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The development of a meningococcal disease vaccine based on Neisseria lactamica outer membrane vesicles
Andrew Gorringe1, Denise Halliwell, Mary Matheson
1Health Protection Agency, Porton Down, Salisbury SP4 0JG, UK. andrew.gorringe@hpa.org.uk
Abstract:
Serogroup B meningococcal disease remains a serious problem in many countries and no effective vaccine is currently available. Immunological and epidemiological evidence suggests that carriage of commensal Neisseria species is involved in the development of natural immunity against meningococcal disease. Neisseria lactamica has many surface structures in common with Neisseria meningitidis and may be the most important of these species. We have produced extensive pre-clinical data, which indicate that N. lactamica outer membrane vesicles (OMVs) may provide a vaccine effective against diverse disease-causing meningococcal strains. Immunisation with N. lactamica OMVs protected against lethal challenge with diverse meningococcal isolates in a mouse intraperitoneal challenge model of meningococcal disease and we are developing this vaccine for use in a phase I safety and immunogenicity study in adult volunteers. We have shown that OMVs produced from bacteria grown under iron-limited or iron-rich conditions provide equivalent protection in the mouse infection model and thus OMVs produced from iron-rich will be used. Sterile filtration of N. lactamica OMVs has proved difficult but this has been improved by resuspending the vesicles in a buffer, which increases their surface zeta potential. The vaccine is currently being manufactured and validated ELISA protocols have been developed for the analysis of serological responses.
Insights
Neisseria lactamica outer membrane vesicles (OMVs) show promise as a novel vaccine against Serogroup B meningococcal disease. Pre-clinical studies demonstrate protection against diverse strains, advancing to human trials.
Area of Science:
- Microbiology
- Vaccinology
- Immunology
Background:
- Serogroup B meningococcal disease poses a significant global health challenge with no currently available effective vaccine.
- Natural immunity against meningococcal disease is linked to carriage of commensal Neisseria species, particularly Neisseria lactamica.
- Neisseria lactamica shares surface structures with Neisseria meningitidis, suggesting its potential as a vaccine candidate.
Purpose of the Study:
- To evaluate the potential of Neisseria lactamica outer membrane vesicles (OMVs) as a vaccine against diverse meningococcal strains.
- To assess the efficacy of N. lactamica OMVs in a pre-clinical model of meningococcal disease.
- To prepare for a Phase I clinical trial investigating the safety and immunogenicity of the N. lactamica OMV vaccine.
Main Methods:
- Production of Neisseria lactamica outer membrane vesicles (OMVs).
- Evaluation of OMV efficacy in a mouse intraperitoneal challenge model against lethal doses of diverse meningococcal isolates.
- Optimization of OMV processing, including sterile filtration improvements via zeta potential modification.
- Development of validated ELISA protocols for serological response analysis.
Main Results:
- Immunization with N. lactamica OMVs conferred protection against lethal challenge with various meningococcal isolates in a mouse model.
- OMVs derived from bacteria grown under both iron-limited and iron-rich conditions demonstrated equivalent protective efficacy.
- Improved sterile filtration techniques for N. lactamica OMVs were developed by optimizing buffer conditions to enhance surface zeta potential.
Conclusions:
- Neisseria lactamica OMVs represent a promising vaccine candidate for protection against diverse Serogroup B meningococcal disease strains.
- The vaccine candidate is advancing towards a Phase I human safety and immunogenicity study.
- Manufacturing processes and analytical methods, including ELISA, are being validated for clinical progression.
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