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Pneumonic Plague Protection Induced by a Monophosphoryl Lipid A Decorated Yersinia Outer‐Membrane‐Vesicle Vaccine

Majumder, Saugata ; Das, Shreya ; Li, Peng ; Yang, Nicole ; Dellario, Hazel ; Sui, Haixin ; Guan, Ziqiang ; Sun, Wei

Small (Weinheim an der Bergstrasse, Germany), 2024-04, Vol.20 (15), p.e2307066-n/a [Periódico revisado por pares]

Germany: Wiley Subscription Services, Inc

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  • Título:
    Pneumonic Plague Protection Induced by a Monophosphoryl Lipid A Decorated Yersinia Outer‐Membrane‐Vesicle Vaccine
  • Autor: Majumder, Saugata ; Das, Shreya ; Li, Peng ; Yang, Nicole ; Dellario, Hazel ; Sui, Haixin ; Guan, Ziqiang ; Sun, Wei
  • Assuntos: Animals ; Antigens, Bacterial ; Feasibility studies ; Immunization ; Lipid A - analogs & derivatives ; Lipids ; Lungs ; Membranes ; Mice ; monophosphoryl lipid A ; OUTER membrane vesicles ; Plague - prevention & control ; Plague Vaccine ; protective immunity ; Vaccines ; Y. pestis ; Yersinia ; Yersinia pestis
  • É parte de: Small (Weinheim an der Bergstrasse, Germany), 2024-04, Vol.20 (15), p.e2307066-n/a
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
  • Descrição: 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. A new Yersinia pseudotuberculosis mutant strain, YptbS46, encompassing lpxE insertion and pmrF‐J deletion, exclusively produce monophosphoryl lipid A (MPLA) having adjuvant properties. OMVs from YptbS46 contain MPLA, high amounts of LcrV and display low TLR4 activation, resulting in substantially reduced reactogenicity, complete protection to mice against pneumonic plague. The study strongly demonstrates OMV46‐LcrV as a new improved plague vaccine candidate.
  • Editor: Germany: Wiley Subscription Services, Inc
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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