Efficacy evaluation of the C-strain-based vaccines against the subgenotype 2.1d classical swine fever virus emerging in China

Luo, Yuzi; Ji, Shengwei; Lei, Jianlin; Xiang, Guang-Tao; Liu, Yan; Gao, Yao; Meng, Xuanyu; Zheng, Guanglai; Zhang, Enyu; Wang, Yimin; Du, Min; Li, Yongfeng; Su, Li; He, Xijun; Sun, Yuan; Qiu, Hua‐Ji

doi:10.1016/j.vetmic.2017.01.012

Cited by 32 publications

(25 citation statements)

References 18 publications

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“…Despite vaccine control strategies using the C-strain, a vaccine developed by serial passage in rabbits that led to its attenuation and that has been used as an effective vaccine against CSFV, the disease has continued to be endemic in several countries. Recently, in China, the emergence of subgenotype 2.1d occurred, causing mild pathological and histological lesions in C-strain vaccinated swine, suggesting that although no clinical symptoms are observed, the C-strain would not provide pathological and virological protection against the emerging subgenotypes [3]. A similar occurrence has also been observed in Cuba, where selective pressure has resulted in escape mutants from vaccination with the C-strain.…”

Section: Introductionmentioning

confidence: 73%

“…It is clear from these experiments that E2 residue substitutions that disrupt E2-SERTAD1 interactions in yeast two-hybrid appears to affect the ability of CSFV to replicate in cell cultures, particularly in primary swine macrophages. 104.16 (0.47) 3 1 All animals were IN inoculated with 10 5 TCID50 of the indicated virus. Animals were observed for 21 days after inoculation.…”

Section: Evaluation Of E2∆sertad1v In Virulence In Swinementioning

confidence: 99%

“…There are four structural proteins in CSFV, the core protein and three envelope glycoproteins, E rns , E1 and E2, which compose the CSFV particle. Mutations in the structure proteins have been linked to CSFV being able to escape vaccination strategies [3,4]. Understanding the molecular functions of these proteins, in particular, of specific residues that are involved in the processes of virus replication and virulence, has begun to be studied in the last few years [5][6][7][8][9][10][11] but is limited to only a few reports involving specific residues of these proteins.…”

Section: Introductionmentioning

confidence: 99%

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SERTA Domain Containing Protein 1 (SERTAD1) Interacts with Classical Swine Fever Virus Structural Glycoprotein E2, Which Is Involved in Virus Virulence in Swine

Vuono

Ramírez-Medina

Azzinaro

et al. 2020

Viruses

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E2 is the major structural glycoprotein of the classical swine fever virus (CSFV). E2 has been shown to be involved in important virus functions such as replication and virulence in swine. Using the yeast two-hybrid system, we previously identified several host proteins specifically interacting with CSFV E2. Here, we analyze the protein interaction of E2 with SERTA domain containing protein 1 (SERTAD1), a factor involved in the stimulation of the transcriptional activities of different host genes. We have confirmed that the interaction between these two proteins occurs in CSFV-infected swine cells by using a proximity ligation assay and confocal microscopy. Amino acid residues in the CSFV E2 protein that are responsible for mediating the interaction with SERTAD1 were mapped by a yeast two-hybrid approach using a randomly mutated E2 library. Using that information, a recombinant CSFV mutant (E2ΔSERTAD1v) that harbors substitutions in those residues mediating the protein-interaction with SERTAD1 was developed and used to study the role of the E2-SERTAD1 interaction in viral replication and virulence in swine. CSFV E2ΔSERTAD1v, when compared to the parental BICv, showed a clearly decreased ability to replicate in the SK6 swine cell line and a more severe replication defect in primary swine macrophage cultures. Importantly, 80% of animals infected with E2ΔSERTAD1v survived infection, remaining clinically normal during the 21-day observational period. This result would indicate that the ability of CSFV E2 to bind host SERTAD1 protein during infection plays a critical role in virus virulence.

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Section: Introductionmentioning

confidence: 73%

Section: Evaluation Of E2∆sertad1v In Virulence In Swinementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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SERTA Domain Containing Protein 1 (SERTAD1) Interacts with Classical Swine Fever Virus Structural Glycoprotein E2, Which Is Involved in Virus Virulence in Swine

Vuono

Ramírez-Medina

Azzinaro

et al. 2020

Viruses

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“…Nevertheless, development of new subunit vaccines remains a major area of research with the goal of fulfilling the following: early onset of protection with sterile immunity, long‐lasting immunity (the animal life cycle in the pork industry is about 7–8 months), safety without viral shedding among animals and low‐cost production. Importantly, subunit vaccines provide alternatives to protect pig populations against emerging subgenotypes for which current live attenuated CSFV vaccines are not highly protective, such as the emerging subgenotype 2.1d recently reported in India (Gong et al ., ) and south‐east Asia (Luo et al ., ).…”

Section: Discussionmentioning

confidence: 97%

Plant‐made E2 glycoprotein single‐dose vaccine protects pigs against classical swine fever

Laughlin

Madera

Peres³

et al. 2018

Plant Biotechnology Journal

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Classical Swine Fever Virus (CSFV) causes classical swine fever, a highly contagious hemorrhagic fever affecting both feral and domesticated pigs. Outbreaks of CSF in Europe, Asia, Africa and South America had significant adverse impacts on animal health, food security and the pig industry. The disease is generally contained by prevention of exposure through import restrictions (e.g. banning import of live pigs and pork products), localized vaccination programmes and culling of infected or at-risk animals, often at very high cost. Current CSFV-modified live virus vaccines are protective, but do not allow differentiation of infected from vaccinated animals (DIVA), a critical aspect of disease surveillance programmes. Alternatively, first-generation subunit vaccines using the viral protein E2 allow for use of DIVA diagnostic tests, but are slow to induce a protective response, provide limited prevention of vertical transmission and may fail to block viral shedding. CSFV E2 subunit vaccines from a baculovirus/insect cell system have been developed for several vaccination campaigns in Europe and Asia. However, this expression system is considered expensive for a veterinary vaccine and is not ideal for wide-spread deployment. To address the issues of scalability, cost of production and immunogenicity, we have employed an Agrobacterium-mediated transient expression platform in Nicotiana benthamiana and formulated the purified antigen in novel oil-in-water emulsion adjuvants. We report the manufacturing of adjuvanted, plant-made CSFV E2 subunit vaccine. The vaccine provided complete protection in challenged pigs, even after single-dose vaccination, which was accompanied by strong virus neutralization antibody responses.

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“…According to many experimental challenge studies (Blome et al., ; Graham et al., ; Luo et al., ; Suradhat & Damrongwatanapokin, ), it is considered that vaccination drastically reduces clinical manifestations, irrespective of the genotype of the challenge strains. However, in contrast to that observed with genotype 1, prolonged viremia was common in vaccinated pigs infected with genotype 2 CSFV strains (Blome et al., ; Luo et al., ); furthermore, faecal shedding and histopathological lesions were identified in pigs challenged with a Chinese EEN strain, although clinical signs of infection were absent. A positive correlation between transmission risk and the genetic distance between previous immunization viruses and the challenge virus has been demonstrated for the influenza virus (Park et al., ).…”

Section: Discussionmentioning

confidence: 99%

Genetic evolution of classical swine fever virus under immune environments conditioned by genotype 1-based modified live virus vaccine

Yoo

Kwon

Kang³

et al. 2018

Transbound Emerg Dis

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Modified live vaccines (MLVs) based on genotype 1 strains, particularly C-strain, have been used to prevent and control classical swine fever virus (CSFV) worldwide. Nevertheless, a shift in the predominant CSFV strains circulating in the field from genotype 1 or 3 to genotype 2 is seen. Genotype 2 is genetically distant from the vaccine strains and was recently reported during outbreaks after vaccine failure; this has raised concerns that vaccination has influenced viral evolution. In Korea in 2016, there was an unexpected CSF outbreak in a MLV-vaccinated commercial pig herd. The causative CSFV strain was genetically distinct from previously isolated Korean strains but similar to recent Chinese strains exhibiting enhanced capacity to escape neutralization; this suggests the need for global cooperative research on the evolution of CSFV. We analysed global E2 sequences, using bioinformatics tools, revealing the evolutionary pathways of CSFV. Classical swine fever virus genotypes 1 and 2 experienced different degrees and patterns of evolutionary growth. Whereas genotype 1 stayed relatively conserved over time, the genetic diversity of genotype 2 has progressively expanded, with few fluctuations. It was determined that genotype 2 evolved under lower immune pressures and at a higher evolutionary rate than genotype 1. Further, several selected codons, under diversifying selection in genotype 1 but under purifying selection in genotype 2, correspond to antigenic determinants, which could lead to evasion of vaccine-induced immunity. Our findings provide evidence that evolutionary changes in CSFV are the result of the disproportionate usage of the CSF MLVs in endemic areas; this underscores the need to develop mitigation strategies to minimize the substantial risk associated with the emergence of vaccine-escaping mutants.

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Efficacy evaluation of the C-strain-based vaccines against the subgenotype 2.1d classical swine fever virus emerging in China

Cited by 32 publications

References 18 publications

SERTA Domain Containing Protein 1 (SERTAD1) Interacts with Classical Swine Fever Virus Structural Glycoprotein E2, Which Is Involved in Virus Virulence in Swine

SERTA Domain Containing Protein 1 (SERTAD1) Interacts with Classical Swine Fever Virus Structural Glycoprotein E2, Which Is Involved in Virus Virulence in Swine

Plant‐made E2 glycoprotein single‐dose vaccine protects pigs against classical swine fever

Genetic evolution of classical swine fever virus under immune environments conditioned by genotype 1-based modified live virus vaccine

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