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Evaluation of lipopolysaccharide and capsular polysaccharide as subunit vaccines against experimental melioidosis
Michelle Nelson1, Joann L Prior1, M Stephen Lever1
1Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.
Abstract:
Burkholderia pseudomallei is the causative agent of melioidosis, which is a major cause of morbidity and mortality in endemic regions. Currently there is no human vaccine against melioidosis. In this study, LPS or capsular polysaccharide was used to immunize BALB/c mice. The different polysaccharide antigens induced antibody responses. Mice vaccinated with LPS developed predominantly IgM and IgG3 responses. Contrastingly, mice vaccinated with capsular polysaccharide developed a predominantly IgG2b response. After immunization, mice were challenged by the intra-peritoneal route and an increased mean time to death was observed compared with unvaccinated controls. Immunization with LPS provided an optimal protective response. Mice challenged by the aerosol route showed a small increase in the mean time to death compared with the unvaccinated controls. The passive transfer of antigen from immunized into naive mice provided protection against a subsequent challenge. This study is the first time antigens protective by active immunization have been identified and suggests that polysaccharides have potential as vaccine candidates against melioidosis.
Insights
This study identified protective antigens for a potential melioidosis vaccine. Immunizing mice with lipopolysaccharide (LPS) or capsular polysaccharide showed promising results against Burkholderia pseudomallei.
Area of Science:
- * Infectious diseases
- * Immunology
- * Vaccinology
Background:
- * Melioidosis, caused by Burkholderia pseudomallei, is a significant global health concern with no existing human vaccine.
- * Current treatment relies on prolonged antibiotic courses, highlighting the urgent need for preventative strategies like vaccination.
Purpose of the Study:
- * To investigate the immunogenicity and protective efficacy of lipopolysaccharide (LPS) and capsular polysaccharide from Burkholderia pseudomallei in a murine model.
- * To identify potential vaccine candidates for melioidosis prevention.
Main Methods:
- * BALB/c mice were immunized with either LPS or capsular polysaccharide.
- * Antibody responses (IgM, IgG subclasses) were analyzed post-immunization.
- * Mice were challenged via intraperitoneal and aerosol routes to assess survival and mean time to death.
- * Passive transfer of antibodies from immunized to naive mice was performed to evaluate protective immunity.
Main Results:
- * Both LPS and capsular polysaccharide elicited distinct antibody responses, with LPS inducing primarily IgM and IgG3, and capsular polysaccharide inducing IgG2b.
- * Immunization with LPS demonstrated an optimal protective effect, significantly increasing mean time to death in challenged mice.
- * Passive antibody transfer conferred protection against subsequent challenge, confirming the role of antibodies in immunity.
Conclusions:
- * Polysaccharide antigens, particularly LPS, show significant potential as vaccine candidates against melioidosis.
- * This research identifies key antigens for developing active immunization strategies against this neglected tropical disease.
