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Published on: February 24, 2023
Burkholderia pseudomallei capsular polysaccharide conjugates provide protection against acute melioidosis
Andrew E Scott1, Mary N Burtnick2, Margaret G M Stokes3
1Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom aescott2@dstl.gov.uk.
Abstract:
Burkholderia pseudomallei, the etiologic agent of melioidosis, is a CDC tier 1 select agent that causes severe disease in both humans and animals. Diagnosis and treatment of melioidosis can be challenging, and in the absence of optimal chemotherapeutic intervention, acute disease is frequently fatal. Melioidosis is an emerging infectious disease for which there are currently no licensed vaccines. Due to the potential malicious use of B. pseudomallei as well as its impact on public health in regions where the disease is endemic, there is significant interest in developing vaccines for immunization against this disease. In the present study, type A O-polysaccharide (OPS) and manno-heptose capsular polysaccharide (CPS) antigens were isolated from nonpathogenic, select-agent-excluded strains of B. pseudomallei and covalently linked to carrier proteins. By using these conjugates (OPS2B1 and CPS2B1, respectively), it was shown that although high-titer IgG responses against the OPS or CPS component of the glycoconjugates could be raised in BALB/c mice, only those animals immunized with CPS2B1 were protected against intraperitoneal challenge with B. pseudomallei. Extending upon these studies, it was also demonstrated that when the mice were immunized with a combination of CPS2B1 and recombinant B. pseudomallei LolC, rather than with CPS2B1 or LolC individually, they exhibited higher survival rates when challenged with a lethal dose of B. pseudomallei. Collectively, these results suggest that CPS-based glycoconjugates are promising candidates for the development of subunit vaccines for immunization against melioidosis.
Insights
Developing a vaccine against melioidosis is crucial. Researchers found that a capsular polysaccharide (CPS) glycoconjugate, especially when combined with recombinant LolC, effectively protected mice against Burkholderia pseudomallei challenge.
Area of Science:
- Microbiology and Immunology
- Vaccine Development
- Bacterial Pathogenesis
Background:
- Melioidosis, caused by Burkholderia pseudomallei, is a severe and often fatal emerging infectious disease with no current vaccine.
- B. pseudomallei is a CDC tier 1 select agent with potential for malicious use, increasing the need for effective countermeasures.
- Current diagnosis and treatment of melioidosis are challenging, highlighting the urgency for preventative strategies.
Purpose of the Study:
- To evaluate the immunogenicity and protective efficacy of glycoconjugates derived from B. pseudomallei capsular polysaccharide (CPS) and O-polysaccharide (OPS) antigens.
- To determine if combining CPS-based vaccines with recombinant B. pseudomallei LolC enhances protection against melioidosis.
- To identify promising candidates for a subunit vaccine against B. pseudomallei infection.
Main Methods:
- Isolation and covalent linkage of type A O-polysaccharide (OPS) and manno-heptose capsular polysaccharide (CPS) antigens to carrier proteins, forming OPS2B1 and CPS2B1 conjugates.
- Immunization of BALB/c mice with OPS2B1 and CPS2B1 glycoconjugates to assess IgG responses.
- Challenge studies in mice using intraperitoneal injection of B. pseudomallei to evaluate protection conferred by CPS2B1, individually and in combination with recombinant B. pseudomallei LolC.
Main Results:
- Both OPS2B1 and CPS2B1 elicited high-titer IgG responses in mice.
- Only immunization with CPS2B1 provided protection against lethal B. pseudomallei challenge.
- A combination of CPS2B1 and recombinant B. pseudomallei LolC resulted in significantly higher survival rates compared to individual immunizations.
Conclusions:
- CPS-based glycoconjugates are promising candidates for developing subunit vaccines against melioidosis.
- Combining CPS-based vaccines with recombinant LolC may offer enhanced protective immunity against B. pseudomallei.
- Further research into CPS-based glycoconjugates holds potential for effective melioidosis immunization strategies.
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