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Updated: Jul 5, 2025
A Precise Pathogen Delivery and Recovery System for Murine Models of Secondary Bacterial Pneumonia
Published on: September 21, 2019
A bacterial vesicle-based pneumococcal vaccine against influenza-mediated secondary Streptococcus pneumoniae
Saugata Majumder1, Peng Li1, Shreya Das1
1Department of Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA.
Abstract:
Streptococcus pneumoniae (Spn) is a common pathogen causing a secondary bacterial infection following influenza, which leads to severe morbidity and mortality during seasonal and pandemic influenza. Therefore, there is an urgent need to develop bacterial vaccines that prevent severe post-influenza bacterial pneumonia. Here, an improved Yersinia pseudotuberculosis strain (designated as YptbS46) possessing an Asd+ plasmid pSMV92 could synthesize high amounts of the Spn pneumococcal surface protein A (PspA) antigen and monophosphoryl lipid A as an adjuvant. The recombinant strain produced outer membrane vesicles (OMVs) enclosing a high amount of PspA protein (designated as OMV-PspA). A prime-boost intramuscular immunization with OMV-PspA induced both memory adaptive and innate immune responses in vaccinated mice, reduced the viral and bacterial burden, and provided complete protection against influenza-mediated secondary Spn infection. Also, the OMV-PspA immunization afforded significant cross-protection against the secondary Spn A66.1 infection and long-term protection against the secondary Spn D39 challenge. Our study implies that an OMV vaccine delivering Spn antigens can be a new promising pneumococcal vaccine candidate.
Insights
Developing a novel outer membrane vesicle (OMV) vaccine using a modified Yersinia pseudotuberculosis strain, researchers created OMV-PspA. This vaccine effectively protects against secondary Streptococcus pneumoniae infections following influenza.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Influenza infections often lead to severe secondary bacterial pneumonia caused by Streptococcus pneumoniae (Spn).
- Existing vaccines lack comprehensive protection against post-influenza Spn infections, highlighting the need for new vaccine strategies.
Purpose of the Study:
- To develop and evaluate a novel outer membrane vesicle (OMV) vaccine candidate for preventing severe Spn pneumonia after influenza.
- To assess the immunogenicity and protective efficacy of the OMV-PspA vaccine in a mouse model.
Main Methods:
- Engineered a Yersinia pseudotuberculosis strain (YptbS46) with a plasmid (pSMV92) to produce high levels of Spn pneumococcal surface protein A (PspA) and monophosphoryl lipid A.
- Generated PspA-containing OMVs (OMV-PspA) from the engineered strain.
- Administered prime-boost intramuscular immunization with OMV-PspA to mice and challenged them with influenza and Spn.
Main Results:
- OMV-PspA immunization induced robust adaptive and innate immune memory responses.
- Vaccinated mice showed reduced viral and bacterial loads and complete protection against lethal secondary Spn infection post-influenza.
- The OMV-PspA vaccine demonstrated cross-protection against different Spn strains (A66.1, D39) and provided long-term immunity.
Conclusions:
- OMV-PspA is a promising vaccine candidate for preventing severe secondary Spn infections following influenza.
- OMV-based vaccines displaying Spn antigens represent a novel approach for pneumococcal vaccine development.
