recognition and laboratory diagnosis often lead to poor outcomes and mortality can exceed 40% in some regions. Research into B. pseudomallei is increasing, owing to the biothreat potential of this pathogen and increasing awareness of the disease and its burden; however, better diagnostic tests are needed to improve early confirmation of diagnosis, which would enable better therapeutic efficacy and survival.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Melioidosis

Wiersinga

Virk

Torres

et al. 2018

Nat Rev Dis Primers

505

792

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“…8 Applying this concept to melioidosis, northeast Thailand is a highly endemic region. 11,12 However, validation of the abilities of vaccine antigen candidates for boosting human immune responses for post-exposure vaccination in vivo is lacking. 9 Although, immunological memory is not sufficient for complete protection, boosting protective immunity in seropositive people in endemic areas may be considered.…”

Section: Introductionmentioning

confidence: 99%

“…5,8,10 To date, several vaccine antigen candidates have been identified and tested for in vivo protection in murine models of pre-exposure vaccination. 11,12 However, validation of the abilities of vaccine antigen candidates for boosting human immune responses for post-exposure vaccination in vivo is lacking.…”

Section: Introductionmentioning

confidence: 99%

Boosting of post‐exposure human T‐cell and B‐cell recall responses in vivo by Burkholderia pseudomallei‐related proteins

et al. 2017

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Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease with high incidence and mortality in South East Asia and northern Australia. To date there is no protective vaccine and antibiotic treatment is prolonged and not always effective. Most people living in endemic areas have been exposed to the bacteria and have developed some immunity, which may have helped to prevent disease. Here, we used a humanized mouse model (hu-PBL-SCID), reconstituted with human peripheral blood mononuclear cells from seropositive donors, to illustrate the potential of three known antigens (FliC, OmpA and N-PilO2) for boosting both T-cell and B-cell immune responses. All three antigens boosted the production of specific antibodies in vivo, and increased the number of antibody and interferon-γ-secreting cells, and induced antibody affinity maturation. Moreover, antigen-specific antibodies isolated from either seropositive individuals or boosted mice, were found to enhance phagocytosis and oxidative burst activities from human polymorphonuclear cells. Our study demonstrates that FliC, OmpA and N-PilO2 can stimulate human memory T and B cells and highlight the potential of the hu-PBL-SCID system for screening and evaluation of novel protein antigens for inclusion in future vaccine trials against melioidosis.

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“…Furthermore, T6SS-1 is critical for multinucleated giant cell (MNGC) formation. Finally, the role of exotoxins as a major virulence factor has not been demonstrated during infection in any validated model of infection and the endotoxin LPS is not considered a major virulence factor, and it is a common component of vaccine candidates [38]. Of interest, the authors state that the LPS of B .…”

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confidence: 99%