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Development and Application of New Vaccine against Classical Swine Fever Virus

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A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Veterinary Vaccines".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 34553

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Prof. Lester J. Perez

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Guest Editor

Veterinary Diagnostic Laboratory, College of Veterinary Medicine, University of Illinois, Urbana, IL 61802, USA
Interests: molecular epidemiology; virology; cell-virus interactions; molecular diagnostic; vaccine; bioinformatics; immunology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Classical swine fever (CSF) is considered one of the most important infectious diseases in animal health. The disease is caused by CSF virus (CSFV), a Pestivirus member and is highly contagious affecting both domestic pigs and wild boar. Despite the implemented efforts by many government authorities to control and eradicate CSF from national pig populations, the disease remains as a significant challenge evidenced by the current re-emergence of CSF in several countries including Brazil, Ecuador South Korea and Japan as well as the status of endemic that the virus kept in other geographic areas including China. Whereas the control of CSF has been mainly based on live modified vaccines or lapinized vaccines developed during the mid‐1950s, recent studies have evidenced the urgent needs of novel advances vaccines and strategies which enable to elicit robust humoral and cellular immunities avoiding the emergence of escaping variants.

This Special Issue will focus on the advances in the development of novel vaccines and strategies against CSFV, looking to gather the current knowledge in epitope characterization, rational design of vaccines and molecular characterization of escaping variants for this viral agent.

Prof. Lester J. Perez
Guest Editor

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Keywords

Classical swine fever virus
vaccine
epitope characterization
immune response
positive selection pressure
bottleneck effect
humoral immune response
cellular immune response

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Published Papers (9 papers)

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Research

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10 pages, 1930 KiB

Open AccessArticle

Assessing the Protective Dose of a Candidate DIVA Vaccine against Classical Swine Fever

by Tinka Jelsma, Jacob Post, Erwin van den Born, Ruud Segers and Jeroen Kortekaas

Vaccines 2021, 9(5), 483; https://doi.org/10.3390/vaccines9050483 - 10 May 2021

Cited by 6 | Viewed by 5467

Abstract

Classical swine fever is a highly contagious and deadly disease in swine. The disease can be controlled effectively by vaccination with an attenuated virus known as the “Chinese” (C)-strain. A single vaccination with the C-strain provides complete protection against highly virulent isolates within days after vaccination, making it one of the most efficacious veterinary vaccines ever developed. A disadvantage of the C-strain is that vaccinated animals cannot be serologically differentiated from animals that are infected with wild-type Classical swine fever virus. Previously, a C-strain-based vaccine with a stable deletion in the E2 structural glycoprotein was developed, which allows for differentiation between infected and vaccinated animals (DIVA). The resulting vaccine, which we named C-DIVA, is compatible with a commercial E2 ELISA, modified to render it suitable as a DIVA test. In the present work, three groups of eight piglets were vaccinated with escalating doses of the C-DIVA vaccine and challenged two weeks after vaccination. One group of four unvaccinated piglets served as controls. Piglets were monitored for clinical signs until three weeks after challenge and blood samples were collected to monitor viremia, leukocyte and thrombocyte levels, and antibody responses. The presence of challenge virus RNA in oropharyngeal swabs was investigated to first gain insight into the potential of C-DIVA to prevent shedding. The results demonstrate that a single vaccination with 70 infectious virus particles of C-DIVA protects pigs from the highly virulent Brescia strain. Full article

(This article belongs to the Special Issue Development and Application of New Vaccine against Classical Swine Fever Virus)

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14 pages, 3247 KiB

Open AccessArticle

Early and Solid Protection Afforded by the Thiverval Vaccine Provides Novel Vaccination Alternatives Against Classical Swine Fever Virus

by Yaneysis Lamothe-Reyes, José Alejandro Bohórquez, Miaomiao Wang, Mònica Alberch, Marta Pérez-Simó, Rosa Rosell and Llilianne Ganges

Vaccines 2021, 9(5), 464; https://doi.org/10.3390/vaccines9050464 - 6 May 2021

Cited by 6 | Viewed by 3168

Abstract

Classical swine fever virus (CSFV) remains a challenge for the porcine industry. Inefficient vaccination programs in some endemic areas may have contributed to the emergence of low and moderate virulence CSFV variants. This work aimed to expand and update the information about the safety and efficacy of the CSFV Thiverval-strain vaccine. Two groups of pigs were vaccinated, and a contact and control groups were also included. Animals were challenged with a highly virulent CSFV strain at 21- or 5-days post vaccination (dpv). The vaccine induced rapid and strong IFN-α response, mainly in the 5-day immunized group, and no vaccine virus transmission was detected. Vaccinated pigs showed humoral response against CSFV E2 and E^rns glycoproteins, with neutralising activity, starting at 14 days post vaccination (dpv). Strong clinical protection was afforded in all the vaccinated pigs as early as 5 dpv. The vaccine controlled viral replication after challenge, showing efficient virological protection in the 21-day immunized pigs despite being housed with animals excreting high CSFV titres. These results demonstrate the high efficacy of the Thiverval strain against CSFV replication. Its early protection capacity makes it a useful alternative for emergency vaccination and a consistent tool for CSFV control worldwide. Full article

(This article belongs to the Special Issue Development and Application of New Vaccine against Classical Swine Fever Virus)

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11 pages, 1051 KiB

Open AccessArticle

A Novel E2 Glycoprotein Subunit Marker Vaccine Produced in Plant Is Able to Prevent Classical Swine Fever Virus Vertical Transmission after Double Vaccination

by Youngmin Park, Yeonsu Oh, Miaomiao Wang, Llilianne Ganges, José Alejandro Bohórquez, Soohong Park, Sungmin Gu, Jungae Park, Sangmin Lee, Jongkook Kim and Eun-Ju Sohn

Vaccines 2021, 9(5), 418; https://doi.org/10.3390/vaccines9050418 - 22 Apr 2021

Cited by 10 | Viewed by 2714

Abstract

The efficacy of a novel subunit vaccine candidate, based in the CSFV E2 glycoprotein produced in plants to prevent classical swine fever virus (CSFV) vertical transmission, was evaluated. A Nicotiana benthamiana tissue culture system was used to obtain a stable production of the E2-glycoprotein fused to the porcine Fc region of IgG. Ten pregnant sows were divided into three groups: Groups 1 and 2 (four sows each) were vaccinated with either 100 μg/dose or 300 μg/dose of the subunit vaccine at 64 days of pregnancy. Group 3 (two sows) was injected with PBS. Groups 1 and 2 were boosted with the same vaccine dose. At 10 days post second vaccination, the sows in Groups 2 and 3 were challenged with a highly virulent CSFV strain. The vaccinated sows remained clinically healthy and seroconverted rapidly, showing efficient neutralizing antibodies. The fetuses from vaccinated sows did not show gross lesions, and all analyzed tissue samples tested negative for CSFV replication. However, fetuses of non-vaccinated sows had high CSFV replication in tested tissue samples. The results suggested that in vaccinated sows, the plant produced E2 marker vaccine induced the protective immunogenicity at challenge, leading to protection from vertical transmission to fetuses. Full article

(This article belongs to the Special Issue Development and Application of New Vaccine against Classical Swine Fever Virus)

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11 pages, 2485 KiB

Open AccessArticle

Comparative Analysis of the Productivity and Immunogenicity of an Attenuated Classical Swine Fever Vaccine (LOM) and an Attenuated Live Marker Classical Swine Fever Vaccine (Flc-LOM-BE^rns) from Laboratory to Pig Farm

by SeEun Choe, Ki-Sun Kim, Jihye Shin, Sok Song, Gyu-Nam Park, Ra Mi Cha, Sung-Hyun Choi, Byung-Il Jung, Kyung-Won Lee, Bang-Hun Hyun, Bong-Kyun Park and Dong-Jun An

Vaccines 2021, 9(4), 381; https://doi.org/10.3390/vaccines9040381 - 13 Apr 2021

Cited by 3 | Viewed by 2996

Abstract

Herein, we compared the productivity of pigs inoculated with one of two classical swine fever (CSF) vaccines (low virulent of Miyagi (LOM) or Flc-LOM-BE^rns) plus the swine erysipelothrix rhusiopathiae (SE) vaccine. The feed intake and weight increase of the pigs inoculated with Flc-LOM-BE^rns + SE were normal. However, the feed intake of the pigs inoculated with LOM + SE dropped sharply from four days post-vaccination (dpv). In addition, the slaughter date was an average of eight days later than that of the pigs inoculated with Flc-LOM-BE^rns + SE. All pigs inoculated with the Flc-LOM-BE^rns + SE vaccine were completely differentiated at 14 days against CSF E^rns antibody and at approximately 45 days against the bovine viral diarrhea virus (BVDV) E^rns antibody; the titers were maintained until slaughter. Leucopenia occurred temporarily in the LOM + SE group, but not in the Flc-LOM-BE^rns + SE group. Expression of tumor necrosis factor (TNF)-α and IFN-γ was significantly (p < 0.05) higher in the LOM + SE group than in the mock (no vaccine) group. When conducting the same experiment on a breeding farm, the results were similar to those of the laboratory experiments. In conclusion, the biggest advantage of replacing the CSF LOM vaccine with the Flc-LOM-BE^rns vaccine is improved productivity. Full article

(This article belongs to the Special Issue Development and Application of New Vaccine against Classical Swine Fever Virus)

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11 pages, 1624 KiB

Open AccessArticle

Porvac^® Subunit Vaccine E2-CD154 Induces Remarkable Rapid Protection against Classical Swine Fever Virus

by Yusmel Sordo-Puga, Marisela Suárez-Pedroso, Paula Naranjo-Valdéz, Danny Pérez-Pérez, Elaine Santana-Rodríguez, Talia Sardinas-Gonzalez, Mary Karla Mendez-Orta, Carlos A. Duarte-Cano, Mario Pablo Estrada-Garcia and María Pilar Rodríguez-Moltó

Vaccines 2021, 9(2), 167; https://doi.org/10.3390/vaccines9020167 - 17 Feb 2021

Cited by 10 | Viewed by 4122

Abstract

Live attenuated C-strain classical swine fever vaccines provide early onset protection. These vaccines confer effective protection against the disease at 5–7 days post-vaccination. It was previously reported that intramuscular administration of the Porvac^® vaccine protects against highly virulent classical swine fever virus (CSFV) “Margarita” strain as early as seven days post-vaccination. In order to identify how rapidly protection against CSFV is conferred after a single dose of the Porvac^® subunit vaccine E2-CD154, 15 swine, vaccinated with a single dose of Porvac^®, were challenged intranasally at five, three, and one day post-vaccination with 2 × 10³ LD₅₀ of the highly pathogenic Cuban “Margarita” strain of the classical swine fever virus. Another five animals were the negative control of the experiment. The results provided clinical and virological data confirming protection at five days post-vaccination. Classical swine fever (CSF)-specific IFNγ T cell responses were detected in vaccinated animals but not detected in unvaccinated control animals. These results provided the first data that a subunit protein vaccine demonstrates clinical and viral protection at five days post-vaccination, as modified live vaccines. Full article

(This article belongs to the Special Issue Development and Application of New Vaccine against Classical Swine Fever Virus)

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14 pages, 4737 KiB

Open AccessArticle

A Self-Assembling Ferritin Nanoplatform for Designing Classical Swine Fever Vaccine: Elicitation of Potent Neutralizing Antibody

by Zekai Zhao, Xinghua Chen, Yibao Chen, Hui Li, Kui Fang, Huanchun Chen, Xiangmin Li and Ping Qian

Vaccines 2021, 9(1), 45; https://doi.org/10.3390/vaccines9010045 - 13 Jan 2021

Cited by 17 | Viewed by 3424

Abstract

Protein-based self-assembling nanoplatforms exhibit superior immunogenicity compared with soluble antigens. Here, we present a comprehensive vaccine strategy for displaying classical swine fever virus (CSFV) E2 glycoprotein on the surface of ferritin (fe) nanocages. An E2-specific blocking antibody assay showed that the blocking rates in pE2-fe/Gel02 (84.3%) and a half-dose cohort of E2-fe/Gel02 (81.9%) were significantly higher (p < 0.05) than that in a ferritin-free cohort of pE2/Gel02 (62.7%) at 21 days post immunization (dpi) in vivo. Furthermore, quantitation of neutralizing potency revealed that a highly significant difference (p < 0.001) was observed between the pE2-fe/Gel02 cohort (1:32, equivalent to live-attenuated strain C at 1:32) and the pE2/Gel02 cohort (1:4) at 21 dpi. Moreover, the innate immune cytokines of IL-4 and IFN-γ activated by the half-dose (20 μg) cohort of E2-fe/Gel02 were equivalent to those elicited by the full dose (40 μg) of purified E2 in the pE2/Gel02 cohort at most time points. In conclusion, we successfully obtained an antigen-displaying E2-ferritin nanoplatform and confirmed high ferritin-assisted humoral and cellular immunities. Our results provided a novel paradigm of self-assembling nanovaccine development for the defense and elimination of potentially pandemic infectious viral pathogens. Full article

(This article belongs to the Special Issue Development and Application of New Vaccine against Classical Swine Fever Virus)

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9 pages, 1681 KiB

Open AccessArticle

Immunogenicity of E2CD154 Subunit Vaccine Candidate against Classical Swine Fever in Piglets with Different Levels of Maternally Derived Antibodies

by Yusmel Sordo-Puga, Danny Pérez-Pérez, Carlos Montero-Espinosa, Aymé Oliva-Cárdenas, Iliana Sosa-Teste, Carlos A. Duarte, María Pilar Rodríguez-Moltó, Talía Sardina-González, Elaine Santana-Rodríguez, Milagros Vargas-Hernández, Yaneris Cabrera-Otaño, Julio A. Ancizar-Fragoso, Yohandy Fuentes-Rodríguez, Mario Pablo Estrada and Marisela Suárez-Pedroso

Vaccines 2021, 9(1), 7; https://doi.org/10.3390/vaccines9010007 - 24 Dec 2020

Cited by 7 | Viewed by 2804

Abstract

E2CD154 is a novel subunit vaccine candidate against classical swine fever virus (CSFV). It contains the E2 envelope protein from CSFV fused to the porcine CD154 molecule formulated in the oil adjuvant Montanide^TM ISA50 V2. Previous works evidenced the safety and immunogenicity of this candidate. Here, two other important parameters related to vaccine efficacy were assessed. First, the existence of high maternally derived antibody (MDA) titers in piglets born to sows vaccinated with E2CD154 was demonstrated. These MDA titers remained above 1:200 during the first seven weeks of life. To assess whether the titers interfere with active vaccination, 79 piglets from sows immunized with either E2CD154 or a modified live vaccine were vaccinated with E2CD154 following a 0–21-day biphasic schedule. Animals immunized at either 15, 21, or 33 days of age responded to vaccination by eliciting protective neutralizing antibody (NAb) titers higher than 1:600, with a geometric mean of 1:4335, one week after the booster. Those protective levels of NAb were sustained up to six months of age. No vaccination-related adverse effects were described. As a conclusion, E2CD154 is able to induce protective NAb in piglets with different MDA levels and at different days of age. Full article

(This article belongs to the Special Issue Development and Application of New Vaccine against Classical Swine Fever Virus)

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Review

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32 pages, 540 KiB

Open AccessReview

A Critical Review about Different Vaccines against Classical Swine Fever Virus and Their Repercussions in Endemic Regions

by Liani Coronado, Carmen L. Perera, Liliam Rios, María T. Frías and Lester J. Pérez

Vaccines 2021, 9(2), 154; https://doi.org/10.3390/vaccines9020154 - 15 Feb 2021

Cited by 43 | Viewed by 5808

Abstract

Classical swine fever (CSF) is, without any doubt, one of the most devasting viral infectious diseases affecting the members of Suidae family, which causes a severe impact on the global economy. The reemergence of CSF virus (CSFV) in several countries in America, Asia, and sporadic outbreaks in Europe, sheds light about the serious concern that a potential global reemergence of this disease represents. The negative aspects related with the application of mass stamping out policies, including elevated costs and ethical issues, point out vaccination as the main control measure against future outbreaks. Hence, it is imperative for the scientific community to continue with the active investigations for more effective vaccines against CSFV. The current review pursues to gather all the available information about the vaccines in use or under developing stages against CSFV. From the perspective concerning the evolutionary viral process, this review also discusses the current problematic in CSF-endemic countries. Full article

(This article belongs to the Special Issue Development and Application of New Vaccine against Classical Swine Fever Virus)

Other

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10 pages, 1194 KiB

Open AccessCase Report

Field Application of a New CSF Vaccine Based on Plant-Produced Recombinant E2 Marker Proteins on Pigs in Areas with Two Different Control Strategies

by Yeonsu Oh, Youngmin Park, Bo-Hwa Choi, Soohong Park, Sungmin Gu, Jungae Park, Jong-Kook Kim and Eun-Ju Sohn

Vaccines 2021, 9(6), 537; https://doi.org/10.3390/vaccines9060537 - 21 May 2021

Cited by 8 | Viewed by 2504

Abstract

A classical swine fever virus (CSFV)-modified live LOM (low-virulence strain of Miyagi) vaccine (MLV-LOM) to combat CSF has been used in places where the disease is prevalent around the world, including in Korea, except in Jeju Island. In general, modified live virus-based vaccines (MLV) are known to be highly effective in inducing immune responses. At the same time, MLVs also have potential dangers such as a circulation in the field. There is still a need for safer and more effective vaccines to control CSF in the field. In this study, we applied a new CSF vaccine based on plant-produced recombinant E2 marker proteins at two different locations, Jeju Island and a suburb of Pohang, using different CSF control strategies. The result suggested that vaccinated sows in Jeju Island highly developed immunogenicity and maintained stably until 102 days post-vaccination (dpv). Its piglets that received maternal antibodies were shown to carry high serological values and maintained them until 40 days of age, which was the end of the follow-up. Naïve piglets vaccinated at 40 days of age showed high serological values and these were maintained until 100 days of age (60 dpv), which was the end of the follow-up. The vaccine was also effective in inducing immune responses in newborn piglets that carried maternal antibodies received from MLV-LOM vaccine-immunized mother sows. Full article

(This article belongs to the Special Issue Development and Application of New Vaccine against Classical Swine Fever Virus)

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