Immunogenic and protective properties of GP5 and M structural proteins of porcine reproductive and respiratory syndrome virus expressed from replicating but nondisseminating adenovectors

Roques, Élodie; Girard, Aurélie; St-Louis, Marie-Claude; Massie, Bernard; Gagnon, Carl A.; Lessard, Martin; Archambault, Denis

doi:10.1186/1297-9716-44-17

Cited by 21 publications

(9 citation statements)

References 65 publications

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“…After 20, 24 or 26 weeks, Groups 1 and 2 were challenged with a heterologous European PRRS viral isolate 205,817, which shared 88.3% sequence homology at the GP5 gene with Ingelvac PRRSFLEX® EU. The GP5 gene encodes the major envelope protein of PRRSV, and carries the major neutralising epitope of PRRSV [ 28 ]. Groups 1 and 2 were subsequently evaluated for lung pathology, serum and lung viremia, and observed for clinical signs of disease.…”

Section: Discussionmentioning

confidence: 99%

Long duration of immunity against a type 1 heterologous PRRS virus challenge in pigs immunised with a novel PRRS MLV vaccine: a randomised controlled study

et al. 2018

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BackgroundPorcine reproductive and respiratory syndrome virus (PRRSV) is widespread in commercial pig farms worldwide, and has a significant cost to the swine industry. Herd owners need a vaccine that will confer long-lasting immunity to prevent PRRSV infection and transmission. The studies described here evaluated duration of immunity conferred by a European-derived PRRS (isolate 94,881) modified live virus (MLV) vaccine, Ingelvac PRRSFLEX® EU, at 20, 24, and 26 weeks post-vaccination. Primary endpoints were the assessment of gross and histological lung lesions and viral RNA load in lung tissue 10 days following heterologous PRRSV challenge. Secondary endpoints included clinical observations, average daily weight gain (ADWG) and viral RNA load in serum 10 days post-challenge. Three blinded, vaccination-challenge efficacy studies were performed using separate cohorts of pigs (n = 56 per study). Pigs received either Ingelvac PRRSFLEX® EU (Group 1) or placebo (Groups 2 and 3). Groups 1 and 2 were subsequently challenged with heterologous European PRRSV isolate 205,817 at 20, 24 or 26 weeks post-vaccination.ResultsMean gross lung lesion scores were significantly lower in Group 1 than in Group 2 at 24 and 26 weeks (p < 0.0001), but not at 20 weeks (p = 0.299). Significantly lower mean histological lung lesion scores were observed in Group 1 versus Group 2 at 20 (p = 0.0065), 24 (p < 0.0001) and 26 weeks (p < 0.0001). Mean viral RNA load in lung tissue was significantly lower in Group 1 than in Group 2 (p < 0.0001) at 20 (p < 0.0001), 24 (p < 0.0001) and 26 weeks (p < 0.0001). Cumulative viral RNA loads in serum during days 1–10 post-challenge were significantly lower in Group 1 than in Group 2 (p < 0.0001) in all studies. A significant increase in ADWG was observed in Group 1 compared with Group 2 at 20 weeks (p = 0.0027) and 24 weeks (p = 0.0004), but not at 26 weeks (p = 0.1041). There were no significant differences in clinical signs post-challenge in any study.ConclusionThese results suggest that Ingelvac PRRSFLEX® EU confers long-term immunity to European heterologous PRRSV, which is maintained up to 26 weeks after vaccination, corresponding to the expected lifespan of commercial pigs.

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Section: Discussionmentioning

confidence: 99%

Long duration of immunity against a type 1 heterologous PRRS virus challenge in pigs immunised with a novel PRRS MLV vaccine: a randomised controlled study

et al. 2018

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“…The reason for the higher SVN antibody induction in these CV groups might be due to the ORFs 3–4 and ORFs 5–6 from K08-1054 and K07-2273, respectively [ 22 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. Notably, a major role for ORFs 5–6 in virus neutralization has been examined in previous studies [ 10 , 39 , 44 , 46 , 47 , 48 , 49 , 50 ], which might explain the high SVN antibody induction in CV/K07-2273 against K07-2273. However, in this study, CV/K07-2273 exhibited nine-fold higher SVN antibody titers against K07-2273 compared with the antibody titers induced in the homologous group (K07-2273/K07-2273), indicating a possible role for the CV backbone in SVN antibody induction.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Cross-Protective Efficacy of a Chimeric Porcine Reproductive and Respiratory Syndrome Virus Constructed Based on Two Field Strains

Shabir

Khatun

Nazki

et al. 2016

Viruses

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One of the major hurdles to porcine reproductive and respiratory syndrome (PRRS) vaccinology is the limited or no cross-protection conferred by current vaccines. To overcome this challenge, a PRRS chimeric virus (CV) was constructed using an FL12-based cDNA infectious clone in which open reading frames (ORFs) 3–4 and ORFs 5–6 were replaced with the two Korean field isolates K08-1054 and K07-2273,respectively. This virus was evaluated as a vaccine candidate to provide simultaneous protection against two genetically distinct PRRS virus (PRRSV) strains. Thirty PRRS-negative three-week-old pigs were divided into five groups and vaccinated with CV, K08-1054, K07-2273, VR-2332, or a mock inoculum. At 25 days post-vaccination (dpv), the pigs in each group were divided further into two groups and challenged with either K08-1054 or K07-2273. All of the pigs were observed until 42 dpv and were euthanized for pathological evaluation. Overall, the CV-vaccinated group exhibited higher levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin-12 (IL-12) expression and of serum virus-neutralizing antibodies compared with the other groups after vaccination and also demonstrated better protection levels against both viruses compared with the challenge control group. Based on these results, it was concluded that CV might be an effective vaccine model that can confer a broader range of cross-protection to various PRRSV strains.

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“…However, recombinant GP5 protein was poorly immunogenic, failed to provide protection, and even exacerbated disease upon challenge ( 16 ). Expression of GP5 using plasmid DNA or viral vectors, alone or in conjunction with other structural proteins, have shown variable immunogenicity and at best confer a limited degree of protection ( 17 – 21 ). The limitations of existing and experimental vaccines support the investigation of novel approaches to PRRSV vaccine development.…”

Section: Introductionmentioning

confidence: 99%

The Non-structural Protein 5 and Matrix Protein Are Antigenic Targets of T Cell Immunity to Genotype 1 Porcine Reproductive and Respiratory Syndrome Viruses

et al. 2016

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The porcine reproductive and respiratory syndrome virus (PRRSV) is the cause of one of the most economically important diseases affecting swine worldwide. Efforts to develop a next-generation vaccine have largely focused on envelope glycoproteins to target virus-neutralizing antibody responses. However, these approaches have failed to demonstrate the necessary efficacy to progress toward market. T cells are crucial to the control of many viruses through cytolysis and cytokine secretion. Since control of PRRSV infection is not dependent on the development of neutralizing antibodies, it has been proposed that T cell-mediated immunity plays a key role. Therefore, we hypothesized that conserved T cell antigens represent prime candidates for the development a novel PRRS vaccine. Antigens were identified by screening a proteome-wide synthetic peptide library with T cells from cohorts of pigs rendered immune by experimental infections with a closely related (subtype 1) or divergent (subtype 3) PRRSV-1 strain. Dominant T cell IFN-γ responses were directed against the non-structural protein 5 (NSP5), and to a lesser extent, the matrix (M) protein. The majority of NSP5-specific CD8 T cells and M-specific CD4 T cells expressed a putative effector memory phenotype and were polyfunctional as assessed by coexpression of TNF-α and mobilization of the cytotoxic degranulation marker CD107a. Both antigens were generally well conserved among strains of both PRRSV genotypes. Thus, M and NSP5 represent attractive vaccine candidate T cell antigens, which should be evaluated further in the context of PRRSV vaccine development.

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Immunogenic and protective properties of GP5 and M structural proteins of porcine reproductive and respiratory syndrome virus expressed from replicating but nondisseminating adenovectors

Cited by 21 publications

References 65 publications

Long duration of immunity against a type 1 heterologous PRRS virus challenge in pigs immunised with a novel PRRS MLV vaccine: a randomised controlled study

Long duration of immunity against a type 1 heterologous PRRS virus challenge in pigs immunised with a novel PRRS MLV vaccine: a randomised controlled study

Evaluation of the Cross-Protective Efficacy of a Chimeric Porcine Reproductive and Respiratory Syndrome Virus Constructed Based on Two Field Strains

The Non-structural Protein 5 and Matrix Protein Are Antigenic Targets of T Cell Immunity to Genotype 1 Porcine Reproductive and Respiratory Syndrome Viruses

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