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Development of Burkholderia mallei and pseudomallei vaccines.

Abstract

Burkholderia mallei and Burkholderia pseudomallei are Gram-negative bacteria that cause glanders and melioidosis, respectively. Inhalational infection with either organism can result in severe and rapidly fatal pneumonia. Inoculation by the oral and cutaneous routes can also produce infection. Chronic infection may develop after recovery from acute infection with both agents, and control of infection with antibiotics requires prolonged treatment. Symptoms for both meliodosis and glanders are non-specific, making diagnosis difficult. B. pseudomallei can be located in the environment, but in the host, B. mallei and B. psedomallei are intracellular organisms, and infection results in similar immune responses to both agents. Effective early innate immune responses are critical to controlling the early phase of the infection. Innate immune signaling molecules such as TLR, NOD, MyD88, and pro-inflammatory cytokines such as IFN-γ and TNF-α play key roles in regulating control of infection. Neutrophils and monocytes are critical cells in the early infection for both microorganisms. Both monocytes and macrophages are necessary for limiting dissemination of B. pseudomallei. In contrast, the role of adaptive immune responses in controlling Burkholderia infection is less well understood. However, T cell responses are critical for vaccine protection from Burkholderia infection. At present, effective vaccines for prevention of glanders or meliodosis have not been developed, although recently development of Burkholderia vaccines has received renewed attention. This review will summarize current and past approaches to develop B. mallei and B. pseudomalllei vaccines, with emphasis on immune mechanisms of protection and the challenges facing the field. At present, immunization with live attenuated bacteria provides the most effective and durable immunity, and it is important therefore to understand the immune correlates of protection induced by live attenuated vaccines. Subunit vaccines have typically provided less robust immunity, but are safer to administer to a wider variety of people, including immune compromised individuals because they do not reactivate or cause disease. The challenges facing B. mallei and B. pseudomalllei vaccine development include identification of broadly protective antigens, design of efficient vaccine delivery and adjuvant systems, and a better understanding of the correlates of protection from both acute and chronic infection.

Authors+Show Affiliations

Department of Microbiology, Immunology, and Pathology, Regional Center of Excellence in Emerging Diseases and Bioterrorism, Colorado State University Ft. Collins, CO, USA.No affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

23508691

Citation

Silva, Ediane B., and Steven W. Dow. "Development of Burkholderia Mallei and Pseudomallei Vaccines." Frontiers in Cellular and Infection Microbiology, vol. 3, 2013, p. 10.
Silva EB, Dow SW. Development of Burkholderia mallei and pseudomallei vaccines. Front Cell Infect Microbiol. 2013;3:10.
Silva, E. B., & Dow, S. W. (2013). Development of Burkholderia mallei and pseudomallei vaccines. Frontiers in Cellular and Infection Microbiology, 3, 10. https://doi.org/10.3389/fcimb.2013.00010
Silva EB, Dow SW. Development of Burkholderia Mallei and Pseudomallei Vaccines. Front Cell Infect Microbiol. 2013;3:10. PubMed PMID: 23508691.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development of Burkholderia mallei and pseudomallei vaccines. AU - Silva,Ediane B, AU - Dow,Steven W, Y1 - 2013/03/11/ PY - 2012/08/28/received PY - 2013/02/20/accepted PY - 2013/3/20/entrez PY - 2013/3/20/pubmed PY - 2013/8/29/medline KW - Burkholderia KW - glanders KW - immune response KW - live attenuated KW - melioidosis KW - vaccine SP - 10 EP - 10 JF - Frontiers in cellular and infection microbiology JO - Front Cell Infect Microbiol VL - 3 N2 - Burkholderia mallei and Burkholderia pseudomallei are Gram-negative bacteria that cause glanders and melioidosis, respectively. Inhalational infection with either organism can result in severe and rapidly fatal pneumonia. Inoculation by the oral and cutaneous routes can also produce infection. Chronic infection may develop after recovery from acute infection with both agents, and control of infection with antibiotics requires prolonged treatment. Symptoms for both meliodosis and glanders are non-specific, making diagnosis difficult. B. pseudomallei can be located in the environment, but in the host, B. mallei and B. psedomallei are intracellular organisms, and infection results in similar immune responses to both agents. Effective early innate immune responses are critical to controlling the early phase of the infection. Innate immune signaling molecules such as TLR, NOD, MyD88, and pro-inflammatory cytokines such as IFN-γ and TNF-α play key roles in regulating control of infection. Neutrophils and monocytes are critical cells in the early infection for both microorganisms. Both monocytes and macrophages are necessary for limiting dissemination of B. pseudomallei. In contrast, the role of adaptive immune responses in controlling Burkholderia infection is less well understood. However, T cell responses are critical for vaccine protection from Burkholderia infection. At present, effective vaccines for prevention of glanders or meliodosis have not been developed, although recently development of Burkholderia vaccines has received renewed attention. This review will summarize current and past approaches to develop B. mallei and B. pseudomalllei vaccines, with emphasis on immune mechanisms of protection and the challenges facing the field. At present, immunization with live attenuated bacteria provides the most effective and durable immunity, and it is important therefore to understand the immune correlates of protection induced by live attenuated vaccines. Subunit vaccines have typically provided less robust immunity, but are safer to administer to a wider variety of people, including immune compromised individuals because they do not reactivate or cause disease. The challenges facing B. mallei and B. pseudomalllei vaccine development include identification of broadly protective antigens, design of efficient vaccine delivery and adjuvant systems, and a better understanding of the correlates of protection from both acute and chronic infection. SN - 2235-2988 UR - https://www.unboundmedicine.com/medline/citation/23508691/Development_of_Burkholderia_mallei_and_pseudomallei_vaccines_ L2 - https://doi.org/10.3389/fcimb.2013.00010 DB - PRIME DP - Unbound Medicine ER -