Immunobiology of pseudorabies (Aujeszky's Disease)

doi:10.1016/S0165-2427(96)05695-4

Veterinary Immunology and Immunopathology

Volume 54, Issues 1–4, November 1996, Pages 221-229

https://doi.org/10.1016/S0165-2427(96)05695-4 Get rights and content

Abstract

Aujeszky's Disease (AD), a serious illness of pigs causing significant economic losses in the pig industry, is caused by Pseudorabies Virus (PrV). PrV belongs to the alphaherpesvirus subfamiliy of the herpesviruses with a double-stranded DNA genoe in an enveloped capsid capable of encoding approximately 70 proteins. For disease control, vaccination with live and killed vaccines is performed. Recently, ‘marked’ vaccines have become available for use in eradication programs based on the differentiation between infected and vaccinated animals. PrV is also used as a viral vector for the development of multivalent vaccines. Despite the effectiveness of PrV vaccines, relatively little is known about the immune response against PrV infection. Several viral envelope glycoproteins have been shown to represent targets for antibody responses, and a number of isolated glycoproteins as well as genetically engineered proteins were able to elicit protective immunity. The nature of the cellular immune response is even less defined. Using viral mutants genetically engineered to lack specific antigens, it has been shown that glycoprotein C (gC) acts as a target for cytotoxic T-lymphocytes, and gB, gC, gD, and gH appear to be involved in stimulation of in vitro proliferation of PBMC from immune animals. In addition, gB and gC have been implicated in recognition of infected cells by lymphokine-activated killer (LAK) cells. In summary, the data indicate a prominent role for viral envelope glycoproteins in eliciting humoral and cellular immune responses in the animal host. A complicating factor is the ability of PrV to productively infect cells of the hematopoietic system, which may impair immune responses and might also play a role in persistent or latent infection.

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Pseudorabies virus (PRV) mainly causes pseudorabies (PR) or Aujeszky's disease in pigs and can infect humans, raising public health concerns about zoonotic and interspecies transmission of PR. With the emergence of PRV variants in 2011, the classic attenuated PRV vaccine strains have failed to protect many swine herds against PR. Herein, we developed a self-assembled nanoparticle vaccine that induces potent protective immunity against PRV infection. PRV glycoprotein D (gD) was expressed using the baculovirus expression system and further presented on the lumazine synthase (LS) 60-meric protein scaffolds via the SpyTag003/SpyCatcher003 covalent coupling system. In mouse and piglet models, LSgD nanoparticles emulsified with the ISA 201VG adjuvant elicited robust humoral and cellular immune responses. Furthermore, LSgD nanoparticles provided effective protection against PRV infection and eliminated pathological symptoms in the brain and lungs. Collectively, the gD-based nanoparticle vaccine design appears to be a promising candidate for potent protection against PRV infection.
Better immune efficacy triggered by the inactivated gI/gE-deleted pseudorabies virus with the additional insertion of gC gene in mice and weaned pigs
2021, Virus Research
A new variant of pseudorabies virus (PRV) with high pathogenicity has been prevalent in many swineherds vaccinated with Bartha-K61 in China since 2011. Several gene-deleted vaccine candidates have been developed based on new emerging PRV variants. PRV-AH, a new emerging PRV strain from Anhui Province, was isolated in our laboratory in 2013. In the present study, rPRV-AH-gI⁻/gE⁻ and rPRV-AH-gI⁻/gE⁻/gC⁺ were generated based on PRV-AH by homologous recombination. The growth kinetics of rPRV-AH-gI⁻/gE⁻ and rPRV-AH-gI⁻/gE⁻/gC⁺ were similar to their parental strains. Compared with the commercial inactivated vaccine of Ea strain, the immune efficacy of the inactivated vaccine based on recombinant viruses was evaluated in mice and weaned pigs. The result showed that the level of neutralizing antibody in mice immunized with rPRV-AH-gI⁻/gE⁻/gC⁺ was higher compared with those immunized with rPRV-AH-gI⁻/gE- at a dose of 10⁶ TCID₅₀ at 8 weeks post initial immunization (p < 0.0001). Among the groups immunized at a dose of 10⁵ TCID₅₀, the rPRV-AH-gI⁻/gE⁻ group showed a survival rate of 37.5 %, while the rPRV-AH-gI⁻/gE⁻/gC⁺ group showed a protection rate of 87.5 % against the PRV-AH challenge. Besides, the rPRV-AH-gI⁻/gE⁻ and rPRV-AH-gI⁻/gE⁻/gC⁺ group immunized at a dose of 10⁶ TCID₅₀ showed a survival rate of 100 %. Interestingly, compared with the commercial vaccine group, the group of 10⁵ TCID₅₀ rPRV-AH-gI⁻/gE⁻/gC⁺ showed a lower level of neutralizing antibodies (p < 0.0001) but the same protection rate in mice. Moreover, in the pig experiment, the level of neutralizing antibodies in the group vaccinated with inactivated rPRV-AH-gI⁻/gE⁻/gC⁺ was higher than any other groups at 8 weeks post initial immunization (p < 0.05). More importantly, the milder symptoms and pathological lesions occurred in pigs vaccinated with rPRV-AH-gI⁻/gE⁻/gC⁺ after challenge with 10⁶ TCID₅₀ PRV-AH, revealing that additional insertion of gC gene could enhance the protective efficacy in PRV gI/gE-deleted vaccine in pigs. Collectively, these above-mentioned findings suggested that the inactivated vaccine of rPRV-AH-gI⁻/gE⁻/gC⁺ had a better immune efficacy, which could be regarded as a promising inactivated vaccine candidate for PRV control.
Evidence for interspecies transmission route of pseudorabies virus via virally contaminated fomites
2020, Veterinary Microbiology
Pseudorabies virus (PRV) is a zoonotic agent with a wide host range, causing significant economic losses in animal husbandry and potential public health risk globally. The causative agent has recently gained attention due to the inter-species transmission among different species of animals, even human beings. Although PRV's prevalence is found in many species of animals, regardless of whether the strain involved is a vaccine, classical or variant, few lines of evidence for the viral transmission route are available. Here, we reported that viral contamination is associated with the inter-species transmission of PRV. We found that PRV contamination was widely distributed in the environment of pig farms, that viral distribution in the environment is associated with the implementation of biosecurity measures, and that PRV could transmit from pigs to dogs through virally contaminated fomites. Collectively, our findings provide a basis for understanding the ecology and transmission route of PRV and underscore the importance of implementing biosecurity measures to control this disease.
Construction and immunogenicity of a gE/gI/TK-deleted PRV based on porcine pseudorabies virus variant
2020, Molecular and Cellular Probes
Pseudorabies (PR) caused by re-emerging pseudorabies virus (PRV) variant has outbroken among PRV vaccine-immunized swine herds on many Chinese pig farms, with severe socioeconomic consequences since late 2011. Here, a gE/gI/TK-deleted recombinant virus (rPRV NY-gE⁻/gI⁻/TK⁻) was constructed based on PRV NY strain from 2012 through homologous DNA recombination and gene-editing technology termed clustered regularly interspaced palindromic repeats (CRISPR)/associated (Cas9) system. The rPRV NY-gE⁻/gI⁻/TK⁻ strain showed similar growth kinetics to the parental PRV NY strain in vitro, and was safe for mice. Sixty mice were injected subcutaneously (s.c.) twice with 10^6.0 TCID₅₀ of rPRV NY-gE⁻/gI⁻/TK⁻ and DMEM, respectively, with two-week interval. The levels of PRV gB antibodies and neutralizing antibodies against PRV NY in mice immunized with rPRV NY-gE⁻/gI⁻/TK⁻ were higher than those in the DMEM control group. The number of T lymphocyte subclasses CD3⁺, CD4⁺ and CD8⁺ in rPRV NY-gE⁻/gI⁻/TK⁻-immunized mice was higher than that in DMEM-injected mice. After challenge with 10^6.0 TCID₅₀ PRV NY at 42 dpi, all rPRV NY-gE⁻/gI⁻/TK⁻-immunized mice survived without exhibiting any pathological lesions in different tissues and intranuclear eosinophilic inclusions of the brain, and the viral genomic copy numbers in various organs of mice were obviously lower than DMEM group. These results showed the rPRV NY-gE⁻/gI⁻/TK⁻ could be a promising next-generation vaccine to control now epidemic PR in China.
Fusion of pseudorabies virus glycoproteins to IgG Fc enhances protective immunity against pseudorabies virus
2019, Virology
Citation Excerpt :
There are at least 11 different glycoproteins (gB, gC, gD, gE, gG, gH, gI, gK, gL, gM, or gN) of PRV that so far have been identified (Dong et al., 2014). Among the different glycoproteins of PRV, gB, gC, and gD are the most important for the development of the antiviral humoral and cellular immune response (Mettenleiter, 1996; Mukamoto et al., 1991). Interestingly, previous studies have shown that regardless of systemic or mucosal administration, recombinant adenoviruses expressing gB or gD could confer the most effective protection against a lethal viral challenge (Han et al., 2008).
Molecular adjuvants are vaccine delivery vehicle to increase specific antigens effectiveness. Herein, we concentrated on IgG Fc, an effective molecular adjuvant, to develop novel pseudorabies virus (PRV) subunit vaccines. Two major protective antigen genes of PRV were constructed and linked into the mouse IgG Fc fragment. The gD, gD-IgG2aFc, gB and gB-IgG2aFc proteins were expressed using a baculovirus system. Mice intranasally immunized with gD-IgG2aFc or gB-IgG2aFc subunit vaccine exhibited significantly higher PRV-specific antibodies, neutralizing antibodies and intracellular cytokines than the mice intranasally immunized with gD or gB subunit vaccine. Moreover, no histopathological lesions were observed in mice immunized with gB-IgG2aFc subunit vaccine via histopathology examination. Further, the gB-IgG2aFc subunit vaccine was efficient for PRV infection compared with live attenuated vaccine. Overall, these results suggest that IgG2a Fc fragment, as a potential molecular adjuvant, fused with PRV antigen might be a promising and efficient PRV vaccine candidate.
Commercial vaccine against pseudorabies virus: A hidden health risk for dogs
2019, Veterinary Microbiology
Pseudorabies virus (PRV) is considered as an infectious agent with a wide of host range, causing considerable economic losses in animal husbandry. Although the commercial vaccine against PRV plays an critical role in control of this disease in swine industry, the potential risk of commercial vaccines against PRV for other host is unclear. Here, we report that the commercial vaccine against PRV is a hidden health risk for dogs. We found that different attenuated PRV strains in commercial vaccines possess different tissue tropism, and that the attenuated PRV strains are lethal to dogs, and that the attenuated PRV strain possesses the ability to spread horizontally among the dogs. Collectively, our findings provide clues that the commercial vaccine against PRV is a hidden risk for dogs, even for the owner of pet dogs to take seriously.

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Immunobiology of pseudorabies (Aujeszky's Disease)

Abstract

Virology

Vet. Immunol. Immunopathol.

Virus Res.

Vaccine

Vet. Microbiol.

Vet. Microbiol.

J. Comp. Pathol.

Vaccine

J. Virol.

Mag. Allat. Lapja

Arch. Virol.

Arch. Virol.

J. Virol.

J. Gen. Virol.

J. Virol.

J. Virol.

J. Leukocyte Biol.

Arch. Virol.

J. Gen. Virol.

Am. J. Vet. Res.

J. Virol.

J. Virol.