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Published on: July 25, 2022
Pneumonic Plague Protection Induced by a Monophosphoryl Lipid A Decorated Yersinia Outer-Membrane-Vesicle Vaccine
Saugata Majumder1, Shreya Das1, Peng Li1
1Department of Immunology and Microbial Disease, Albany Medical College, Albany, NY, 12208, USA.
Abstract:
A new Yersinia pseudotuberculosis mutant strain, YptbS46, carrying the lpxE insertion and pmrF-J deletion is constructed and shown to exclusively produce monophosphoryl lipid A (MPLA) having adjuvant properties. Outer membrane vesicles (OMVs) isolated from YptbS46 harboring an lcrV expression plasmid, pSMV13, are designated OMV46-LcrV, which contained MPLA and high amounts of LcrV (Low Calcium response V) and displayed low activation of Toll-like receptor 4 (TLR4). Intramuscular prime-boost immunization with 30 µg of of OMV46-LcrV exhibited substantially reduced reactogenicity than the parent OMV44-LcrV and conferred complete protection to mice against a high-dose of respiratory Y. pestis challenge. OMV46-LcrV immunization induced robust adaptive responses in both lung mucosal and systemic compartments and orchestrated innate immunity in the lung, which are correlated with rapid bacterial clearance and unremarkable lung damage during Y. pestis challenge. Additionally, OMV46-LcrV immunization conferred long-term protection. Moreover, immunization with reduced doses of OMV46-LcrV exhibited further lower reactogenicity and still provided great protection against pneumonic plague. The studies strongly demonstrate the feasibility of OMV46-LcrV as a new type of plague vaccine candidate.
Insights
A novel plague vaccine candidate, OMV46-LcrV, derived from Yersinia pseudotuberculosis, offers complete protection against Y. pestis challenge with reduced side effects. This monophosphoryl lipid A (MPLA)-containing vaccine shows significant promise for preventing pneumonic plague.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Yersinia pestis causes plague, a severe infectious disease.
- Current vaccines have limitations in efficacy and safety.
- Outer membrane vesicles (OMVs) are promising vaccine platforms.
Purpose of the Study:
- To develop a novel Yersinia pestis vaccine candidate.
- To evaluate the immunogenicity and protective efficacy of OMV46-LcrV.
- To assess the reactogenicity and long-term protection of the candidate vaccine.
Main Methods:
- Construction of a Yersinia pseudotuberculosis mutant strain (YptbS46) producing monophosphoryl lipid A (MPLA).
- Isolation of OMVs (OMV46-LcrV) containing MPLA and LcrV from the mutant strain.
- Immunization of mice with OMV46-LcrV and challenge with Y. pestis.
Main Results:
- OMV46-LcrV demonstrated significantly reduced reactogenicity compared to parent OMVs.
- Complete protection against high-dose Y. pestis challenge was achieved.
- Robust adaptive and innate immune responses were induced in both systemic and mucosal compartments.
- Long-term protection and protection with reduced doses were observed.
Conclusions:
- OMV46-LcrV is a promising candidate for a new plague vaccine.
- The vaccine elicits protective immunity with favorable safety profile.
- Further development of OMV46-LcrV for plague prevention is warranted.
