Multicomponent gold nano-glycoconjugate as a highly immunogenic and protective platform against Burkholderia mallei.
Abstract: Burkholderia mallei (Bm) is a facultative intracellular pathogen and the etiological agent of glanders, a highly infectious zoonotic disease occurring in equines and humans. The intrinsic resistance to antibiotics, lack of specific therapy, high mortality, and history as a biothreat agent, prompt the need of a safe and effective vaccine. However, the limited knowledge of protective Bm-specific antigens has hampered the development of a vaccine. Further, the use of antigen-delivery systems that enhance antigen immunogenicity and elicit robust antigen-specific immune responses has been limited and could improve vaccines against Bm. Nanovaccines, in particular gold nanoparticles (AuNPs), have been investigated as a strategy to broaden the repertoire of vaccine-mediated immunity and as a tool to produce multivalent vaccines. To synthesize a nano-glycoconjugate vaccine, six predicted highly immunogenic antigens identified by a genome-wide bio- and immuno-informatic analysis were purified and coupled to AuNPs along with lipopolysaccharide (LPS) from B. thailandensis. Mice immunized intranasally with individual AuNP-protein-LPS conjugates, showed variable degrees of protection against intranasal Bm infection, while an optimized combination formulation (containing protein antigens OmpW, OpcP, and Hemagglutinin, along with LPS) showed complete protection against lethality in a mouse model of inhalational glanders. Animals immunized with different nano-glycoconjugates showed robust antigen-specific antibody responses. Moreover, serum from animals immunized with the optimized nano-glycoconjugate formulation showed sustained antibody responses with increased serum-mediated inhibition of adherence and opsonophagocytic activity in vitro. This study provides the basis for the rational design and construction of a multicomponent vaccine platform against Bm.
© The Author(s) 2020.
Publication Date: 2020-09-10 PubMed ID: 32963813PubMed Central: PMC7483444DOI: 10.1038/s41541-020-00229-9Google Scholar: Lookup
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- Journal Article
Summary
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The research article discusses the development of a highly potent and protective vaccine against Burkholderia mallei, a bacteria causing the severe zoonotic disease glanders, by coupling its immunogenic antigens with gold nanoparticles (AuNPs).
Objectives and Background of the Study
- The main aim of the study was to find an efficient solution against Burkholderia mallei, a bacteria causing glanders, a highly infectious zoonotic disease occurring in equines and humans. The bacteria’s inherent resistance to antibiotics, high mortality, and its history as a biological threat necessitate the need for a robust vaccine. However, the limited knowledge about its specific antigens has been a challenge to vaccine development.
- Moreover, the research highlights the limited use of antigen-delivery systems that can enhance the immunogenicity of the antigens and produce a robust antigen-specific immune response.
Research Process and Findings
- The researchers utilized a strategy of combining immunogenic antigens with nanoparticles, specifically gold nanoparticles (AuNPs), to construct a highly effective vaccine. They picked six highly immunogenic antigens identified via genome-wide bio- and immuno-informatic analysis and coupled them to AuNPs with the lipopolysaccharide (LPS) from Burkholderia mallei.
- Further, the vaccine was tested on mice who were immunized intranasally. The results showed variable degrees of protection against the disease.
- An optimized version with protein antigens OmpW, OpcP, and Hemagglutinin combined with LPS demonstrated complete protection against lethality in a mouse model for inhalational glanders, highlighting the high effectiveness of the vaccine.
Outcome of the Study
- The mice immunized with different nano-glycoconjugates displayed strong antigen-specific antibody responses, proving the potential of the vaccine.
- Additionally, serum from animals immunized with the optimized nano-glycoconjugate formulation showed sustained antibody responses and increased serum-mediated inhibition of adherence and opsonophagocytic activity in vitro.
- The study offers valuable insights for the design and construction of a multicomponent vaccine strategy against Burkholderia mallei. It acts as a foundation for creating vaccines, not just for this particular disease but potentially for others as well where the pathogen’s specific antigen is a challenge.
Cite This Article
APA
Tapia D, Sanchez-Villamil JI, Torres AG.
(2020).
Multicomponent gold nano-glycoconjugate as a highly immunogenic and protective platform against Burkholderia mallei.
NPJ Vaccines, 5, 82.
https://doi.org/10.1038/s41541-020-00229-9 Publication
Researcher Affiliations
- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77550 USA.
- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77550 USA.
- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77550 USA.
- Department of Pathology, University of Texas Medical Branch, Galveston, TX 77550 USA.
Grant Funding
- R01 AI126601 / NIAID NIH HHS
Conflict of Interest Statement
Competing interestsThe authors declare no competing interests.
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Citations
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