Heterologous Prime-Boost Immunization with DNA Vaccine and Modified Recombinant Proteins Enhances Immune Response against Trueperella pyogenes in Mice

Trueperella pyogenes (T. pyogenes) is a crucial opportunistic pathogen normally causing mastitis, abscesses and pneumonia in economically important ruminants. Although only one commercial vaccine of T. pyogenes is currently obtainable, its immunoprotective effect is limited. Pyolysin (PLO) is the most predominant virulence factor highly expressed in T. pyogenes and is an excellent target for the development of novel vaccines against T. pyogenes. In this study, we designed a heterologous prime-boost vaccination scheme combining a DNA vaccine pVAX1-PLO and a subunit vaccine His-PLO to maximize host responses in mice. Humoral and cellular immune responses and protective effects were evaluated in mice to compare the immunogenicity induced by different immunization schemes. Compared to the PBS-control group, in vivo immunization results showed that better immune responses of mice immunized with the pVAX1-PLO plasmids and His-PLO proteins were induced. The residual bacterial burdens from the liver and peritoneal fluid were remarkably decreased in the immunized mice compared with the PBS group. Notably, the heterologous prime-boost vaccination groups significantly enhanced host humoral and cellular immune responses and protected mice from different virulent T. pyogenes strains infection. Conclusively, this study provides a favorable strategy for the further development of next-generation vaccines against T. pyogenes infections.

[1]  W. Han,et al.  vB-ApyS-JF1, the First Trueperella pyogenes Phage, Shows Potential as an Alternative Treatment Strategy for Trueperella pyogenes Infections , 2021, Frontiers in Microbiology.

[2]  T. G. Sumithra,et al.  A novel bicistronic DNA vaccine with the enhanced protective immune response against Bacillus anthracis through DNA prime-protein boost vaccination approach. , 2021, Microbial pathogenesis.

[3]  Sedef Erkunt Alak,et al.  GRA8 DNA vaccine formulations protects against chronic toxoplasmosis. , 2021, Microbial pathogenesis.

[4]  Zachary Meili.  Trueperella pyogenes pharyngitis in an immunocompetent 40-year-old man , 2020, BMJ Case Reports.

[5]  Min Wu,et al.  MicroRNA-302/367 Cluster Impacts Host Antimicrobial Defense via Regulation of Mitophagic Response Against Pseudomonas aeruginosa Infection , 2020, Frontiers in Immunology.

[6]  S. Boscardin,et al.  Homologous prime-boost with Zika virus envelope protein and poly (I:C) induces robust specific humoral and cellular immune responses. , 2020, Vaccine.

[7]  M. Zheng,et al.  Immunization with DNA prime-subunit protein boost strategy based on influenza H9N2 virus conserved matrix protein M1 and its epitope screening , 2020, Scientific Reports.

[8]  E. Malchiodi,et al.  Mucosal Heterologous Prime/Boost Vaccination Induces Polyfunctional Systemic Immunity, Improving Protection Against Trypanosoma cruzi , 2020, Frontiers in Immunology.

[9]  Bo Ma,et al.  Evaluation of the Potency of Two Pyolysin-Derived Recombinant Proteins as Vaccine Candidates of Trueperella Pyogenes in a Mouse Model: Pyolysin Oligomerization and Structural Change Affect the Efficacy of Pyolysin-Based Vaccines , 2020, Vaccines.

[10]  Ting Huang,et al.  MTOR involved in bacterial elimination against Trueperella pyogenes infection based on mice model by transcriptome and biochemical analysis. , 2019, Veterinary microbiology.

[11]  M. Gieryńska,et al.  Pathogenicity and Virulence of Trueperella pyogenes: A Review , 2019, International journal of molecular sciences.

[12]  Ting Huang,et al.  TesG is a type I secretion effector of Pseudomonas aeruginosa that suppresses the host immune response during chronic infection , 2019, Nature Microbiology.

[13]  M. Raza,et al.  Interferon-gamma (IFN-γ): Exploring its implications in infectious diseases , 2018, Biomolecular concepts.

[14]  Ting Huang,et al.  Chitosan-DNA nanoparticles enhanced the immunogenicity of multivalent DNA vaccination on mice against Trueperella pyogenes infection , 2018, Journal of Nanobiotechnology.

[15]  B. Wang,et al.  A combined Clostridium perfringens/Trueperella pyogenes inactivated vaccine induces complete immunoprotection in a mouse model. , 2017, Biologicals : journal of the International Association of Biological Standardization.

[16]  Chunlian Tian,et al.  Trueperella pyogenes isolated from dairy cows with endometritis in Inner Mongolia, China: Tetracycline susceptibility and tetracycline-resistance gene distribution. , 2017, Microbial pathogenesis.

[17]  Ting Huang,et al.  Comparative transcriptome analysis of Trueperella pyogenes reveals a novel antimicrobial strategy , 2017, Archives of Microbiology.

[18]  W. Bielecki,et al.  Relationships between antimicrobial resistance, distribution of virulence factor genes and the origin of Trueperella pyogenes isolated from domestic animals and European bison (Bison bonasus). , 2016, Microbial pathogenesis.

[19]  Ting Huang,et al.  DNA vaccination based on pyolysin co-immunized with IL-1β enhances host antibacterial immunity against Trueperella pyogenes infection. , 2016, Vaccine.

[20]  M. Ribeiro,et al.  Trueperella pyogenes multispecies infections in domestic animals: a retrospective study of 144 cases (2002 to 2012) , 2015, The Veterinary quarterly.

[21]  O. Sandra,et al.  Differential Endometrial Cell Sensitivity to a Cholesterol-Dependent Cytolysin Links Trueperella pyogenes to Uterine Disease in Cattle1 , 2014, Biology of reproduction.

[22]  Xiaodi Yang,et al.  Protective immune response induced by co-immunization with the Trichinella spiralis recombinant Ts87 protein and a Ts87 DNA vaccine. , 2013, Veterinary parasitology.

[23]  Hongning Wang,et al.  Virulence determinants and biofilm production among Trueperella pyogenes recovered from abscesses of captive forest musk deer , 2013, Archives of Microbiology.

[24]  Y. Shao,et al.  Enhancement of HIV-1 DNA vaccine immunogenicity by BCG-PSN, a novel adjuvant. , 2013 .

[25]  H. Lassa,et al.  Genotypic characterization and evaluation of an antibiotic resistance of Trueperella pyogenes (Arcanobacterium pyogenes) isolated from milk of dairy cows with clinical mastitis. , 2012, Veterinary microbiology.

[26]  A. Ramsay,et al.  Prime–boost approaches to tuberculosis vaccine development , 2012, Expert review of vaccines.

[27]  Jing Sun,et al.  P02-08. Enhancement of HIV-1 DNA vaccine immunogenicity by BCG-PSN, a novel adjuvant , 2009, Vaccine.

[28]  S. J. Billington,et al.  Immunization with Genetic Toxoids of the Arcanobacterium pyogenes Cholesterol-Dependent Cytolysin, Pyolysin, Protects Mice against Infection , 2003, Infection and Immunity.

[29]  S. J. Billington,et al.  Molecular characterization of the pore-forming toxin, pyolysin, a major virulence determinant of Arcanobacterium pyogenes. , 2001, Veterinary microbiology.

[30]  J. Gouws,et al.  Failure of an Actinomyces pyogenes vaccine to protect sheep against an intravenous challenge. , 1990, The Onderstepoort journal of veterinary research.

[31]  Shailza Singh,et al.  Cytokine Milieu in Infectious Disease: A Sword or a Boon? , 2019, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[32]  M. P. Molinari,et al.  accine strategies against Babesia bovis based on prime-boost mmunizations in mice with modified vaccinia Ankara vector and ecombinant proteins osé , 2014 .