Commercial E2 subunit vaccine provides full protection to pigs against lethal challenge with 4 strains of classical swine fever virus genotype 2

Gong, Wenjie; Li, Junhui; Zunbao, Wang; Sun, Jixiang; Mi, Shijiang; Xu, Jialun; Cao, Jintao; Hou, Yuzhen; Wang, Danyang; Huo, Xinliang; Sun, Yanjun; Wang, Pengjiang; Yuan, Ke; Gao, Yangyi; Zhou, Xubin; Sun, He; Tu, Changchun

doi:10.1016/j.vetmic.2019.108403

Cited by 25 publications

(19 citation statements)

References 45 publications

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“…The vaccine was licensed in South Korea in 2017 and can be applied in domestic pigs as well as in wild boar [ 12 ]. In China, an inactivated vaccine based on a recombinant baculovirus expressing the CSFV E2 protein has been licensed in 2017 and is used by some pig farms [ 13 ]. No information is available whether the E2 subunit vaccine application is accompanied by DIVA testing.…”

Section: Introductionmentioning

confidence: 99%

Genetically distinct pestiviruses pave the way to improved classical swine fever marker vaccine candidates based on the chimeric pestivirus concept

Postel

Becher

2020

Emerging Microbes & Infections

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Classical swine fever (CSF) is one of the most important viral diseases of pigs. In many countries, the use of vaccines is restricted due to limitations of subunit vaccines with regard to efficacy and onset of protection as well as failure of live vaccines to d ifferentiate i nfected from v accinated a nimals (DIVA principle). Chimeric pestiviruses based on CSF virus (CSFV) and the related bovine viral diarrhea virus (BVDV) have been licensed as live marker vaccines in Europe and Asia, but cross-reactive antibodies can cause problems in DIVA application due to close antigenic relationship. To develop marker vaccine candidates with improved DIVA properties, three chimeric viruses were generated by replacing E rns of CSFV Alfort-Tübingen with homologue proteins of only distantly related pestiviruses. The chimeric viruses “Ra”, “Pro”, and “RaPro” contained E rns sequences of Norway rat and Pronghorn pestiviruses or a combination of both, respectively. In porcine cells, the “Pro” chimera replicated to high titers, while replication of the “Ra” chimera was limited. The “RaPro” chimera showed an intermediate phenotype. All vaccine candidates were attenuated in a vaccination/ challenge trial in pigs, but to different extents. Inoculation induced moderate to high levels of neutralizing antibodies that protected against infection with a genetically heterologous, highly virulent CSFV. Importantly, serum samples of vaccinated animals did not show any cross-reactivity in a CSFV E rns antibody ELISA. In conclusion, the E rns antigen from distantly related pestiviruses can provide a robust serological negative marker for a new generation of improved CSFV marker vaccines based on the chimeric pestivirus concept.

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Section: Introductionmentioning

confidence: 99%

Genetically distinct pestiviruses pave the way to improved classical swine fever marker vaccine candidates based on the chimeric pestivirus concept

Postel

Becher

2020

Emerging Microbes & Infections

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“…The group of 5 μg-E2ZJ developed sufficient CSFV specific antibodies at 21 dpi and neutralizing antibody at 7 dpi. Previous studies indicated that CSFV specific antibody response from single dose of 32 μg of E2 last for 6 to 13 month after immunization in pigs [21,44]. In this study, the immunogenic durability of single dose of 5 μg of E2ZJ in pigs was evaluated until 28 dpi, and the protective durability was monitored until 44 dpi (16 dpc, days post challenge).…”

Section: Discussionmentioning

confidence: 98%

“…E2 subunit vaccines have been confirmed to induce sufficient CSFV specific antibodies and provide complete protection against homologous CSFV in rabbits [18] and pigs [19,20]. Commercial CSFV E2 subunit vaccine Porcilis® Pesti derived from genotype 1 fail to elicit complete protection against heterologous strains of genotype 2.1 [18], while by booster immunization another commercial vaccine TWJ-E2® (genotype 1) was reported to provide complete protection against heterologous strains of genotype 2 [21]. However, these subunit vaccines usually require large multiple doses to induce the comparable CSFV-specific protective immunity as C-strain LAVs [22].…”

Section: Introductionmentioning

confidence: 99%

Identification of E2 with improved secretion and immunogenicity against CSFV in piglets

Wang

Han

et al. 2020

BMC Microbiol

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Background: Outbreaks of Classical swine fever virus (CSFV) cause significant economic losses in the swine industry. Vaccination is the major method to prevent and control the disease. As live attenuated vaccines fail to elicit differentiable immunity between infected and vaccinated animals, subunit vaccine was considered as an alternative candidate to prevent and eradicate CSFV. Subunit vaccines present advantages in DIVA immunogenicity and safety. The technology was limited due to the low yield and the high cost with multiple and large doses. The native E2 signal peptide has not been well defined before. Here, the aim of this study is to develop a cost-effective and efficacious E2 vaccine candidate against CSFV with signal peptide and E2 sequence selection. Results: A novel CSFV E2 sequence (E2ZJ) was identified from an epidemic strain of Zhejiang for outstanding secretion in baculovirus and enhanced immunogenicity. E2 secretion induced with the selected signal peptide, SPZJ (SP23), increase at least 50% as compared to any other signal peptides tested. Besides, unique antigenic features were identified in E2ZJ. As indicated with immunized sera in IFA against CSFV infection, E2ZJ elicited CSFV antibodies at the earlier stage than other E2 types tested in mice. Moreover, higher level of neutralizing and CSFV antibodies against CSFV with E2ZJ was detected than other E2s with the same dosage at 28 dpi. Further, E2ZJ successfully elicited neutralizing immunity in piglets. A single dose of 5 μg of E2ZJ was sufficient to induce protective antibodies against CSFV in piglets and provided 100% protection against lethal virus challenge. Conclusions: Our studies provide evidence that E2ZJ guided by a novel E2 signal peptide (SPZJ) was efficiently secreted and presented significantly improved immunogenicity than conventional E2 vaccines. Moreover, a single dose of 5 μg E2ZJ is efficacious against CSFV in piglets.

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“…The e cacy of different CSF-E2 subunit protein-based non-infectious marker vaccines has been demonstrated in previous studies [27,29,47,48]. However, incomplete e cacy of a previously authorized subunit marker vaccine (Porcilis® Pesti, Intervet International B.V.) resulting in vertical transmission in a contact-infection gilt experiment has been reported [48].…”

Section: Discussionmentioning

confidence: 98%

Evaluation of classical swine fever E2 (CSF-E2) subunit vaccine efficacy in the prevention of virus transmission and its potential application for virus eradication in field farms

Chen

et al. 2020

Preprint

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Background: Classical swine fever (CSF) is one of the most devastating pig diseases that affect the swine industry worldwide. Besides stamping out policy for eradication, immunization with vaccines of live attenuated CSF or the CSF-E2 subunit is an efficacious measure of disease control. However, after decades of efforts, it is still hard to eliminate CSF from endemically affected regions and reemerging areas. Most of previous studies demonstrated the efficacy of different CSF vaccines in laboratories under high containment conditions, which may not represent the practical performance in field farms. The inadequate vaccine efficacy induced by unrestrained factors may lead to chronic or persistent CSF infection in animals that develop a major source for virus shedding among pig populations. In this study, a vaccination-challenge-cohabitation trial on specific-pathogen-free (SPF) pigs and long-term monitoring of sows and piglets were used to evaluate the efficacy and the impact of maternally derived antibody (MDA) interference on CSF vaccines in farm applications.Results: The trials demonstrated higher neutralizing antibody (NA) titers with no clinical symptoms and significant pathological changes in the CSF-E2 subunit vaccine immunized group after CSFV challenge. Additionally, none of the sentinel pigs were infected during cohabitation indicating that the CSF-E2 subunit vaccine could provoke adequate acquired immunity to prevent horizontal transmission. In field farm applications, the CSF-E2 subunit vaccine significantly reduced CSF viral RNA detection via saliva monitoring in a sow population that was routinely immunized with live attenuated CSF vaccine long term. Moreover, no adverse effects and an average of higher, long-lasting and consistent NA level could be detected in sows immunized with CSF-E2 subunit vaccine before parturition. Furthermore, early application of the CSF-E2 subunit vaccine in 3-week-old piglets illustrated no MDA interference on primary immunization whereas interference of MDA was noted in piglets vaccinated with live attenuated CSF.Conclusions: The CSF-E2 subunit vaccine demonstrated more flexibility and efficacy for immunization in both pregnant sows and piglets. These advantages could provide a novel approach to avoid possible virus shedding in sow population and MDA interference in piglets for control of CSF in field farm applications.

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Commercial E2 subunit vaccine provides full protection to pigs against lethal challenge with 4 strains of classical swine fever virus genotype 2

Cited by 25 publications

References 45 publications

Genetically distinct pestiviruses pave the way to improved classical swine fever marker vaccine candidates based on the chimeric pestivirus concept

Genetically distinct pestiviruses pave the way to improved classical swine fever marker vaccine candidates based on the chimeric pestivirus concept

Identification of E2 with improved secretion and immunogenicity against CSFV in piglets

Evaluation of classical swine fever E2 (CSF-E2) subunit vaccine efficacy in the prevention of virus transmission and its potential application for virus eradication in field farms

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