Elsevier

Vaccine

Volume 35, Issue 44, 20 October 2017, Pages 5981-5989
Vaccine

Burkholderia pseudomallei and Burkholderia mallei vaccines: Are we close to clinical trials?

https://doi.org/10.1016/j.vaccine.2017.03.022Get rights and content

Abstract

B. pseudomallei is the cause of melioidosis, a serious an often fatal disease of humans and animals. The closely related bacterium B. mallei, which cases glanders, is considered to be a clonal derivative of B. pseudomallei. Both B. pseudomallei and B. mallei were evaluated by the United States and the former USSR as potential bioweapons. Much of the effort to devise biodefence vaccines in the past decade has been directed towards the identification and formulation of sub-unit vaccines which could protect against both melioidosis and glanders. A wide range of proteins and polysaccharides have been identified which protective immunity in mice. In this review we highlight the significant progress that has been made in developing glycoconjugates as sub-unit vaccines. We also consider some of the important the criteria for licensing, including the suitability of the “animal rule” for assessing vaccine efficacy, the protection required from a vaccine and the how correlates of protection will be identified. Vaccines developed for biodefence purposes could also be used in regions of the world where naturally occurring disease is endemic.

Section snippets

Melioidosis; The global incidence

B. pseudomallei is the cause of melioidosis, a serious and often fatal disease of humans and animals. The closely related bacterium B. mallei, which causes glanders, is a clonal derivative of B. pseudomallei [1], with a reduced host range. In this review we have included references to B. mallei where appropriate. Human melioidosis can range from a localised skin infection to an acute septicaemia or a pneumonia. Some individuals develop chronic disease, whilst others apparently clear the

Live attenuated vaccines

A range of attenuated B. pseudomallei (and B. mallei) mutants able to induce protective immunity in mice have been reported [14], [20], [21], [22], [23], [24], [25], [26]. However, not all attenuated mutants can induce protective immunity. Some are over-attenuated and are cleared too rapidly or the disrupted gene may play a role in biosynthesis of a protective antigen [27]. Immunisation with Burkholderia thailandensis, a naturally attenuated species that is related to B. pseudomallei can induce

Criteria for candidate selection

An efficacious melioidosis/glanders vaccine would ideally provide high level protection against multiple routes of infection, protect against multiple LPS types and provide sterilizing immunity. Additionally, it would be both safe and cost-effective to produce. At present, some of the most promising vaccine candidates undergoing pre-clinical evaluation include LPS- and CPS-based glycoconjugates, protein sub-units, OMVs and live attenuated strains. Important properties associated with these

Correlates of protection

All vaccine discovery and evaluation projects benefit from an understanding of the immune responses underlying protection. The term ‘immunological correlates of protection’ describes an immunological response, typically measured by laboratory assay, which is statistically associated with vaccine efficacy and based on clinical trial data in humans [85], [86]. Correlates of protection may be mechanistic, where the response measured directly mediates protection, or non-mechanistic serving as an

Conclusion

There have been a number of important developments since the publication of previous reviews on the development of B. pseudomallei and B. mallei vaccines. In this review we highlight the DTRA guidelines on vaccine performance, and which might drive any assessment of the candidates which could be selected for development and clinical trials. These criteria might be equally applicable to vaccines for biodefence and public health purposes. We also consider some of the important the criteria for

References (111)

  • R.G. Swetha et al.

    Identification of CD4+ T-cell epitope and investigation of HLA distribution for the immunogenic proteins of Burkholderia pseudomallei using in silico approaches - A key vaccine development strategy for melioidosis

    J Theor Biol

    (2016)
  • L.J. Gourlay et al.

    Exploiting the Burkholderia pseudomallei acute phase antigen BPSL2765 for structure-based epitope discovery/design in structural vaccinology

    Chem Biol

    (2013)
  • Y.S. Chen et al.

    Immunogenicity and anti-Burkholderia pseudomallei activity in Balb/c mice immunized with plasmid DNA encoding flagellin

    Vaccine

    (2006)
  • C. Heiss et al.

    Revised structures for the predominant O-polysaccharides expressed by Burkholderia pseudomallei and Burkholderia mallei

    Carbohyd Res

    (2013)
  • S.A. Ngugi et al.

    Lipopolysaccharide from Burkholderia thailandensis E264 provides protection in a murine model of melioidosis

    Vaccine

    (2010)
  • A.E. Gregory et al.

    A gold nanoparticle-linked glycoconjugate vaccine against Burkholderia mallei

    Nanomedicine

    (2015)
  • A.G. Torres et al.

    Protection of non-human primates against glanders with a gold nanoparticle glycoconjugate vaccine

    Vaccine

    (2015)
  • A.E. Scott et al.

    Protection against experimental melioidosis with a synthetic manno-heptopyranose hexasaccharide glycoconjugate

    Bioconj Chem

    (2016)
  • R.W. Titball

    Vaccines against intracellular bacterial pathogens

    Drug Discov Today

    (2008)
  • A. Thakur et al.

    Immune markers and correlates of protection for vaccine induced immune responses

    Vaccine

    (2012)
  • A.J. Jacobs et al.

    Antibodies and tuberculosis

    Tuberculosis

    (2016)
  • R. Tanner et al.

    In vitro mycobacterial growth inhibition assays: a tool for the assessment of protective immunity and evaluation of tuberculosis vaccine efficacy

    Vaccine

    (2016)
  • S.G. Smith et al.

    Polyfunctional CD4 T-cells correlate with in vitro mycobacterial growth inhibition following Mycobacterium bovis BCG-vaccination of infants

    Vaccine

    (2016)
  • W.C. Nierman et al.

    Structural flexibility in the Burkholderia mallei genome

    Proc Natl Acad Sci USA

    (2004)
  • D. Limmathurotsakul et al.

    Melioidosis: a clinical overview

    Br Med Bull

    (2011)
  • W.J. Wiersinga et al.

    Melioidosis

    N Engl J Med

    (2012)
  • K. Alibek et al.

    Biohazard: the chilling true story of the largest covert biological weapons program in the world, told from the inside by the man who ran it

    (1999)
  • J.E.V.C. Moon

    US biological warfare planning and preparedness: the dilemmas of policy

  • C. Howe et al.

    The pseudomallei group: a review

    J Infect Dis

    (1971)
  • D. Limmathurotsakul et al.

    Increasing incidence of human melioidosis in Northeast Thailand

    Am J Trop Med Hyg

    (2010)
  • A.C. Cheng et al.

    Melioidosis: epidemiology, pathophysiology and management

    Clin Microbiol Rev

    (2005)
  • Y. Suputtamongkol et al.

    Risk factors for melioidosis and bacteremic melioidosis

    Clin Infect Dis

    (1999)
  • D. Limmathurotsakul et al.

    Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis

    Nat Microbiol

    (2016)
  • D.A. Moustafa et al.

    Recombinant Salmonella expressing Burkholderia mallei LPS O antigen provides protection in a murine model of melioidosis and glanders

    PLoS ONE

    (2015)
  • T.M. Mott et al.

    Characterization of the Burkholderia mallei tonb mutant and its potential as a backbone strain for vaccine development

    PLoS Negl Trop Dis

    (2015)
  • S. Zhang et al.

    In vitro and in vivo studies on monoclonal antibodies with prominent bactericidal activity against Burkholderia pseudomallei and Burkholderia mallei

    Clin Vaccine Immunol

    (2011)
  • M.A. Schell et al.

    Outer membrane proteome of Burkholderia pseudomallei and Burkholderia mallei from diverse growth conditions

    J Proteome Res

    (2011)
  • G.C. Whitlock et al.

    Protective response to subunit vaccination against intranasal Burkholderia mallei and B. pseudomallei challenge

    Procedia Vaccinol

    (2010)
  • M.H. Norris et al.

    The Burkholderia pseudomallei Deltaasd mutant exhibits attenuated intracellular infectivity and imparts protection against acute inhalation melioidosis in mice

    Infect Immun

    (2011)
  • T. Srilunchang et al.

    Construction and characterization of an unmarked aroC deletion mutant of Burkholderia pseudomallei strain A2

    Southeast Asian J Trop Med Public Health

    (2009)
  • M.G. Moule et al.

    Characterization of new virulence factors involved in the intracellular growth and survival of Burkholderia pseudomallei

    Infect Immun

    (2015)
  • C.L. Hatcher et al.

    Burkholderia mallei clh001 attenuated vaccine strain is immunogenic and protects against acute respiratory glanders

    Infect Immun

    (2016)
  • C.M. Muller et al.

    Role of RelA and SpoT in Burkholderia pseudomallei virulence and immunity

    Infect Immun

    (2012)
  • T.P. Atkins et al.

    Characterisation of an acapsular mutant of Burkholderia pseudomallei identified by signature tagged mutagenesis

    J Med Microbiol

    (2002)
  • A.E. Scott et al.

    Protection against experimental melioidosis following immunization with live Burkholderia thailandensis expressing a manno-heptose capsule

    Clin Vaccine Immunol

    (2013)
  • E.B. Silva et al.

    Correlates of immune protection following cutaneous immunization with an attenuated Burkholderia pseudomallei vaccine

    Infect Immun

    (2013)
  • K.L. Propst et al.

    A Burkholderia pseudomallei deltapurM mutant is avirulent in immunocompetent and immunodeficient animals: candidate strain for exclusion from select-agent lists

    Infect Immun

    (2010)
  • E.B. Silva et al.

    Development of Burkholderia mallei and pseudomallei vaccines

    Front Cell Infect Microbiol

    (2013)
  • S.J. Peacock et al.

    Melioidosis vaccines: a systematic review and appraisal of the potential to exploit biodefense vaccines for public health purposes

    PLoS Negl Trop Dis

    (2012)
  • D. Limmathurotsakul et al.

    Consensus on the development of vaccines against naturally acquired melioidosis

    Emerg Infect Dis

    (2015)
  • Cited by (63)

    • Comprehensive approaches for the detection of Burkholderia pseudomallei and diagnosis of melioidosis in human and environmental samples

      2022, Microbial Pathogenesis
      Citation Excerpt :

      This vaccine may be produced at low cost and function similarly with live-attenuated vaccines to induce immunity via multiple antigens presented. It is different with subunit vaccines which contain only single antigen [125]. Significant protection in the host has been demonstrated by using paraformaldehyde-killed B. pseudomallei [126].

    View all citing articles on Scopus
    View full text