Immunogenicity and protective efficacy of the recombinant Pasteurella multocida lipoproteins VacJ and PlpE, and outer membrane protein H from P. multocida A:1 in ducks

Li, Yajuan; Xiao, Junfang; Chang, Yung-Fu; Zhang, Hui; Teng, Yutao; Lin, Wencheng; Li, Hongxin; Chen, Weiguo; Zhang, Xinheng; Xie, Qingmei

doi:10.3389/fimmu.2022.985993

Cited by 7 publications

(8 citation statements)

References 45 publications

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“…Furthermore, lipoprotein E (A5H9S0) has also been identified. Lipoprotein E plays a critical role as an immunogenic membrane protein with variable serotype coverage, immunogenicity, antigenicity, and accessible antibodies and is responsible for facilitating complement-mediated killing (Li et al 2022 ). Our findings show that P .…”

Section: Discussionmentioning

confidence: 99%

Characterization and immunological effect of outer membrane vesicles from Pasteurella multocida on macrophages

Sun,

Huang,

et al. 2024

Appl Microbiol Biotechnol

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Pasteurella multocida is an important bacterial pathogen that can cause diseases in both animals and humans. Its elevated morbidity and mortality rates in animals result in substantial economic repercussions within the livestock industry. The prevention of diseases caused by P. multocida through immunization is impeded by the absence of a safe and effective vaccine. Outer membrane vesicles (OMVs) secreted from the outer membrane of Gram-negative bacteria are spherical vesicular structures that encompass an array of periplasmic components in conjunction with a diverse assortment of lipids and proteins. These vesicles can induce antibacterial immune responses within the host. P. multocida has been shown to produce OMVs. Nonetheless, the precise characteristics and immunomodulatory functions of P. multocida OMVs have not been fully elucidated. In this study, OMVs were isolated from P. multocida using an ultrafiltration concentration technique, and their morphology, protein constitution, and immunomodulatory properties in RAW264.7 cells were studied. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) revealed that the OMVs exhibited typical spherical and bilayered lipid vesicular architecture, exhibiting an average diameter of approximately 147.5 nm. The yield of OMVs was 2.6 × 1011 particles/mL. Proteomic analysis revealed a high abundance of membrane-associated proteins within P. multocida OMVs, with the capability to instigate the host’s immune response. Furthermore, OMVs stimulated the proliferation and cellular uptake of macrophages and triggered the secretion of cytokines, such as TNF-ɑ, IL-1β, IL-6, IL-10, and TGF-β1. Consequently, our results indicated that OMVs from P. multocida could directly interact with macrophages and regulate their immune function in vitro. These results supported the prospective applicability of P. multocida OMVs as a platform in the context of vaccine development. Key points • Preparation and characterization of P. multocida OMVs. • P. multocida OMVs possess a range of antigens and lipoproteins associated with the activation of the immune system. • P. multocida OMVs can activate the proliferation, internalization, and cytokine secretion of macrophages in vitro.

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Section: Discussionmentioning

confidence: 99%

Characterization and immunological effect of outer membrane vesicles from Pasteurella multocida on macrophages

Sun,

Huang,

et al. 2024

Appl Microbiol Biotechnol

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“…P. multocida causes different infectious diseases in animals and humans, and in particular, it causes severe respiratory diseases in bovines that are associated with high mortality rates. Antibiotics are mainly used to treat P. multocida infection, but the overuse of antibiotics results in the development of bacterial resistance [ 27 ]. In addition, there are no effective vaccines to efficiently prevent P. multocida infection, so new strategies are needed to treat or prevent P. multocida infection.…”

Section: Discussionmentioning

confidence: 99%

RACK1 mediates NLRP3 inflammasome activation during Pasteurella multocida infection

Ran,

Yin,

et al. 2023

Vet Res

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Pasteurella multocida is a gram-negative bacterium that causes serious diseases in a wide range of animal species. Inflammasomes are intracellular multimolecular protein complexes that play a critical role in host defence against microbial infection. Our previous study showed that bovine P. multocida type A (PmCQ2) infection induces NLRP3 inflammasome activation. However, the exact mechanism underlying PmCQ2-induced NLRP3 inflammasome activation is not clear. Here, we show that NLRP3 inflammasome activation is positively regulated by a scaffold protein called receptor for activated C kinase 1 (RACK1). This study shows that RACK1 expression was downregulated by PmCQ2 infection in primary mouse peritoneal macrophages and mouse tissues, and overexpression of RACK1 prevented PmCQ2-induced cell death and reduced the numbers of adherent and invasive PmCQ2, indicating a modulatory role of RACK1 in the cell death that is induced by P. multocida infection. Next, RACK1 knockdown by siRNA significantly attenuated PmCQ2-induced NLRP3 inflammasome activation, which was accompanied by a reduction in the protein expression of interleukin (IL)-1β, pro-IL-1β, caspase-1 and NLRP3 as well as the formation of ASC specks, while RACK1 overexpression by pcDNA3.1-RACK1 plasmid transfection significantly promoted PmCQ2-induced NLRP3 inflammasome activation; these results showed that RACK1 is essential for NLRP3 inflammasome activation. Furthermore, RACK1 knockdown decreased PmCQ2-induced NF-κB activation, but RACK1 overexpression had the opposite effect. In addition, the immunofluorescence staining and immunoprecipitation results showed that RACK1 colocalized with NLRP3 and that NEK7 and interacted with these proteins. However, inhibition of potassium efflux significantly attenuated the RACK1-NLRP3-NEK7 interaction. Our study demonstrated that RACK1 plays an important role in promoting NLRP3 inflammasome activation by regulating NF-κB and promoting NLRP3 inflammasome assembly.

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“…The Group 4 (n = 45) of mice were inoculated subcutaneously with 0.2 mL of P . multocida vaccine as a control vaccine [ 60 ]. Finally, Group 5 serves as a blank control (without any interventions, mainly for pathological histological analysis).…”

Section: Methodsmentioning

confidence: 99%

Recombinant-attenuated Salmonella enterica serovar Choleraesuis vector expressing the PlpE protein of Pasteurella multocida protects mice from lethal challenge

Zhou,

Tian,

Tian

et al. 2023

BMC Vet Res

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Background Bacterial surface proteins play key roles in pathogenicity and often contribute to microbial adhesion and invasion. Pasteurella lipoprotein E (PlpE), a Pasteurella multocida (P. multocida) surface protein, has recently been identified as a potential vaccine candidate. Live attenuated Salmonella strains have a number of potential advantages as vaccine vectors, including immunization with live vector can mimic natural infections by organisms, lead to the induction of mucosal, humoral, and cellular immune responses. In this study, a previously constructed recombinant attenuated Salmonella Choleraesuis (S. Choleraesuis) vector rSC0016 was used to synthesize and secrete the surface protein PlpE of P. multocida to form the vaccine candidate rSC0016(pS-PlpE). Subsequently, the immunogenicity of S. Choleraesuis rSC0016(pS-PlpE) as an oral vaccine to induce protective immunity against P. multocida in mice was evaluated. Results After immunization, the recombinant attenuated S. Choleraesuis vector can efficiently delivered P. multocida PlpE protein in vivo and induced a specific immune response against this heterologous antigen in mice. In addition, compared with the inactivated vaccine, empty vector (rSC0016(pYA3493)) and PBS immunized groups, the rSC0016(pS-PlpE) vaccine candidate group induced higher antigen-specific mucosal, humoral and mixed Th1/Th2 cellular immune responses. After intraperitoneal challenge, the rSC0016(pS-PlpE) immunized group had a markedly enhanced survival rate (80%), a better protection efficiency than 60% of the inactivated vaccine group, and significantly reduced tissue damage. Conclusions In conclusion, our study found that the rSC0016(pS-PlpE) vaccine candidate provided good protection against challenge with wild-type P. multocida serotype A in a mouse infection model, and may potentially be considered for use as a universal vaccine against multiple serotypes of P. multocida in livestock, including pigs.

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Immunogenicity and protective efficacy of the recombinant Pasteurella multocida lipoproteins VacJ and PlpE, and outer membrane protein H from P. multocida A:1 in ducks

Cited by 7 publications

References 45 publications

Characterization and immunological effect of outer membrane vesicles from Pasteurella multocida on macrophages

Characterization and immunological effect of outer membrane vesicles from Pasteurella multocida on macrophages

RACK1 mediates NLRP3 inflammasome activation during Pasteurella multocida infection

Recombinant-attenuated Salmonella enterica serovar Choleraesuis vector expressing the PlpE protein of Pasteurella multocida protects mice from lethal challenge

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