A Combinatorial Vaccine Containing Inactivated Bacterin and Subunits Provides Protection Against Actinobacillus pleuropneumoniae Infection in Mice and Pigs

Zhang, Lijun; Luo, Wentao; Xiong, Ruisheng; Li, Haotian; Yao, Zhiming; Zhuo, Wenxiao; Zou, Geng; Huang, Qi; Zhou, Rui

doi:10.3389/fvets.2022.902497

Cited by 5 publications

(6 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several proteins with key roles in A. pleuropneumoniae pathobiology, are all controlled by different phasevarions. These proteins include the major RTX toxins (ApxIVA, ApxIIIA and ApxIIIC) ( 81–83 ), several outer membrane proteins ( 83 ) and proteins involved in lipooligosaccharide and capsule biosynthesis ( 84 ), implying a complex mode of regulation of these factors, and raising questions about their suitability for use in vaccines against A. pleuropneumoniae . Inclusion of phase-variable proteins as components of subunit vaccines has previously been discounted, as variable expression of vaccine targets could lead to a decrease in vaccine efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…Inclusion of phase-variable proteins as components of subunit vaccines has previously been discounted, as variable expression of vaccine targets could lead to a decrease in vaccine efficacy. As we identify several proteins in multiple phasevarions that are A. pleuropneumoniae vaccine candidates, including the Apx toxins ( 81–83 ), it is critical to understand the exact mode of regulation of these proteins in order to direct and inform vaccine subunit vaccine development.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Actinobacillus pleuropneumoniae encodes multiple phase-variable DNA methyltransferases that control distinct phasevarions

Nahar

Tram

Jen

et al. 2023

Nucleic Acids Research

View full text Add to dashboard Cite

Actinobacillus pleuropneumoniae is the cause of porcine pleuropneumonia, a severe respiratory tract infection that is responsible for major economic losses to the swine industry. Many host-adapted bacterial pathogens encode systems known as phasevarions (phase-variable regulons). Phasevarions result from variable expression of cytoplasmic DNA methyltransferases. Variable expression results in genome-wide methylation differences within a bacterial population, leading to altered expression of multiple genes via epigenetic mechanisms. Our examination of a diverse population of A. pleuropneumoniae strains determined that Type I and Type III DNA methyltransferases with the hallmarks of phase variation were present in this species. We demonstrate that phase variation is occurring in these methyltransferases, and show associations between particular Type III methyltransferase alleles and serovar. Using Pacific BioSciences Single-Molecule, Real-Time (SMRT) sequencing and Oxford Nanopore sequencing, we demonstrate the presence of the first ever characterised phase-variable, cytosine-specific Type III DNA methyltransferase. Phase variation of distinct Type III DNA methyltransferase in A. pleuropneumoniae results in the regulation of distinct phasevarions, and in multiple phenotypic differences relevant to pathobiology. Our characterisation of these newly described phasevarions in A. pleuropneumoniae will aid in the selection of stably expressed antigens, and direct and inform development of a rationally designed subunit vaccine against this major veterinary pathogen.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Actinobacillus pleuropneumoniae encodes multiple phase-variable DNA methyltransferases that control distinct phasevarions

Nahar

Tram

Jen

et al. 2023

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…Several proteins with key roles in A. pleuropneumoniae pathobiology, are all controlled by different phasevarions. These proteins include the major RTX toxins (ApxIVA, ApxIIIA and ApxIIIC) (78)(79)(80), several outer membrane proteins (80) and proteins involved in LOS and capsule biosynthesis (81), implying a complex mode of regulation of these factors, and raising questions about their suitability for use in vaccines against A. pleuropneumoniae. Inclusion of phase-variable proteins as components of subunit vaccines has previously been discounted, as variable expression of vaccine targets could lead to a decrease in vaccine efficacy.…”

Section: Discussionmentioning

confidence: 99%

Actinobacillus pleuropneumoniaeencodes multiple phase-variable DNA methyltransferases that comprise distinct phasevarions

Nahar

Tram

Jen

et al. 2022

Preprint

View full text Add to dashboard Cite

Actinobacillus pleuropneumoniae is the cause of porcine pleuropneumonia, a severe respiratory tract infection that is responsible for major economic losses to the swine industry. Many host-adapted bacterial pathogens encode systems known as phasevarions (phase-variable regulons). Phasevarions result from variable expression of cytoplasmic DNA methyltransferases. Variable expression results in genome-wide methylation differences within a bacterial population, leading to altered expression of multiple genes via epigenetic mechanisms. Our examination of a diverse population of A. pleuropneumoniae strains determined that Type I and Type III DNA methyltransferases with the hallmarks of phase variation were present in this species. We demonstrate that phase variation is occurring in these methyltransferase, and show associations between particular Type III methyltransferase alleles and serovar. Using Pacific BioSciences Single-Molecule, Real-Time (SMRT) sequencing and Oxford Nanopore sequencing, we demonstrate the presence of the first ever characterised phase-variable, cytosine-specific Type III DNA methyltransferase. Phase variation of distinct Type III DNA methyltransferase variants results in the regulation of distinct phasevarions, and in multiple phenotypic differences relevant to pathobiology. Our characterisation of these newly described phasevarions in A. pleuropneumoniae will aid in the selection of stably expressed antigens, and direct and inform development of a rationally designed subunit vaccine against this major veterinary pathogen.

show abstract

“…A subunit vaccine was then developed, it is mainly based on the conserved virulent toxins and outer membrane proteins (OMPs). But it exhibit partial cross-protection [4,5], effective A. pleuropneumoniae vaccine protection can be provided by multi-component protein single target vaccines will increase protective immunity in subunit vaccine [6] . To date, a pathogen comprising 19 serotypes of A. pleuropneumoniae have been identified worldwide [7].…”

Section: Introductionmentioning

confidence: 99%

Immune Response to the Dual Antigen Vaccine of Actinobacillus pleuropneumoniae in a Mouse Model

Chuekwon,

Cheng

2023

Trends Sci

View full text Add to dashboard Cite

Actinobacillus pleuropneuminiae is the major cause of invasive respiratory disease in swine. To develop an efficient subunit vaccine against pathogens, we designed a dual antigen in a single vaccine that increased the potential for an immune response. We present a dual antigen vaccine (pore-forming domain and nutritional immunity) that induces humoral and cell-mediated T-cell responses, antibodies and TH1 and TH2 cells. Mice were immunized with the dual antigen and individual antigen and then subjected to immune response analysis. A significant antibody response was observed for the dual antigen group. For the cellular immune response, CD4+ and CD8+ T-cell expansion, proinflammatory cytokine (IL-1b, IL-6) and TH2-type cytokine (IL-4, IL-10) gene expression was observed for the dual antigen. Finally, in a challenge test with A. pleuropneumoniae serotype1, the dual antigen, individual antigen and PBS vaccine conferred 100, 40 and 0 % protection. In conclusion, the dual antigen presents critical antigens and increases the efficacy of the vaccine. HIGHLIGHTS The dual antigen vaccine of Actinobacillus pleuropneumonia (ApxII pore - forming domain and TonB2-the nutritional immunity antigen) were formulated as vaccines Mice were vaccinated, immune response analysis and challenge test were performed significant antibody response was observed and improved by approximately 2.5-fold for the dual antigen groups CD4 + and CD8 + T cell expansion was observed for the dual antigen group Protection rate of 100 %, 40 %, and 0 % was observed for the dual antigen, single antigen and negative control groups, respectively GRAPHICAL ABSTRACT

show abstract

A Combinatorial Vaccine Containing Inactivated Bacterin and Subunits Provides Protection Against Actinobacillus pleuropneumoniae Infection in Mice and Pigs

Cited by 5 publications

References 34 publications

Actinobacillus pleuropneumoniae encodes multiple phase-variable DNA methyltransferases that control distinct phasevarions

Actinobacillus pleuropneumoniae encodes multiple phase-variable DNA methyltransferases that control distinct phasevarions

Actinobacillus pleuropneumoniaeencodes multiple phase-variable DNA methyltransferases that comprise distinct phasevarions

Immune Response to the Dual Antigen Vaccine of Actinobacillus pleuropneumoniae in a Mouse Model

Contact Info

Product

Resources

About