Design of live-attenuated animal vaccines based on pseudorabies virus platform

Liu, Zhen; Kong, Zhengjie; Chen, Meng; Shang, Yue

doi:10.1186/s44149-022-00044-w

Cited by 4 publications

(1 citation statement)

References 117 publications

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“…The PRV Bartha-K61 strain was purchased from China Veterinary Culture Collection Center (Cat#CVCC AV249, Beijing, China) and was purified in BHK-21 cells. The green fluorescent protein (GFP)-tagged PRV (PRV-GFP) recombinant virus was generated previously ( Liu et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

Secondary metabolites of Bacillus subtilis L2 show antiviral activity against pseudorabies virus

Wang,

Hao,

Zhou

et al. 2023

Front. Microbiol.

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Bacillus subtilis (B. subtilis) is a commercially important probiotic known to produce secondary metabolites with antibacterial, antifungal and anti-inflammatory activities. However, the potential ability of B. subtilis to combat viruses, especially DNA viruses, has not been extensively investigated. In this study, we identified two distinct B. subtilis strains and examined the efficiency of their secondary metabolites against pseudorabies virus (PRV), a swine herpesvirus resulting in economic losses worldwide. We found that treatment with the secondary metabolites of B. subtilis L2, but not the metabolites of B. subtilis V11, significantly inhibited PRV replication in multiple cells. Notably, the antiviral activity of the metabolites of B. subtilis L2 was thermal stable, resistant to protease digestion. Moreover, these metabolites effectively impeded PRV binding, entry and replication. Importantly, oral administration of the metabolites of B. subtilis L2 protected mice from lethal PRV infection, rescuing weight loss and reducing the viral load in vivo. In summary, our results reveal that the metabolites of B. subtilis L2 exhibit anti-PRV activity both in vitro and in vivo, providing a potential candidate for novel antiviral drugs.

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Section: Methodsmentioning

confidence: 99%

Secondary metabolites of Bacillus subtilis L2 show antiviral activity against pseudorabies virus

Wang,

Hao,

Zhou

et al. 2023

Front. Microbiol.

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The attenuated Pseudorabies virus vaccine Bartha K61 induces a weak cellular immunity: implications for the development of PRV-vectored vaccines

Xing,

Li,

et al. 2024

Front. Immunol.

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Pseudorabies virus (PRV), causing Aujeszky’s disease in swine, has important economic impact on the pig industry in China and even poses a threat to public health. Although this disease has been controlled by vaccination with PRV live attenuated vaccines (LAVs), the potency of PRV LAVs in inducing cellular immunity has not been well characterized. In this study, using PRV Bartha K61 strain (BK61), the most-used PRV LAVs, as a model, we re-examined the cellular immune response elicited by the BK61 in mice and pigs by multicolor flow cytometry. We found that phenotypic activation of T cells, NK cells and B cells was hardly detected after vaccination. However, antigen-specific IFN-γ-producing CD4 T cells rather than CD8 T cells were dominantly detected but at low frequency upon restimulation with live BK61 virus. These BK61-specific CD4 T cells are also able to simultaneously produce TNF-α and IL-2, showing characteristics of multifunctional T cells. However, BK61-specific CD4 T cells showed weak secondary response upon challenge with PRV DX strain. Further vaccination with PRV-infected dendritic cells (DCs) transiently increased the percentage of IFN-γ-positive CD4 and CD8 T cells but eventually restored to low frequency and did not improve the protective efficacy of BK61 against challenge, suggesting that PRV BK61 induced a relatively weak cellular immunity that could not be overcome by the DC vaccination. Similar immune responses were also observed following vaccination with another PRV LAV HD/c in mice and pigs, suggesting that this may be an intrinsic drawback of PRV LAVs in inducing cellular immunity. Our results demonstrated that PRV LAVs elicited a CD4 Th1-biased weak cellular immunity which is implicative for the development of PRV-vectored vaccine.

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Exploring Prime-Boost Vaccination Regimens with Different H1N1 Swine Influenza A Virus Strains and Vaccine Platforms

et al. 2022

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In a previous vaccination study in pigs, heterologous prime-boost vaccination with whole-inactivated H1N1 virus vaccines (WIV) induced superior antibody responses and protection compared to homologous prime-boost vaccination. However, no pan-H1 antibody response was induced. Therefore, to stimulate both local and systemic immune responses, we first vaccinated pigs intranasally with a pseudorabies vector vaccine expressing the pH1N1 hemagglutinin (prvCA09) followed by a homologous or heterologous WIV booster vaccine. Homologous and heterologous WIV–WIV vaccinated groups and mock-vaccinated or prvCA09 single-vaccinated pigs served as control groups. Five weeks after the second vaccination, pigs were challenged with a homologous pH1N1 or one of two heterologous H1N2 swine influenza A virus strains. A single prvCA09 vaccination resulted in complete protection against homologous challenge, and vector–WIV vaccinated groups were significantly better protected against heterologous challenge compared to the challenge control group or WIV–WIV vaccinated groups. Furthermore, vector–WIV vaccination resulted in broader hemagglutination inhibition antibody responses compared to WIV–WIV vaccination and higher numbers of antibody-secreting cells in peripheral blood, draining lymph nodes and nasal mucosa. However, even though vector–WIV vaccination induced stronger antibody responses and protection, we still failed to induce a pan-H1 antibody response.

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Design of live-attenuated animal vaccines based on pseudorabies virus platform

Cited by 4 publications

References 117 publications

Secondary metabolites of Bacillus subtilis L2 show antiviral activity against pseudorabies virus

Secondary metabolites of Bacillus subtilis L2 show antiviral activity against pseudorabies virus

The attenuated Pseudorabies virus vaccine Bartha K61 induces a weak cellular immunity: implications for the development of PRV-vectored vaccines

Exploring Prime-Boost Vaccination Regimens with Different H1N1 Swine Influenza A Virus Strains and Vaccine Platforms

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