Positive immunomodulatory effects of heterologous DNA vaccine- modified live vaccine, prime-boost immunization, against the highly-pathogenic PRRSV infection

Sirisereewan, Chaitawat; Nedumpun, Teerawut; Kesdangsakonwut, Sawang; Woonwong, Yonlayong; Kedkovid, Roongtham; Arunorat, Jirapat; Thanawongnuwech, Roongroje; Suradhat, Sanipa

doi:10.1016/j.vetimm.2016.11.002

Cited by 17 publications

(15 citation statements)

References 34 publications

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“…Although these new approaches for PRRSV vaccines are still require much development, they show promise as alternative methods for boosting MLV-induced protection. A recent study showed that pre-immunization with a DNA vaccine encoding truncated PRRSV N protein 2 weeks prior to MLV immunization led to improved PRRSV-specific immunity (increased NA titers and increased PRRSV-specific IFN-γ production), with reduced IL-10 and PRRSV-specific Treg production during the challenge experiment ( Sirisereewan et al, 2017 ). Another study shows than immunization of pigs with a GP5 Mosaic T-cell DNA vaccine (codon-optimized mosaic sequences synthesized based on 748 independent PRRSV GP5 sequences) could evoke a higher virus-specific antibodies and IFN-γ mRNA expression, but still cannot confer full protection ( Cui et al, 2016 ).…”

Section: Current Licensed Prrsv Vaccines and Vaccines Under Developmementioning

confidence: 99%

Improved Vaccine against PRRSV: Current Progress and Future Perspective

et al. 2017

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Porcine reproductive and respiratory syndrome virus (PRRSV), one of the most economically significant pathogens worldwide, has caused numerous outbreaks during the past 30 years. PRRSV infection causes reproductive failure in sows and respiratory disease in growing and finishing pigs, leading to huge economic losses for the swine industry. This impact has become even more significant with the recent emergence of highly pathogenic PRRSV strains from China, further exacerbating global food security. Since new PRRSV variants are constantly emerging from outbreaks, current strategies for controlling PRRSV have been largely inadequate, even though our understanding of PRRSV virology, evolution and host immune response has been rapidly expanding. Meanwhile, practical experience has revealed numerous safety and efficacy concerns for currently licensed vaccines, such as shedding of modified live virus (MLV), reversion to virulence, recombination between field strains and MLV and failure to elicit protective immunity against heterogeneous virus. Therefore, an effective vaccine against PRRSV infection is urgently needed. Here, we systematically review recent advances in PRRSV vaccine development. Antigenic variations resulting from PRRSV evolution, identification of neutralizing epitopes for heterogeneous isolates, broad neutralizing antibodies against PRRSV, chimeric virus generated by reverse genetics, and novel PRRSV strains with interferon-inducing phenotype will be discussed in detail. Moreover, techniques that could potentially transform current MLV vaccines into a superior vaccine will receive special emphasis, as will new insights for future PRRSV vaccine development. Ultimately, improved PRRSV vaccines may overcome the disadvantages of current vaccines and minimize the PRRS impact to the swine industry.

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Section: Current Licensed Prrsv Vaccines and Vaccines Under Developmementioning

confidence: 99%

Improved Vaccine against PRRSV: Current Progress and Future Perspective

et al. 2017

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“…KEYWORDS CD83, NF-B, PRRSV, Sp1, nonstructural protein 10, nucleocapsid O ver the last 3 decades, porcine reproductive and respiratory syndrome virus (PRRSV) has become a serious threat to the swine industry worldwide (1,2). Current vaccines do not provide complete protection against this disease (3)(4)(5), and it is unclear how PRRSV inhibits the host's immune response and induces persistent infection.…”

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confidence: 99%

The Nucleocapsid Protein and Nonstructural Protein 10 of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Enhance CD83 Production via NF-κB and Sp1 Signaling Pathways

Chen

Zhang

Bai

et al. 2017

J Virol

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Porcine reproductive and respiratory syndrome, caused by porcine reproductive and respiratory syndrome virus (PRRSV), is a panzootic disease that is one of the most economically costly diseases to the swine industry. A key aspect of PRRSV virulence is that the virus suppresses the innate immune response and induces persistent infection, although the underlying mechanisms are not well understood. The dendritic cell (DC) marker CD83 belongs to the immunoglobulin superfamily and is associated with DC activation and immunosuppression of T cell proliferation when expressed as soluble CD83 (sCD83). In this study, we show that PRRSV infection strongly stimulates CD83 expression in porcine monocyte-derived DCs (MoDCs) and that the nucleocapsid (N) protein and nonstructural protein 10 (nsp10) of PRRSV enhance CD83 promoter activity via the NF-κB and Sp1 signaling pathways. R43A and K44A amino acid substitution mutants of the N protein suppress the N protein-mediated increase of CD83 promoter activity. Similarly, P192-5A and G214-3A mutants of nsp10 (with 5 and 3 alanine substitutions beginning at residues P192 and G214, respectively) abolish the nsp10-mediated induction of the CD83 promoter. Using reverse genetics, four mutant viruses (rR43A, rK44A, rP192-5A, and rG214-3A) and four revertants [rR43A(R), rK44A(R), rP192-5A(R), and rG214-3A(R)] were generated. Decreased induction of CD83 in MoDCs was observed after infection by mutants rR43A, rK44A, rP192-5A, and rG214-3A, in contrast to the results obtained using rR43A(R), rK44A(R), rP192-5A(R), and rG214-3A(R). These findings suggest that PRRSV N and nsp10 play important roles in modulating CD83 signaling and shed light on the mechanism by which PRRSV modulates host immunity. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically costly pathogens affecting the swine industry. It is unclear how PRRSV inhibits the host's immune response and induces persistent infection. The dendritic cell (DC) marker CD83 belongs to the immunoglobulin superfamily and has previously been associated with DC activation and immunosuppression of T cell proliferation and differentiation when expressed as soluble CD83 (sCD83). In this study, we found that PRRSV infection induces sCD83 expression in porcine MoDCs via the NF-κB and Sp1 signaling pathways. The viral nucleocapsid protein, nonstructural protein 1 (nsp1), and nsp10 were shown to enhance CD83 promoter activity. Amino acids R43 and K44 of the N protein, as well as residues 192 to 196 (P192-5) and 214 to 216 (G214-3) of nsp10, play important roles in CD83 promoter activation. These findings provide new insights into the molecular mechanism of immune suppression by PRRSV.

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“…Many commercial and experimental PRRSV KV have been evaluated, and the induced protective immunity may not be satisfactory [47]. In recent years, multiple novel strategies and techniques, such as the use of reverse genetics system, novel adjuvant or delivery way, diverse protein-expressing system, DNA vaccine platform, viral vector expression system, and T-cell epitope vaccine, are widely involved to design a novel PRRS vaccine to solve the "critical issues" of current commercial vaccines, such as variable heterologous cross-protection, reversion to virulence, recombination, and immunosuppression [160][161][162][163][164][165]. Many novel discoveries have been made with the potential to point out a new direction for PRRSV vaccinology, even though no new vaccine candidates are commercially available.…”

Section: Other Kinds Of Prrs Vaccinementioning

confidence: 99%

Porcine Reproductive and Respiratory Syndrome Modified Live Virus Vaccine: A “Leaky” Vaccine with Debatable Efficacy and Safety

Zhou

Yang

2021

Vaccines

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Porcine reproductive and respiratory syndrome (PRRS) caused by the PRRS virus (PRRSV) is one of the most economically important diseases, that has significantly impacted the global pork industry for over three decades, since it was first recognized in the United States in the late 1980s. Attributed to the PRRSV extensive genetic and antigenic variation and rapid mutability and evolution, nearly worldwide epidemics have been sustained by a set of emerging and re-emerging virus strains. Since the first modified live virus (MLV) vaccine was commercially available, it has been widely used for more than 20 years, for preventing and controlling PRRS. On the one hand, MLV can induce a protective immune response against homologous viruses by lightening the clinical signs of pigs and reducing the virus transmission in the affected herd, as well as helping to cost-effectively increase the production performance on pig farms affected by heterologous viruses. On the other hand, MLV can still replicate in the host, inducing viremia and virus shedding, and it fails to confer sterilizing immunity against PRRSV infection, that may accelerate viral mutation or recombination to adapt the host and to escape from the immune response, raising the risk of reversion to virulence. The unsatisfied heterologous cross-protection and safety issue of MLV are two debatable characterizations, which raise the concerns that whether it is necessary or valuable to use this leaky vaccine to protect the field viruses with a high probability of being heterologous. To provide better insights into the immune protection and safety related to MLV, recent advances and opinions on PRRSV attenuation, protection efficacy, immunosuppression, recombination, and reversion to virulence are reviewed here, hoping to give a more comprehensive recognition on MLV and to motivate scientific inspiration on novel strategies and approaches of developing the next generation of PRRS vaccine.

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Positive immunomodulatory effects of heterologous DNA vaccine- modified live vaccine, prime-boost immunization, against the highly-pathogenic PRRSV infection

Cited by 17 publications

References 34 publications

Improved Vaccine against PRRSV: Current Progress and Future Perspective

Improved Vaccine against PRRSV: Current Progress and Future Perspective

The Nucleocapsid Protein and Nonstructural Protein 10 of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Enhance CD83 Production via NF-κB and Sp1 Signaling Pathways

Porcine Reproductive and Respiratory Syndrome Modified Live Virus Vaccine: A “Leaky” Vaccine with Debatable Efficacy and Safety

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