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Published on: May 2, 2018
Protection against experimental melioidosis following immunisation with a lipopolysaccharide-protein conjugate
Andrew E Scott1, Sarah A Ngugi1, Thomas R Laws1
1Defence Science and Technology Laboratory, Porton Down, Salisbury SP4 0JQ, UK.
Abstract:
Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei. It is refractory to antibiotic treatment and there is currently no licensed vaccine. In this report we detail the construction and protective efficacy of a polysaccharide-protein conjugate composed of B. pseudomallei lipopolysaccharide and the Hc fragment of tetanus toxin. Immunisation of mice with the lipopolysaccharide-conjugate led to significantly reduced bacterial burdens in the spleen 48 hours after challenge and afforded significant protection against a lethal challenge with B. pseudomallei. The conjugate generated significantly higher levels of antigen-specific IgG1 and IgG2a than in lipopolysaccharide-immunised mice. Immunisation with the conjugate also demonstrated a bias towards Th1 type responses, evidenced by high levels of IgG2a. In contrast, immunisation with unconjugated lipopolysaccharide evoked almost no IgG2a demonstrating a bias towards Th2 type responses. This study demonstrates the effectiveness of this approach in the development of an efficacious and protective vaccine against melioidosis.
Insights
A new vaccine using a Burkholderia pseudomallei lipopolysaccharide-tetanus toxin conjugate protects mice against melioidosis. This conjugate vaccine shows promise for preventing this severe infectious disease.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei.
- The disease is difficult to treat with antibiotics and lacks a licensed vaccine.
- Burkholderia pseudomallei poses a significant global health challenge.
Purpose of the Study:
- To develop and evaluate a novel conjugate vaccine against melioidosis.
- To assess the protective efficacy of a B. pseudomallei lipopolysaccharide-tetanus toxin conjugate in a mouse model.
- To investigate the immune response elicited by the conjugate vaccine.
Main Methods:
- Construction of a polysaccharide-protein conjugate using B. pseudomallei lipopolysaccharide and tetanus toxin Hc fragment.
- Immunization of mice with the conjugate vaccine.
- Assessment of bacterial burden in spleen post-challenge with B. pseudomallei.
- Analysis of antigen-specific IgG1 and IgG2a antibody levels and T-helper cell responses.
Main Results:
- Mice immunized with the conjugate showed significantly reduced bacterial loads in the spleen.
- The conjugate vaccine provided significant protection against lethal B. pseudomallei challenge.
- Conjugate immunization induced higher levels of antigen-specific IgG1 and IgG2a compared to unconjugated lipopolysaccharide.
- The conjugate vaccine promoted a Th1-biased immune response, indicated by high IgG2a levels.
Conclusions:
- The developed lipopolysaccharide-conjugate vaccine is effective in protecting against melioidosis in mice.
- This conjugate vaccine strategy holds promise for the development of a viable vaccine against melioidosis.
- The study highlights the potential of conjugate vaccines in eliciting protective immunity against challenging bacterial infections.
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