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Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Immunization with a ZmpB-based protein vaccine could protect against pneumococcal diseases in mice
Yi Gong1, Wenchun Xu, Yali Cui
1Department of Laboratory Medicine, Chongqing Medical University, Chongqing, People's Republic of China.
Abstract:
Zinc metalloprotease B (ZmpB) is present in all isolated pneumococcal strains and contributes to the pathogenesis of pneumococcal infection. In this study, recombinant ZmpB was cloned and expressed in Escherichia coli. The expression of ZmpB by different pneumococcal strains was detectable by Western blotting with antisera raised to recombinant ZmpB. Flow cytometry analysis demonstrated that anti-ZmpB polyclonal antibodies could bind to the cell surface of the pneumococcal strains analyzed. Both recombinant ZmpB protein and anti-ZmpB polyclonal antibodies significantly inhibited the adhesion of Streptococcus pneumoniae D39 to A549 cells. In mouse models, mucosal immunization with recombinant ZmpB could significantly reduce pneumococcal lung colonization caused by S. pneumoniae serotypes 19F and 14 and significantly increase mice survival times following invasive pneumococcal challenge with different pneumococcal strains, including serotypes 2, 3, 6B, and 14. Furthermore, intraperitoneal immunization with recombinant ZmpB in combination with the recombinant pneumolysin mutant (DeltaA146 Ply) and heat shock protein 40 (DnaJ) could enhance the protection against pneumococcal infection compared to protection provided by single-protein antigens. Passive immunization with hyperimmune antisera against these three antigens also demonstrated that the combination of three hyperimmune antisera could provide better protection than single antisera. Taken together, our results suggest that ZmpB is a good candidate pneumococcal vaccine antigen.
Insights
Zinc metalloprotease B (ZmpB) is a key factor in pneumococcal infections. This study shows ZmpB is a promising vaccine candidate, significantly reducing bacterial colonization and improving survival rates in mice.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Zinc metalloprotease B (ZmpB) is a virulence factor found in all Streptococcus pneumoniae strains.
- Understanding ZmpB's role in pathogenesis is crucial for developing new pneumococcal vaccines.
Purpose of the Study:
- To investigate the potential of ZmpB as a vaccine antigen against pneumococcal infections.
- To evaluate the efficacy of ZmpB in preventing Streptococcus pneumoniae colonization and invasive disease.
Main Methods:
- Recombinant ZmpB was expressed and characterized.
- Antibodies against ZmpB were generated and tested for binding and inhibitory effects.
- Efficacy of ZmpB immunization was assessed in mouse models of pneumococcal lung colonization and invasive infection.
Main Results:
- Anti-ZmpB antibodies bound to the pneumococcal cell surface and inhibited bacterial adhesion to host cells.
- Mucosal immunization with ZmpB reduced lung colonization by S. pneumoniae serotypes 19F and 14.
- ZmpB immunization increased survival rates in mice challenged with various pneumococcal serotypes.
- Combination immunization with ZmpB, DeltaA146 Ply, and DnaJ provided enhanced protection.
Conclusions:
- ZmpB is a significant virulence factor and a viable candidate for pneumococcal vaccine development.
- ZmpB-based vaccines hold promise for protecting against diverse S. pneumoniae strains and invasive disease.

