Field porcine reproductive and respiratory syndrome viruses (PRRSV) attenuated by codon pair deoptimization (CPD) in NSP1 protected pigs from heterologous challenge

Park, Changhoon; Baek, Jong Hyuk; Cho, Sun Hee; Jeong, Jiwoon; Chae, Chanhee; You, Su-Hwa; Cha, Sang‐Ho

doi:10.1016/j.virol.2019.10.019

Cited by 19 publications

(38 citation statements)

References 42 publications

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“…These data support previous studies showing protection by NAs through two passive transfer experiments to be protective in pregnant sows [30] and partially protective in young, weaned pigs [31]. Yet, follow-on studies have examined the difficulty of achieving NAs through vaccinations that provide subsequent challenge protection against homologous and heterologous PRRSV strains in nursery pigs [32][33][34][35][36] and in gilts and sows [37][38][39][40]. These studies are often strain and age dependent but in general they reveal the following: the generation of serum NAs is delayed against PRRSV and titers are lower than in other common swine disease vaccinations, and cross-reactivity against heterologous PRRSV strains is limited.…”

Section: Discussionsupporting

confidence: 86%

Maternal Autogenous Inactivated Virus Vaccination Boosts Immunity to PRRSV in Piglets

et al. 2021

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Maternal-derived immunity is a critical component for the survival and success of offspring in pigs to protect from circulating pathogens such as Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2). The purpose of this study is to investigate the transfer of anti-PRRSV immunity to piglets from gilts that received modified-live virus (MLV) alone (treatment (TRT) 0), or in combination with one of two autogenous inactivated vaccines (AIVs, TRT 1+2). Piglets from these gilts were challenged with the autogenous PRRSV-2 strain at two weeks of age and their adaptive immune response (IR) was evaluated until 4 weeks post inoculation (wpi). The systemic humoral and cellular IR was analyzed in the pre-farrow gilts, and in piglets, pre-inoculation, and at 2 and 4 wpi. Both AIVs partially protected the piglets with reduced lung pathology and increased weight gain; TRT 1 also lowered piglet viremia, best explained by the AIV-induced production of neutralizing antibodies in gilts and their transfer to the piglets. In piglets, pre-inoculation, the main systemic IFN-γ producers were CD21α+ B cells. From 0 to 4 wpi, the role of these B cells declined and CD4 T cells became the primary systemic IFN-γ producers. In the lungs, CD8 T cells were the primary and CD4 T cells were the secondary IFN-γ producers, including a novel subset of porcine CD8α−CCR7− CD4 T cells, potentially terminally differentiated CD4 TEMRA cells. In summary, this study demonstrates that maternal AIV vaccination can improve protection of pre-weaning piglets against PRRSV-2; it shows the importance of transferring neutralizing antibodies to piglets, and it introduces two novel immune cell subsets in pigs—IFN-γ producing CD21α+ B cells and CD8α−CCR7− CD4 T cells.

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Section: Discussionsupporting

confidence: 86%

Maternal Autogenous Inactivated Virus Vaccination Boosts Immunity to PRRSV in Piglets

et al. 2021

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“…These data support previous studies showing protection by NAs through two passive transfer experiments to be protective in pregnant sows [29] and partially protective in young weaned pigs [30]. Yet, follow-on studies by Osorio and others have examined the difficulty of achieving NAs through vaccination that provide subsequent challenge protection against homologous and heterologous PRRSV strains in nursery pigs [31][32][33][34][35] and in gestational gilts / sows [36][37][38][39]. These studies are often strain and age dependent; but in general they reveal the following: Generation of serum NAs is delayed against PRRSV and titers are lower than in other common swine disease vaccinations; and cross-reactivity against heterologous PRRSV strains is limited.…”

Section: Discussionsupporting

confidence: 87%

Maternal Autogenous Inactivated Virus Vaccination Boosts the Piglet Humoral and Cell-Mediated Immunity to PRRSV via Transfer of Neutralizing Antibodies and Interferon-Gamma Producing B Cells

Kick¹,

Wolfe²,

Amaral³

et al. 2020

Preprint

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Maternal-derived immunity is a critical component for survival and success of offspring in pigs to protect from circulating pathogens like Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2). The purpose of this study was to investigate the transfer of anti-PRRSV immunity to piglets from gilts that received modified-live virus (MLV) alone (TRT 0), or in combination with one of two autogenous inactivated vaccines (AIVs, TRT 1+2). Piglets from these gilts were challenged with the autogenous PRRSV-2 strain at two weeks of age and their adaptive immune response (IR) was evaluated until 4 weeks post inoculation (wpi). The systemic humoral and cellular IR was analyzed in the pre-farrow gilts, and in piglets, pre-inoculation, and at 2- and 4-wpi. Both AIVs partially protected the piglets with reduced lung pathology and increased weight gain; TRT 1 also lowered piglet viremia best explained by the AIV-induced production of neutralizing antibodies in gilts and their transfer to the piglets. In piglets, pre-inoculation, the main systemic IFN-γ producers were CD21α+ B cells. From 0 to 4 wpi, the role of these B cells declined and CD4 T cells became the primary systemic IFN-γ producers. In lungs, CD8 T cells were the primary and CD4 T cells the secondary IFN-γ producers including a novel subset of porcine CD8α-CCR7- CD4 T cells, potentially terminally differentiated CD4 TEMRA cells. In summary, this study demonstrates that maternal AIV vaccination can improve protection of pre-weaning piglets against PRRSV-2; it shows the importance of transferring neutralizing antibodies to piglets; and it introduces two novel immune cell subsets in pigs – IFN-γ producing CD21α+ B cells and CD8α-CCR7- CD4 T cells.

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“…Thus, it is possible to incorporate a T7 RNA promoter between the CMV promoter and the viral genome to create a dual promoter that allows the flexibility of using both DNA and RNA transfection approaches [16]. To ensure the authenticity of the viral termini, hammerhead ribozyme and hepatitis delta virus ribozyme are, respectively, incorporated to the 5 and 3 end of the cDNA sequence in the DNA-based infectious clone [67,85]. It has been demonstrated that the DNA-based transfection system produces 10 to 100 fold higher viral titers than the RNA-based transfection system [85,86].…”

Section: Dna-based Transfection Approachmentioning

confidence: 99%

“…In the second approach, computational programs were employed to replace adjacent pairs of original codons of the PRRSV genes with the pairs of codons that are least frequently used; the process is known as codon-pair deoptimization [135]. Several experimental MLV vaccines have been generated through deoptimization of codon-pairs in nsp1, nsp9 and GP5 of different PRRSV strains [65][66][67]. The reported results are promising as the resulting PRRSV mutants were attenuated while still maintaining the ability to stimulate protective immunity when inoculated into pigs.…”

Section: Molecular Attenuationmentioning

confidence: 99%

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Porcine Reproductive and Respiratory Syndrome Virus Reverse Genetics and the Major Applications

Chaudhari

2020

Viruses

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Porcine reproductive and respiratory syndrome virus (PRRSV) is a positive sense, single-stranded RNA virus that is known to infect only pigs. The virus emerged in the late 1980s and became endemic in most swine producing countries, causing substantial economic losses to the swine industry. The first reverse genetics system for PRRSV was reported in 1998. Since then, several infectious cDNA clones for PRRSV have been constructed. The availability of these infectious cDNA clones has facilitated the genetic modifications of the viral genome at precise locations. Common approaches to manipulate the viral genome include site-directed mutagenesis, deletion of viral genes or gene fragments, insertion of foreign genes, and swapping genes between PRRSV strains or between PRRSV and other members of the Arteriviridae family. In this review, we describe the approaches to construct an infectious cDNA for PRRSV and the ten major applications of these infectious clones to study virus biology and virus–host interaction, and to design a new generation of vaccines with improved levels of safety and efficacy.

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Field porcine reproductive and respiratory syndrome viruses (PRRSV) attenuated by codon pair deoptimization (CPD) in NSP1 protected pigs from heterologous challenge

Cited by 19 publications

References 42 publications

Maternal Autogenous Inactivated Virus Vaccination Boosts Immunity to PRRSV in Piglets

Maternal Autogenous Inactivated Virus Vaccination Boosts Immunity to PRRSV in Piglets

Maternal Autogenous Inactivated Virus Vaccination Boosts the Piglet Humoral and Cell-Mediated Immunity to PRRSV via Transfer of Neutralizing Antibodies and Interferon-Gamma Producing B Cells

Porcine Reproductive and Respiratory Syndrome Virus Reverse Genetics and the Major Applications

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