Pathological response of a mouse model of lethal <italic style="font-style: italic">Vibrio vulnificus</italic> infection and its preliminary application in inactivated whole cell vaccine

ZHU Baohang; PAN Jiale; LIU Shulin; YE Yan; SONG Zhen; LI Yuxian; YANG Yun; SUN Hongwu; ZOU Quanming; PENG Liusheng

doi:10.16016/j.2097-0927.202412009

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Pathological response of a mouse model of lethal Vibrio vulnificus infection and its preliminary application in inactivated whole cell vaccine

Military Medicine | 更新时间：2025-04-14

- Pathological response of a mouse model of lethal Vibrio vulnificus infection and its preliminary application in inactivated whole cell vaccine
- Journal of Army Medical University Vol. 47, Issue 7, Pages: 656-663(2025)
- 作者机构：
  
  1.陆军军医大学（第三军医大学）药学与检验医学系微生物与生化药学教研室，重庆
  2.重庆理工大学药学院，重庆
- 作者简介：
  
  ZOU Quanming， E-mail： qmzou@tmmu.edu.cn
  PENG Liusheng， E-mail： pengliusheng06@163.com；
- 基金信息：
  
  Supported by the National Key Research and Development Program of China(2021YFC2302603)
- DOI：10.16016/j.2097-0927.202412009
  CLC： R-332;R378.3;R392.7
- Received：03 December 2024，
  
  Revised：30 December 2024，
  
  Published：15 April 2025
- 稿件说明：
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朱宝行,潘佳乐,刘姝琳,等.创伤弧菌致死性感染小鼠模型的组织病理改变及其在疫苗中的应用初探[J].陆军军医大学学报,2025,47(07):656-663.

Vibrio vulnificus infection and its preliminary application in inactivated whole cell vaccine[J].J Army Med Univ,2025,47(07):656-663.
朱宝行,潘佳乐,刘姝琳,等.创伤弧菌致死性感染小鼠模型的组织病理改变及其在疫苗中的应用初探[J].陆军军医大学学报,2025,47(07):656-663. DOI：10.16016/j.2097-0927.202412009.

Vibrio vulnificus infection and its preliminary application in inactivated whole cell vaccine[J].J Army Med Univ,2025,47(07):656-663. DOI：10.16016/j.2097-0927.202412009.ZHU Baohang,PAN Jiale,LIU Shulin,et al.Pathological response of a mouse model of lethal

摘要

目的

建立创伤弧菌最低致死剂量感染小鼠模型，评估创伤弧菌灭活全菌疫苗的免疫保护效果。

方法

采用不同剂量的创伤弧菌腹腔注射小鼠，确定感染的最低致死剂量；采用组织匀浆涂板检测脏器的细菌定植量，组织切片染色分析脏器的病理改变；将肝脏消化成单细胞悬液，采用流式细胞术检测免疫细胞的应答变化；制备创伤弧菌灭活全菌疫苗，采用不同途径免疫小鼠，观察疫苗的保护效果。

结果

成功确定了创伤弧菌腹腔感染的最低致死剂量为1×10

CFU，创伤弧菌感染后主要定植在小鼠的肝脏，并造成了肝脏的严重病理损伤；与未感染组小鼠相比，感染组小鼠肝脏中的中性粒细胞比例显著增加，而B细胞和T细胞的比例则相应的显著下降（

0.05）；小鼠经肌肉或腹腔单次注射灭活全菌疫苗7 d后即可有效抵抗创伤弧菌的致死性感染（

0.01），但血清IgG抗体的水平并未明显升高。

结论

成功确定了创伤弧菌最低致死剂量感染小鼠模型及其组织病理学应答特征，灭活全菌疫苗可能通过IgG抗体非依赖的方式介导对该创伤弧菌感染小鼠的快速免疫保护。

Abstract

‍Objective‍　‍To establish a mouse model of infection with the minimum lethal dose of

Vibrio vulnificus

(

V. vulnificus

) and to evaluate the protective efficacy of inactivated whole-cell (IWC) vaccine using this model. Methods‍　‍A mouse model of lethal-dose infection was established by intraperitoneal injection of different doses of

V. vulnificus

. Bacterial colonization in the organs was detected with tissue homogenate plating

and pathological changes in the organs were observed after tissue section

staining. Flow cytometry was used to detect immune cell responses after liver tissues were digested into single-cell suspension. IWC vaccine of

V. vulnificus

was prepared

and the mice were immunized through different routes to observe the protective efficacy of the vaccine. Results‍　‍A mouse model of infection with the minimum lethal dose at 1×10

CFU of

V. vulnificus

was successfully established. After infection

the bacteria were

mainly colonized in the liver of mice and caused severe pathological damages. Compared with the uninfected mice

the proportion of neutrophils in the liver was significantly increased in the infected mice

whereas the proportions of B cells and T cells were correspondingly decreased (

0.05). A single intramuscular or intraperitoneal injection of the IWC vaccine could protect the mice effectively against lethal infection of

V. vulnificus

in 7 d later (

0.01)

although the level of serum IgG having no significant increase. Conclusion‍　‍A mouse model of lethal-dose infection with

V. vulnificus

is successfully established

with histopathological characteristics. The IWC vaccine of

V. vulnificus

rapidly mediates immune protection in this model probably independent of IgG.

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Keywords

references

WANG J Y ， WENG X B ， WENG Y S ， et al . Clinical features and treatment outcomes of Vibrio vulnificus infection in the coastal city of Ningbo， China ［J］. Front Microbiol ， 2023 ， 14 ： 1220526 . DOI： 10.3389/fmicb.2023.1220526 http://dx.doi.org/10.3389/fmicb.2023.1220526 .

WORDEN P J ， BOGEMA D R ， MICALLEF M L ， et al . Phylogenomic diversity of Vibrio species and other Gammaproteobacteria isolated from Pacific oysters （ Crassostrea gigas ） during a summer mortality outbreak ［J］. Microb Genom ， 2022 ， 8 （ 12 ）： mgen000883 . DOI： 10.1099/mgen.0.000883 http://dx.doi.org/10.1099/mgen.0.000883 .

INTRIAGO P ， MONTIEL B ， VALAREZO M ， et al . Las bolitas syndrome in Penaeus vannamei hatcheries in Latin America ［J］. Microorganisms ， 2024 ， 12 （ 6 ）： 1186 . DOI： 10.3390/microorganisms12061186 http://dx.doi.org/10.3390/microorganisms12061186 .

MORGADO M E ， BRUMFIELD K D ， CHATTOPADHYAY S ， et al . Antibiotic resistance trends among Vibrio vulnificus and Vibrio parahaemolyticus isolated from the Chesapeake Bay， Maryland： a longitudinal study ［J］. Appl Environ Microbiol ， 2024 ， 90 （ 6 ）： e0053924 . DOI： 10.1128/aem.00539-24 http://dx.doi.org/10.1128/aem.00539-24 .

EFSA Panel on Biological Hazards BIOHAZ）， KOUTSOUMANIS K ， ALLENDE A ， et al . Public health aspects of Vibrio spp. related to the consumption of seafood in the EU ［J］. EFSA J ， 2024 ， 22 （ 7 ）： e8896 . DOI： 10.2903/j.efsa.2024.8896 http://dx.doi.org/10.2903/j.efsa.2024.8896 .

GANGWAR M ， USMANI M ， JAMAL Y ， et al . Environmental factors associated with incidence and distribution of V. parahaemolyticus and V. vulnificus in Chesapeake Bay， Maryland， USA： a three-year case study ［J］. bioRxiv ， 2023 ： 2023 .09. 25 . 559351 . DOI： 10.1101/2023.09.25.559351 http://dx.doi.org/10.1101/2023.09.25.559351 .

BARCIA-CRUZ R ， BALBOA S ， LEMA A ， et al . Comparative genomics of Vibrio toranzoniae strains ［J］. Int Microbiol ， 2024 . DOI： 10.1007/s10123-024-00557-z http://dx.doi.org/10.1007/s10123-024-00557-z .

ZHANG J X ， YUAN Y ， HU Q H ， et al . Identification of potential pathogenic targets and survival strategies of Vibrio vulnificus through population genomics ［J］. Front Cell Infect Microbiol ， 2023 ， 13 ： 1254379 . DOI： 10.3389/fcimb. 2023. 1254379 http://dx.doi.org/10.3389/fcimb.2023.1254379 .

HUANG X T ， LI X Y ， AN H R ， et al . Capsule type defines the capability of Klebsiella pneumoniae in evading Kupffer cell capture in the liver ［J］. PLoS Pathog ， 2022 ， 18 （ 8 ）： e1010693 . DOI： 10.1371/journal.ppat.1010693 http://dx.doi.org/10.1371/journal.ppat.1010693 .

AN H ， QIAN C ， HUANG Y ， et al . Functional vulnerability of liver macrophages to capsules defines virulence of blood-borne bacteria ［J］. J Exp Med ， 2022 ， 219 （ 4 ）： e20212032 . DOI： 10.1084/jem.20212032 http://dx.doi.org/10.1084/jem.20212032 .

HU T Y ， LIU C H ， LEI M ， et al . Metabolic regulation of the immune system in health and diseases： mechanisms and interventions ［J］. Signal Transduct Target Ther ， 2024 ， 9 （ 1 ）： 268 . DOI： 10.1038/s41392-024-01954-6 http://dx.doi.org/10.1038/s41392-024-01954-6 .

XU X M ， LIANG S Y ， LI X ， et al . Antibiotic resistance and virulence characteristics of Vibrio vulnificus isolated from Ningbo， China ［J］. Front Microbiol ， 2024 ， 15 ： 1459466 . DOI： 10.3389/fmicb.2024.1459466 http://dx.doi.org/10.3389/fmicb.2024.1459466 .

程浩，杨赟，孙红武，等 . TLR2/TLR9激动剂对鲍曼不动杆菌肺部感染的保护作用［J］. 陆军军医大学学报， 2024 ， 46 （ 8 ）： 829 - 836 . DOI： 10.16016/j.2097-0927.202401052 http://dx.doi.org/10.16016/j.2097-0927.202401052 .

CHENG H ， YANG Y ， SUN H W ， et al . Protective effect of TLR2/TLR9 agonists on pulmonary Acinetobacter baumannii infection in mice ［J］. J Army Med Univ ， 2024 ， 46 （ 8 ）： 829 - 836 . DOI： 10.16016/j.2097-0927.202401052 http://dx.doi.org/10.16016/j.2097-0927.202401052 .

WALTER K . What to know about Vibrio vulnificus ［J］. JAMA ， 2023 ， 329 （ 9 ）： 772 . DOI： 10.1001/jama.2023.0174 http://dx.doi.org/10.1001/jama.2023.0174 .

ARCHER E J ， BAKER-AUSTIN C ， OSBORN T J ， et al . Climate warming and increasing Vibrio vulnificus infections in North America ［J］. Sci Rep ， 2023 ， 13 （ 1 ）： 3893 . DOI： 10.1038/s41598-023-28247-2 http://dx.doi.org/10.1038/s41598-023-28247-2 .

LYDON K A ， KINSEY T ， LE C ， et al . Biochemical and virulence characterization of Vibrio vulnificus isolates from clinical and environmental sources ［J］. Front Cell Infect Microbiol ， 2021 ， 11 ： 637019 . DOI： 10.3389/fcimb. 2021. 637019 http://dx.doi.org/10.3389/fcimb.2021.637019 .

JAYAKUMAR J M ， MARTINEZ-URTAZA J ， BRUMFIELD K D ， et al . Climate change and Vibrio vulnificus dynamics： a blueprint for infectious diseases ［J］. PLoS Pathog ， 2024 ， 20 （ 12 ）： e1012767 . DOI： 10.1371/journal.ppat.1012767 http://dx.doi.org/10.1371/journal.ppat.1012767 .

KIM H Y ， DAVOODBASHA M ， KIM J W . Functional characterization of maltodextrin glucosidase for maltodextrin and glycogen metabolism in Vibrio vulnificus MO6-24/O ［J］. Arch Microbiol ， 2022 ， 204 （ 11 ）： 668 . DOI： 10.1007/s00203-022-03274-1 http://dx.doi.org/10.1007/s00203-022-03274-1 .

WANG J J ， AN H R ， DING M ， et al . Liver macrophages and sinusoidal endothelial cells execute vaccine-elicited capture of invasive bacteria ［J］. Sci Transl Med ， 2023 ， 15 （ 727 ）： eade0054 . DOI： 10.1126/scitranslmed.ade0054 http://dx.doi.org/10.1126/scitranslmed.ade0054 .

LIN W P ， MU X ， CHEN S H ， et al . Clinical characteristics of 11 patients with Vibrio vulnificus infection and the establishment of a rapid diagnosis procedure for this disease ［J］. Chin J Burns Wounds ， 2024 ， 40 （ 3 ）： 266 - 272 . DOI： 10.3760/cma.j.cn501225-20230803-00036 http://dx.doi.org/10.3760/cma.j.cn501225-20230803-00036 .

IBÁNYEZ-PAYÁ P ， BLASCO A ， ROS-LIS J V ， et al . Electrolyzed water treatment for the control of the zoonotic pathogen Vibrio vulnificus in aquaculture： a one health perspective ［J］. Microorganisms ， 2024 ， 12 （ 10 ）： 1992 . DOI： 10.3390/microorganisms12101992 http://dx.doi.org/10.3390/microorganisms12101992 .

RAFEI R ， OSMAN M ， KASSEM I I ， et al . Spotlight on the epidemiology and antimicrobial susceptibility profiles of Vibrio species in the MENA region， 2000-2023 ［J］. Future Microbiol ， 2024 ， 19 （ 15 ）： 1333 - 1353 . DOI： 10.1080/17460913.2024.2392460 http://dx.doi.org/10.1080/17460913.2024.2392460 .

GU Q Q ， WANG G H ， LI N Q ， et al . Evaluation of the efficacy of a novel Vibrio vulnificus vaccine based on antibacterial peptide inactivation in turbot， Scophthalmus maximus ［J］. Fish Shellfish Immunol ， 2021 ， 118 ： 197 - 204 . DOI： 10.1016/j.fsi.2021.09.008 http://dx.doi.org/10.1016/j.fsi.2021.09.008 .

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⁰

Pathological response of a mouse model of lethal Vibrio vulnificus infection and its preliminary application in inactivated whole cell vaccine

DOI：10.16016/j.2097-0927.202412009

摘要

Abstract

关键词

Keywords

references