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Activation and Conjugation of Soluble Polysaccharides using 1-Cyano-4-Dimethylaminopyridine Tetrafluoroborate CDAP
Published on: June 14, 2021
Production and efficacy of a low-cost recombinant pneumococcal protein polysaccharide conjugate vaccine
Jenny A Herbert1, Emily J Kay2, Sian E Faustini3
1Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, England, UK.
Insights
This study introduces novel recombinant vaccines against Streptococcus pneumoniae, produced affordably in E. coli. These vaccines show promise in preventing pneumococcal pneumonia, offering a potential low-cost alternative for global health.
Area of Science:
- Vaccinology
- Microbiology
- Biotechnology
Background:
- Streptococcus pneumoniae is a major cause of bacterial pneumonia, responsible for over a million deaths annually, particularly in children under five.
- High vaccine costs limit availability in developing nations, contributing to the significant disease burden.
- Current protein polysaccharide conjugate vaccines, like Prevnar13, are effective but involve expensive, multi-step production processes.
Purpose of the Study:
- To design, purify, and produce novel recombinant pneumococcal protein polysaccharide conjugate vaccines using Escherichia coli as a production platform.
- To evaluate the efficacy of these novel recombinant vaccines in a murine model of pneumococcal pneumonia.
- To compare the protective ability of the recombinant vaccines against invasive disease with the efficacy of Prevnar13.
Main Methods:
- Development of recombinant vaccines using Escherichia coli as a host for low-cost production.
- Purification of the novel recombinant protein polysaccharide conjugate vaccines.
- Efficacy testing in a murine model of Streptococcus pneumoniae pneumonia, comparing outcomes to Prevnar13.
Main Results:
- Successful design, purification, and production of novel recombinant pneumococcal protein polysaccharide conjugate vaccines in E. coli.
- Demonstration of vaccine efficacy in a murine model, indicating protection against pneumococcal pneumonia.
- Proof of principle established for E. coli-produced conjugate vaccines preventing pneumococcal infection.
Conclusions:
- Recombinant protein polysaccharide conjugate vaccines produced in E. coli offer a viable, low-cost alternative to current vaccine production methods.
- This approach has the potential to increase vaccine accessibility, particularly in resource-limited settings.
- Further development could lead to more affordable and widely available vaccines against Streptococcus pneumoniae.
Abstract:
Streptococcus pneumoniae is the leading cause of bacterial pneumonia. Although this is a vaccine preventable disease, S. pneumoniae still causes over 1 million deaths per year, mainly in children under the age of five. The biggest disease burden is in the developing world, which is mainly due to unavailability of vaccines due to their high costs. Protein polysaccharide conjugate vaccines are given routinely in the developed world to children to induce a protective antibody response against S. pneumoniae. One of these vaccines is Prevnar13, which targets 13 of the 95 known capsular types. Current vaccine production requires growth of large amounts of the 13 serotypes, and isolation of the capsular polysaccharide that is then chemically coupled to a protein, such as the diphtheria toxoid CRM197, in a multistep expensive procedure. In this study, we design, purify and produce novel recombinant pneumococcal protein polysaccharide conjugate vaccines in Escherichia coli, which act as mini factories for the low-cost production of conjugate vaccines. Recombinant vaccine efficacy was tested in a murine model of pneumococcal pneumonia; ability to protect against invasive disease was compared to that of Prevnar13. This study provides the first proof of principle that protein polysaccharide conjugate vaccines produced in E. coli can be used to prevent pneumococcal infection. Vaccines produced in this manner may provide a low-cost alternative to the current vaccine production methodology.
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