Anti-idiotypic antibodies reduce efficacy of the attenuated vaccine against highly pathogenic PRRSV challenge

Yu, Ying; Cai, Xuehui; Wang, Gang; Kong, Ning; Liu, Yonggang; Xiao, Yihong; Zhang, Chong; Yang, Mei; Xiao, Shuqi; Zhao, Qin; Wang, Chengbao; Zhang, Gaiping; Hiscox, Julian A.

doi:10.1186/1746-6148-10-39

Cited by 10 publications

(8 citation statements)

References 42 publications

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“…4a ). Nonetheless, CH-1R strain can offer protection against clinical disease after HP-PRRSV HuN4 infection, and this observation is consistent with our previously published work [ 50 , 51 ]. Therefore, the role of IFN-γ in the process of the immune protection to CH-1R vaccination is not clear and need further investigation.…”

Section: Discussionsupporting

confidence: 93%

Rescue and evaluation of a recombinant PRRSV expressing porcine Interleukin-4

Wang

et al. 2015

Virol J

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BackgroundThe current vaccines for porcine reproductive and respiratory syndrome virus (PRRSV) have failed to provide broad protection against infection by various strains of PRRSV. Porcine Interleukin-4 (pIL-4) plays an important role in the regulation of the immune response and has been used previously as an immunological adjuvant. The objective of this study was to construct a recombinant PRRSV expressing pIL-4 and to evaluate the immune response of the recombinant virus in piglets.MethodsThe pIL-4 gene was inserted in the PRRSV (CH-1R strain) infectious clone by overlap PCR. Indirect immunofluorescence assay (IFA) and Western blotting were used to confirm the recombinant virus. The stability of the recombinant virus was assessed by DNA sequencing and IFA after 15 passages in vitro. Recombinant virus was injected into pigs and efficacy of immune protection was evaluated in comparison with the parental virus.ResultsThe recombinant virus (CH-1R/pIL-4) was successfully rescued and shown to have similar growth kinetics as the parental virus. The recombinant virus was stable for 15 passages in cell culture. Pigs vaccinated with CH-1R/pIL-4 produced a similar humoral response to the response elicited by parental virus, but IL-4 level in the supernatant of PBMCs from pigs vaccinated with CH-1R/pIL-4 was significantly higher than the parent virus at 28 days post-immunization (DPI). Flow cytometric (FCM) analysis showed that the percentage of CD4+CD8+ double positive T (DPT) cells in the CH-1R/pIL-4 vaccinated group was significantly higher than the parental virus at 3 and 7 Days Post-Challenge (DPC), and the IL-4 level in the blood significantly increased at 7 DPC. However, the viral load and histopathology did not show significant difference between the two groups.ConclusionsA recombinant PRRSV expressing porcine IL-4 was rescued and it remained genetically stable in vitro. The recombinant virus induced higher DPT ratios and IL-4 levels in the blood after HP-PRRSV challenge compared to the parental virus in piglets. However, it did not significantly improve protection efficacy of PRRSV vaccine.

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Section: Discussionsupporting

confidence: 93%

Rescue and evaluation of a recombinant PRRSV expressing porcine Interleukin-4

Wang

et al. 2015

Virol J

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“…The antibody response observed by ELISA is not protective and a fraction of these immunoglobulins have been associated with an immunopotentiating effect of PRRSV infection ( 53 ). The inhibition of antiviral cytokine responses through ligation of porcine FC gamma receptor I in pulmonary macrophages may account for the observed adverse effects ( 54 ), which could be also correlated with anti-idiotypic antibody responses ( 55 ). A few reports are available about the mucosal antibody response to PRRSV, which has been somewhat neglected by the scientific community.…”

Section: Mechanisms Of Immune Protection and Virus Clearancementioning

confidence: 99%

Immune Control of PRRS: Lessons to be Learned and Possible Ways Forward

Amadori¹,

Razzuoli²

2014

Front. Vet. Sci.

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Porcine reproductive and respiratory syndrome (PRRS) is an elusive model of host/virus relationship in which disease is determined by virus pathogenicity, pig breed susceptibility and phenotype, microbial infectious pressure, and environmental conditions. The disease can be controlled by farm management programs, which can be supported by vaccination or conditioning of animals to circulating PRRS virus (PRRSV) strains. Yet, PRRS still represents a cause of heavy losses for the pig industry worldwide. Immunological control strategies are often compounded by poor and late development of adaptive immunity in both vaccinated and infected animals. Also, there is evidence that results of field trials can be worse than those of experimental studies in isolation facilities. Neutralizing antibody (NA) was shown to prevent PRRSV infection. Instead, the role of NA and adaptive immunity on the whole in virus clearance after established PRRSV infections is still contentious. Pigs eventually eliminate PRRSV infection, which may be correlated with an “educated,” innate immune response, which may also develop following vaccination. In addition to vaccination, an immunomodulation strategy for PRRS can be reasonably advocated in pig “problem” farms, where a substantial control of disease prevalence and disease-related losses is badly needed. This is not at odds with vaccination, which should be preferably restricted to PRRSV-free animals bound for PRRSV-infected farm units. Oral, low-dose, interferon-α treatments proved effective on farm for the control of respiratory and reproductive disease outbreaks, whereas the results were less clear in isolation facilities. Having in mind the crucial interaction between PRRSV and bacterial lipopolysaccharides for occurrence of respiratory disease, the strong control actions of low-dose type I interferons on the inflammatory response observed in vitro and in vivo probably underlie the rapid clinical responses observed in field trials.

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“…A fifth possibility could be that the host mounts an auto-anti-idiotypic anti-receptor response against the complementary determining regions of antiviral Abs. [36][37][38] Finally, B-cell hyperplasia could also lead to production of anti-receptor Abs. 30,39 However, the presence of anti-receptor Abs in the early phase of HCV infection cannot be explained by B-cell hyperplasia given that the latter is associated with chronic HCV and hence the late phase of infection.…”

Section: Discussionmentioning

confidence: 99%

“…Fourth, it is conceivable that the profound neutralizing Ab response that is mounted during the acute phase of HCV infection could breach immune tolerance, leading to production of anti‐receptor Abs—a bystander effect, more likely in patients that resolve infection. A fifth possibility could be that the host mounts an auto–anti‐idiotypic anti‐receptor response against the complementary determining regions of anti‐viral Abs . Finally, B‐cell hyperplasia could also lead to production of anti‐receptor Abs .…”

Section: Discussionmentioning

confidence: 99%

Acute hepatitis C virus infection induces anti‐host cell receptor antibodies with virus‐neutralizing properties

et al. 2015

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Hepatitis C virus (HCV) causes persistent infection in the majority of infected individuals. The mechanisms of persistence and clearance are only partially understood. Antibodies (Abs) against host cell entry receptors have been shown to inhibit HCV infection in cell culture and animal models. In this study, we aimed to investigate whether anti-receptor Abs are induced during infection in humans in vivo and whether their presence is associated with outcome of infection. We established an enzyme-linked immunosorbant assay using a recombinant CD81-claudin-1 (CLDN1) fusion protein to detect and quantify Abs directed against extracellular epitopes of the HCV CD81-CLDN1 coreceptor complex. The presence of anti-receptor Abs was studied in serum of patients from a well-defined cohort of a single-source HCV outbreak of pregnant women and several control groups, including uninfected pregnant women, patients with chronic hepatitis B and D virus (HBV/HDV) infection, and healthy individuals. Virus-neutralizing activity of Abs was determined using recombinant cell culture-derived HCV (HCVcc). Our results demonstrate that HCVinfected patients have statistically significantly higher anti-CD81/CLDN1 Ab titers during the early phase of infection than controls. The titers were significantly higher in resolvers compared to persisters. Functional studies using immunoadsorption and HCV cell culture models demonstrate that HCV-neutralizing anti-receptor Abs are induced in the early phase of HCV infection, but not in control groups. Conclusion: The virus-neutralizing properties of these Abs suggest a role for control of viral infection in conjunction with antiviral responses. Characterization of these anti-receptor Abs opens new avenues to prevent and treat HCV infection. (HEPATOLOGY 2015;62:726-736) N early 170 million people are infected with hepatitis C virus (HCV) worldwide. 1 Approximately 85% of infected individuals develop persistent viral infection with a risk of developing liver cirrhosis and hepatocellular carcinoma; the remaining 15% clear the virus spontaneously. 2 Despite intensive efforts to understand the immune correlates of HCV clearance, the underlying mechanisms are still only

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Anti-idiotypic antibodies reduce efficacy of the attenuated vaccine against highly pathogenic PRRSV challenge

Cited by 10 publications

References 42 publications

Rescue and evaluation of a recombinant PRRSV expressing porcine Interleukin-4

Rescue and evaluation of a recombinant PRRSV expressing porcine Interleukin-4

Immune Control of PRRS: Lessons to be Learned and Possible Ways Forward

Acute hepatitis C virus infection induces anti‐host cell receptor antibodies with virus‐neutralizing properties

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