African swine fever virus vaccine candidate ASFV‐G‐DI177L efficiently protects European and native pig breeds against circulating Vietnamese field strain

African swine fever virus (ASFv) is one of the most challenging pathogens to affect both domestic and wild pigs. The disease has now spread to Europe and Asia, causing great damage to the pig industry. Although no commercial vaccine with which to control the disease is, as yet, available, some potential vaccine candidates have shown good results in terms of protection. However, little is known about the host immune mechanisms underlying that protection, especially in wild boar, which is the main reservoir of the disease in Europe. Here, we study the role played by two cytokines (IL-10 and IFN-γ) in wild boar orally inoculated with the attenuated vaccine candidate Lv17/WB/Rie1 and challenged with a virulent ASFv genotype II isolate. A group of naïve wild boar challenged with the latter isolate was also established as a control group. Our results showed that both cytokines play a key role in protecting the host against the challenge virus. While high levels of IL-10 in serum may trigger an immune system malfunctioning in challenged animals, the provision of stable levels of this cytokine over time may help to control the disease. This, together with high and timely induction of IFN-γ by the vaccine candidate, could help protect animals from fatal outcomes. Further studies should be conducted in order to support these preliminary results and confirm the role of these two cytokines as potential markers of the evolution of ASFV infection.

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Expression and purification of African Swine Fever virus p72 trimers as subunit vaccine candidate

10.1101/2020.01.30.926808 ◽

2020 ◽

Author(s):

Kaiwen Meng ◽

Yueping Zhang ◽

Wenzhuang Zhu ◽

Ye Xiang ◽

Geng Meng

Keyword(s):

Subunit Vaccine ◽

Vaccine Candidate ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Fever Virus ◽

Expression And Purification ◽

Technical Approach

The authors have withdrawn this manuscript because the result is invalid. We intend to revise it on our technical approach and interpretation of the results. The authors do not wish for this manuscript to be cited as a reference for this project. Please contact the corresponding author if you have any questions.

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Deletion of A137R gene from the pandemic strain of African swine fever virus is attenuated and offers protection against virulent pandemic virus

Journal of Virology ◽

10.1128/jvi.01139-21 ◽

2021 ◽

Author(s):

Douglas P. Gladue ◽

Elizabeth Ramirez-Medina ◽

Elizabeth Vuono ◽

Ediane Silva ◽

Ayushi Rai ◽

...

Keyword(s):

East Asia ◽

Central Europe ◽

Vaccine Candidate ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Fever Virus ◽

Economic Losses ◽

Live Attenuated Vaccine ◽

Attenuated Vaccine ◽

Highly Virulent

African swine fever virus (ASFV) is causing a devastating pandemic in domestic and wild swine within an extended geographical area from Central Europe to East Asia resulting in economic losses for the regional swine industry. There are no commercial vaccines, therefore disease control relies on identification and culling of infected animals. We report here that the deletion of the ASFV gene A137R from the highly virulent ASFV-Georgia2010 (ASFV-G) isolate induces a significant attenuation of virus virulence in swine. A recombinant virus lacking the A137R gene, ASFV-G-ΔA137R, was developed to assess the role of this gene in ASFV virulence in domestic swine. Animals inoculated intramuscularly with 10 2 HAD 50 of ASFV-G-ΔA137R remained clinically healthy during the 28 day observational period. All animals inoculated with ASFV-G-ΔA137R had medium to high viremia titers and developed a strong virus-specific antibody response. Importantly, all ASFV-G-ΔA137R-inoculated animals were protected when challenged with the virulent parental strain ASFV-G. No evidence of replication of challenge virus was observed in the ASFV-G-ΔA137R-inoculated animals. Therefore, ASFV-G-ΔA137R is a novel potential live attenuated vaccine candidate and one of the few experimental vaccine strains reported to induce protection against the highly virulent ASFV Georgia virus that is the cause of the current Eurasian pandemic. Importance: No commercial vaccine is available to prevent African swine fever. The ASF pandemic caused by ASFV Georgia2007 (ASFV-G) is seriously affecting pork production in a contiguous area from Central Europe to East Asia. Here we report the rational development of a potential live attenuated vaccine strain by deleting a virus-specific gene, A137R, from the genome of ASFV-G. The resulting virus presented a completely attenuated phenotype and, importantly, animals infected with this genetically modified virus were protected from developing ASF after challenge with the virulent parental virus. ASFV-G-ΔA137R confers protection even at low doses (10 2 HAD 50 ) demonstrating its potential as a vaccine candidate. Therefore, ASFV-G-ΔA137R is a novel experimental ASF vaccine protecting pigs from the epidemiologically relevant ASFV Georgia isolate.

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The recombinant pseudorabies virus expressing African swine fever virus CD2v protein is safe and effective in mice

Virology Journal ◽

10.1186/s12985-020-01450-7 ◽

2020 ◽

Vol 17 (1) ◽

Author(s):

Zhihua Feng ◽

Jianghua Chen ◽

Wangwang Liang ◽

Wenzhi Chen ◽

Zhaolong Li ◽

...

Keyword(s):

Recombinant Virus ◽

Recombinant Strain ◽

Pseudorabies Virus ◽

Vaccine Candidate ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Vero Cells ◽

Fever Virus ◽

Virus Vaccination ◽

Recombinant Pseudorabies Virus

Abstract Background African swine fever (ASF) leads to high mortality in domestic pigs and wild boar and is caused by the African swine fever virus (ASFV). Currently, no vaccine is commercially available for prevention, and the epidemic is still spreading. Here, we constructed a recombinant pseudorabies virus (PRV) (PRV-ΔgE/ΔgI/ΔTK-(CD2v)) that expresses the CD2v protein of ASFV and evaluated its effectiveness and safety as a vaccine candidate in mice. Methods A homologous recombination fragment containing ASFV CD2v was synthesized and co-transfected into HEK 293 T cells, a knockout vector targeting the PRV TK gene. The transfected cells were infected with PRV-ΔgE/ΔgI, and the recombinant strain (PRV-ΔgE/ΔgI/ΔTK-(CD2v)) was obtained by plaque purification in Vero cells. The expression of ASFV CD2v in the recombinant virus was confirmed by sequencing, Western blotting, and immunofluorescence analysis, and the genetic stability was tested in Vero cells over 20 passages. The virulence, immunogenicity and protective ability of the recombinant virus were further tested in a mouse model. Results The PRV-ΔgE/ΔgI/ΔTK-(CD2v) recombinant strain is stable in Vero cells, and the processing of CD2v does not depend on ASFV infection. The vaccination of PRV-ΔgE/ΔgI/ΔTK-(CD2v) causes neither pruritus, not a systemic infection and inflammation (with the high expression of interleukin-6 (IL6)). Besides, the virus vaccination can produce anti-CD2v specific antibody and activate a specific cellular immune response, and 100% protect mice from the challenge of the virulent strain (PRV-Fa). The detoxification occurs much earlier upon the recombinant virus vaccination and the amount of detoxification is much lower as well. Conclusions The PRV-ΔgE/ΔgI/ΔTK-(CD2v) recombinant strain has strong immunogenicity, is safe and effective, and maybe a potential vaccine candidate for the prevention of ASF and Pseudorabies.

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Modern adjuvants do not enhance the efficacy of an inactivated African swine fever virus vaccine preparation

Vaccine ◽

10.1016/j.vaccine.2014.05.051 ◽

2014 ◽

Vol 32 (31) ◽

pp. 3879-3882 ◽

Cited By ~ 35

Author(s):

Sandra Blome ◽

Claudia Gabriel ◽

Martin Beer

Keyword(s):

Virus Vaccine ◽

African Swine Fever Virus ◽

African Swine Fever ◽

Fever Virus ◽

Vaccine Preparation

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Development of a highly effective African swine fever virus vaccine by deletion of the I177L gene results in sterile immunity against the current epidemic Eurasia strain

10.1101/861666 ◽

2019 ◽

Cited By ~ 1

Author(s):

Manuel V. Borca ◽

Elizabeth Ramirez Medina ◽

Ediane Silva ◽

Elizabeth Vuono ◽

Ayushi Rai ◽

...

Keyword(s):

East Asia ◽

Central Europe ◽

Vaccine Candidate ◽

African Swine Fever Virus ◽

Dose Range ◽

African Swine Fever ◽

Fever Virus ◽

Swine Industry ◽

Virus Shedding ◽

Clinically Normal

AbstractAfrican swine fever virus (ASFV) is the etiological agent of a contagious and often lethal disease of domestic pigs that has significant economic consequences for the swine industry. The disease is devastating the swine industry in Central Europe and East Asia, with current outbreaks caused by circulating strains of ASFV derived from the 2007 Georgia isolate (ASFV-G), a genotype II ASFV. In the absence of any available vaccines, African Swine Fever (ASF) outbreak containment relies on control and culling of infected animals. Limited cross protection studies suggest that in order to ensure a vaccine is effective it must be derived from the current outbreak strain or at the very least from an isolate with the same genotype. Here we report the discovery that deletion of a previously uncharacterized gene, I177L, from the highly virulent ASFV-G produces complete virus attenuation in swine. Animals inoculated intramuscularly with the virus lacking the I177L gene, ASFV-G-ΔI177L, in a dose range of 102 to 106 HAD50 remained clinically normal during the 28 day observational period. All ASFV-G-ΔI177L-infected animals had low viremia titers, showed no virus shedding, developed a strong virus-specific antibody response and, importantly, they were protected when challenged with the virulent parental strain ASFV-G. ASFV-G-ΔI177L is one of the few experimental vaccine candidate virus strains reported to be able to induce protection against the ASFV Georgia isolate, and the first vaccine capable of inducing sterile immunity against the current ASFV strain responsible for recent outbreaks.ImportanceCurrently there is no commercially available vaccine against African swine fever. Outbreaks of this disease are devastating the swine industry from Central Europe to East Asia, and they are being caused by circulating strains of African swine fever virus derived from the Georgia2007 isolate. Here we report the discovery of a previously uncharacterized virus gene, which when deleted completely attenuates the Georgia isolate. Importantly, animals infected with this genetically modified virus were protected from developing ASF after challenge with the virulent parental virus. Interestingly, ASFV-G-ΔI177L confers protection even at low doses (102 HAD50) and remains completely attenuated when inoculated at high doses (106 HAD50), demonstrating its potential as a safe vaccine candidate. At medium doses (104 HAD50) sterile immunity is achieved. Therefore, ASFV-G-ΔI177L is a novel efficacious experimental ASF vaccine protecting pigs from the epidemiologically relevant ASFV Georgia isolate.

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Development of a Highly Effective African Swine Fever Virus Vaccine by Deletion of the I177L Gene Results in Sterile Immunity against the Current Epidemic Eurasia Strain

Journal of Virology ◽

10.1128/jvi.02017-19 ◽

2020 ◽

Vol 94 (7) ◽

Cited By ~ 21

Author(s):

Manuel V. Borca ◽

Elizabeth Ramirez-Medina ◽

Ediane Silva ◽

Elizabeth Vuono ◽

Ayushi Rai ◽

...

Keyword(s):

East Asia ◽

Central Europe ◽

Vaccine Candidate ◽

African Swine Fever Virus ◽

Dose Range ◽

African Swine Fever ◽

Fever Virus ◽

Swine Industry ◽

Virus Shedding ◽

Clinically Normal

ABSTRACT African swine fever virus (ASFV) is the etiological agent of a contagious and often lethal disease of domestic pigs that has significant economic consequences for the swine industry. The disease is devastating the swine industry in Central Europe and East Asia, with current outbreaks caused by circulating strains of ASFV derived from the 2007 Georgia isolate (ASFV-G), a genotype II ASFV. In the absence of any available vaccines, African swine fever (ASF) outbreak containment relies on the control and culling of infected animals. Limited cross-protection studies suggest that in order to ensure a vaccine is effective, it must be derived from the current outbreak strain or at the very least from an isolate with the same genotype. Here, we report the discovery that the deletion of a previously uncharacterized gene, I177L, from the highly virulent ASFV-G produces complete virus attenuation in swine. Animals inoculated intramuscularly with the virus lacking the I177L gene, ASFV-G-ΔI177L, at a dose range of 102 to 106 50% hemadsorbing doses (HAD50), remained clinically normal during the 28-day observational period. All ASFV-G-ΔI177L-infected animals had low viremia titers, showed no virus shedding, and developed a strong virus-specific antibody response; importantly, they were protected when challenged with the virulent parental strain ASFV-G. ASFV-G-ΔI177L is one of the few experimental vaccine candidate virus strains reported to be able to induce protection against the ASFV Georgia isolate, and it is the first vaccine capable of inducing sterile immunity against the current ASFV strain responsible for recent outbreaks. IMPORTANCE Currently, there is no commercially available vaccine against African swine fever. Outbreaks of this disease are devastating the swine industry from Central Europe to East Asia, and they are being caused by circulating strains of African swine fever virus derived from the Georgia 2007 isolate. Here, we report the discovery of a previously uncharacterized virus gene, which when deleted completely attenuates the Georgia isolate. Importantly, animals infected with this genetically modified virus were protected from developing ASF after challenge with the virulent parental virus. Interestingly, ASFV-G-ΔI177L confers protection even at low doses (102 HAD50) and remains completely attenuated when inoculated at high doses (106 HAD50), demonstrating its potential as a safe vaccine candidate. At medium or higher doses (104 HAD50), sterile immunity is achieved. Therefore, ASFV-G-ΔI177L is a novel efficacious experimental ASF vaccine protecting pigs from the epidemiologically relevant ASFV Georgia isolate.

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