scholarly journals Current efforts towards safe and effective live attenuated vaccines against African swine fever: challenges and prospects

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Tao Wang ◽  
Rui Luo ◽  
Yuan Sun ◽  
Hua-Ji Qiu
Keyword(s):  
Prevention And Control ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Field Application ◽  
Stable Cell Line ◽  
Effective Vaccine ◽  
Hemorrhagic Disease ◽  
Wide Field ◽  
Live Attenuated Vaccines ◽  
And Control

Abstract Background African swine fever (ASF) is a fatal hemorrhagic disease in domestic pigs and wild boar caused by African swine fever virus (ASFV). Since ASF has been introduced into Europe and Asia, the major pig-raising areas, posing a huge threat to the pork industry worldwide. Currently, prevention and control of ASF are basically dependent on strict biosecurity measures and stamping-out policy once ASF occurs. Main text The major risks of ASF spread are insufficient biosecurity measures and human behaviors. Therefore, a safe and effective vaccine seems to be a reasonable demand for the prevention and control of ASF. Due to the efficacy advantage over other types of vaccines, live attenuated vaccines (LAVs), especially virulence-associated genes deleted vaccines, are likely to be put into emergency and conditional use in restricted areas if ASF is out of control in a country with a huge pig population and pork consumption, like China. However, the safety, efficacy, and genetic stability of current candidate ASF LAVs require comprehensive clinical evaluations prior to country-wide field application. Several critical issues need to be addressed to commercialize an ideal ASF LAV, including a stable cell line for manufacturing vaccines, differentiation of infected from vaccinated animals (DIVA), and cross-protection from different genotypes. Conclusion A safe and effective DIVA vaccine and an accompanying diagnostic assay will facilitate the prevention, control, and eradication of ASF, which is quite challenging in the near future. Graphical Abstract

scholarly journals African Swine Fever Virus A528R Inhibits TLR8 Mediated NF-κB Activity by Targeting p65 Activation and Nuclear Translocation

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2046
Author(s):  
Xueliang Liu ◽  
Da Ao ◽  
Sen Jiang ◽  
Nengwen Xia ◽  
Yulin Xu ◽  
...  
Keyword(s):  
Promoter Activity ◽  
Nuclear Translocation ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Viral Proteins ◽  
Fever Virus ◽  
Economic Losses ◽  
Effective Vaccine ◽  
Hemorrhagic Disease ◽  
Host Innate Immunity

African swine fever (ASF) is mainly an acute hemorrhagic disease which is highly contagious and lethal to domestic pigs and wild boars. The global pig industry has suffered significant economic losses due to the lack of an effective vaccine and treatment. The African swine fever virus (ASFV) has a large genome of 170–190 kb, encoding more than 150 proteins. During infection, ASFV evades host innate immunity via multiple viral proteins. A528R is a very important member of the polygene family of ASFV, which was shown to inhibit IFN-β production by targeting NF-κB, but its mechanism is not clear. This study has shown that A528R can suppress the TLR8-NF-κB signaling pathway, including the inhibition of downstream promoter activity, NF-κB p65 phosphorylation and nuclear translocation, and the antiviral and antibacterial activity. Further, we found the cellular co-localization and interaction between A528R and p65, and ANK repeat domains of A528R and RHD of p65 are involved in their interaction and the inhibition of p65 activity. Therefore, we conclude that A528R inhibits TLR8-NF-κB signaling by targeting p65 activation and nuclear translocation.

scholarly journals Prevention and Control Strategies of African Swine Fever and Progress on Pig Farm Repopulation in China

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2552
Author(s):  
Yuanjia Liu ◽  
Xinheng Zhang ◽  
Wenbao Qi ◽  
Yaozhi Yang ◽  
Zexin Liu ◽  
...  
Keyword(s):  
Prevention And Control ◽  
African Swine Fever Virus ◽  
Control Strategies ◽  
African Swine Fever ◽  
Research Progress ◽  
Pork Industry ◽  
Wild Pigs ◽  
Pig Farm ◽  
Sources Of Infection ◽  
And Control

African swine fever (ASF) is a devastating disease in domestic and wild pigs. Since the first outbreak of ASF in August 2018 in China, the disease has spread throughout the country with an unprecedented speed, causing heavy losses to the pig and related industries. As a result, strategies for managing the disease are urgently needed. This paper summarizes the important aspects of three key elements about African swine fever virus (ASFV) transmission, including the sources of infection, transmission routes, and susceptible animals. It overviews the relevant prevention and control strategies, focusing on the research progress of ASFV vaccines, anti-ASFV drugs, ASFV-resistant pigs, efficient disinfection, and pig farm biosecurity. We then reviewed the key technical points concerning pig farm repopulation, which is critical to the pork industry. We hope to not only provide a theoretical basis but also practical strategies for effective dealing with the ASF epidemic and restoration of pig production.

scholarly journals The African Swine Fever Virus (ASFV) Topoisomerase II as a Target for Viral Prevention and Control

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 312 ◽  
Author(s):  
João Coelho ◽  
Alexandre Leitão
Keyword(s):  
Topoisomerase Ii ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Fever Virus ◽  
Effective Vaccine ◽  
Type Ii ◽  
Cancer Treatments ◽  
Promising Target ◽  
Multicellular Organisms ◽  
And Control

African swine fever (ASF) is, once more, spreading throughout the world. After its recent reintroduction in Georgia, it quickly reached many neighboring countries in Eastern Europe. It was also detected in Asia, infecting China, the world’s biggest pig producer, and spreading to many of the surrounding countries. Without any vaccine or effective treatment currently available, new strategies for the control of the disease are mandatory. Its etiological agent, the African swine fever virus (ASFV), has been shown to code for a type II DNA topoisomerase. These are enzymes capable of modulating the topology of DNA molecules, known to be essential in unicellular and multicellular organisms, and constitute targets in antibacterial and anti-cancer treatments. In this review, we summarize most of what is known about this viral enzyme, pP1192R, and discuss about its possible role(s) during infection. Given the essential role of type II topoisomerases in cells, the data so far suggest that pP1192R is likely to be equally essential for the virus and thus a promising target for the elaboration of a replication-defective virus, which could provide the basis for an effective vaccine. Furthermore, the use of inhibitors could be considered to control the spread of the infection during outbreaks and therefore limit the spreading of the disease.

scholarly journals Generation and Evaluation of an African Swine Fever Virus Mutant with Deletion of the CD2v and UK Genes

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 763
Author(s):  
Teshale Teklue ◽  
Tao Wang ◽  
Yuzi Luo ◽  
Rongliang Hu ◽  
Yuan Sun ◽  
...  
Keyword(s):  
African Swine Fever Virus ◽  
Clinical Signs ◽  
African Swine Fever ◽  
Virus Genome ◽  
Fever Virus ◽  
Effective Vaccine ◽  
Post Inoculation ◽  
Virus Mutant ◽  
And Control

African swine fever (ASF) is a highly contagious and often lethal disease caused by African swine fever virus (ASFV). ASF emerged in China in August 2018 and has since rapidly spread into many areas of the country. The disease has caused a significant impact on China’s pig and related industries. A safe and effective vaccine is needed to prevent and control the disease. Several gene-deleted ASFVs have been reported; however, none of them is safe enough and commercially available. In this study, we report the generation of a double gene-deleted ASFV mutant, ASFV-SY18-∆CD2v/UK, from a highly virulent field strain ASFV-SY18 isolated in China. The results showed that ASFV-SY18-∆CD2v/UK lost hemadsorption properties, and the simultaneous deletion of the two genes did not significantly affect the in vitro replication of the virus in primary porcine alveolar macrophages. Furthermore, ASFV-SY18-∆CD2v/UK was attenuated in pigs. All the ASFV-SY18-∆CD2v/UK-inoculated pigs remained healthy, and none of them developed ASF-associated clinical signs. Additionally, the ASFV-SY18-∆CD2v/UK-infected pigs developed ASFV-specific antibodies, and no virus genome was detected in blood and nasal discharges at 21 and 28 days post-inoculation. More importantly, we found that all the pigs inoculated with 104 TCID50 of ASFV-SY18-∆CD2v/UK were protected against the challenge with the parental ASFV-SY18. However, low-level ASFV DNA was detected in blood, nasal swabs, and lymphoid tissue after the challenge. The results demonstrate that ASFV-SY18-∆CD2v/UK is safe and able to elicit protective immune response in pigs and can be a potential vaccine candidate to control ASF.

scholarly journals African Swine Fever Virus as a Difficult Opponent in the Fight for a Vaccine—Current Data

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1212
Author(s):  
Hanna Turlewicz-Podbielska ◽  
Anna Kuriga ◽  
Rafał Niemyjski ◽  
Grzegorz Tarasiuk ◽  
Małgorzata Pomorska-Mól
Keyword(s):  
African Swine Fever Virus ◽  
Complex Structure ◽  
African Swine Fever ◽  
Biological Properties ◽  
Current Data ◽  
Fever Virus ◽  
Effective Vaccine ◽  
Targeted Gene Deletion ◽  
The Many ◽  
And Control

Prevention and control of African swine fever virus (ASFV) in Europe, Asia, and Africa seem to be extremely difficult in view of the ease with which it spreads, its high resistance to environmental conditions, and the many obstacles related to the introduction of effective specific immunoprophylaxis. Biological properties of ASFV indicate that the African swine fever (ASF) pandemic will continue to develop and that only the implementation of an effective and safe vaccine will ensure a reduction in the spread of ASFV. At present, vaccines against ASF are not available. The latest approaches to the ASFV vaccine’s design concentrate on the development of either modified live vaccines by targeted gene deletion from different isolates or subunit vaccines. The construction of an effective vaccine is hindered by the complex structure of the virus, the lack of an effective continuous cell line for the isolation and propagation of ASFV, unpredictable and stain-specific phenotypes after the genetic modification of ASFV, a risk of reversion to virulence, and our current inability to differentiate infected animals from vaccinated ones. Moreover, the design of vaccines intended for wild boars and oral administration is desirable. Despite several obstacles, the design of a safe and effective vaccine against ASFV seems to be achievable.

scholarly journals Computational Analysis of African Swine Fever Virus Protein Space for the Design of an Epitope-Based Vaccine Ensemble

Pathogens ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1078 ◽  
Author(s):  
Albert Ros-Lucas ◽  
Florencia Correa-Fiz ◽  
Laia Bosch-Camós ◽  
Fernando Rodriguez ◽  
Julio Alonso-Padilla
Keyword(s):  
T Cell ◽  
Vaccine Development ◽  
De Novo ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Fever Virus ◽  
Economic Losses ◽  
Virus Protein ◽  
Hemorrhagic Disease ◽  
Starting Point

African swine fever virus is the etiological agent of African swine fever, a transmissible severe hemorrhagic disease that affects pigs, causing massive economic losses. There is neither a treatment nor a vaccine available, and the only method to control its spread is by extensive culling of pigs. So far, classical vaccine development approaches have not yielded sufficiently good results in terms of concomitant safety and efficacy. Nowadays, thanks to advances in genomic and proteomic techniques, a reverse vaccinology strategy can be explored to design alternative vaccine formulations. In this study, ASFV protein sequences were analyzed using an in-house pipeline based on publicly available immunoinformatic tools to identify epitopes of interest for a prospective vaccine ensemble. These included experimentally validated sequences from the Immune Epitope Database, as well as de novo predicted sequences. Experimentally validated and predicted epitopes were prioritized following a series of criteria that included evolutionary conservation, presence in the virulent and currently circulating variant Georgia 2007/1, and lack of identity to either the pig proteome or putative proteins from pig gut microbiota. Following this strategy, 29 B-cell, 14 CD4+ T-cell and 6 CD8+ T-cell epitopes were selected, which represent a starting point to investigating the protective capacity of ASFV epitope-based vaccines.

scholarly journals African Swine Fever Laboratory Diagnosis—Lessons Learned from Recent Animal Trials

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 177
Author(s):  
Jutta Pikalo ◽  
Paul Deutschmann ◽  
Melina Fischer ◽  
Hanna Roszyk ◽  
Martin Beer ◽  
...  
Keyword(s):  
African Swine Fever Virus ◽  
Clinical Signs ◽  
African Swine Fever ◽  
Laboratory Diagnosis ◽  
Lessons Learned ◽  
Hemorrhagic Disease ◽  
Passive Surveillance ◽  
Animal Trials ◽  
Fit For Purpose ◽  
The Impact

African swine fever virus (ASFV) causes a hemorrhagic disease in pigs with high socio-economic consequences. To lower the impact of disease incursions, early detection is crucial. In the context of experimental animal trials, we evaluated diagnostic workflows for a high sample throughput in active surveillance, alternative sample matrices for passive surveillance, and lateral flow devices (LFD) for rapid testing. We could demonstrate that EDTA blood is significantly better suited for early ASFV detection than serum. Tissues recommended by the respective diagnostic manuals were in general comparable in their performance, with spleen samples giving best results. Superficial lymph nodes, ear punches, and different blood swabs were also evaluated as potential alternatives. In summary, all matrices yielded positive results at the peak of clinical signs and could be fit for purpose in passive surveillance. However, weaknesses were discovered for some matrices when it comes to the early phase of infection or recovery. The antigen LFD showed variable results with best performance in the clinical phase. The antibody LFD was quite comparable with ELISA systems. Concluding, alternative approaches are feasible but have to be embedded in control strategies selecting test methods and sample materials following a “fit-for-purpose” approach.

scholarly journals Cholesterol Flux Is Required for Endosomal Progression of African Swine Fever Virions during the Initial Establishment of Infection

2015 ◽  
Vol 90 (3) ◽  
pp. 1534-1543 ◽  
Author(s):  
Miguel Ángel Cuesta-Geijo ◽  
Michele Chiappi ◽  
Inmaculada Galindo ◽  
Lucía Barrado-Gil ◽  
Raquel Muñoz-Moreno ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Cholesterol Efflux ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Endocytic Pathway ◽  
Productive Infection ◽  
Effective Vaccine ◽  
The Caucasus ◽  
Late Endosomes ◽  
Adenovirus 5

ABSTRACTAfrican swine fever virus (ASFV) is a major threat for porcine production that has been slowly spreading in Eastern Europe since its first appearance in the Caucasus in 2007. ASFV enters the cell by endocytosis and gains access to the cytosol to start replication from late endosomes and multivesicular bodies. Cholesterol associated with low-density lipoproteins entering the cell by endocytosis also follows a trafficking pathway similar to that of ASFV. Here we show that cholesterol plays an essential role in the establishment of infection as the virus traffics through the endocytic pathway. In contrast to the case for other DNA viruses, such as vaccinia virus or adenovirus 5, cholesterol efflux from endosomes is required for ASFV release/entry to the cytosol. Accumulation of cholesterol in endosomes impairs fusion, resulting in retention of virions inside endosomes. ASFV also remodels intracellular cholesterol by increasing its cellular uptake and redistributes free cholesterol to viral replication sites. Our analysis reveals that ASFV manipulates cholesterol dynamics to ensure an appropriate lipid flux to establish productive infection.IMPORTANCESince its appearance in the Caucasus in 2007, African swine fever (ASF) has been spreading westwards to neighboring European countries, threatening porcine production. Due to the lack of an effective vaccine, ASF control relies on early diagnosis and widespread culling of infected animals. We investigated early stages of ASFV infection to identify potential cellular targets for therapeutic intervention against ASF. The virus enters the cell by endocytosis, and soon thereafter, viral decapsidation occurs in the acid pH of late endosomes. We found that ASFV infection requires and reorganizes the cellular lipid cholesterol. ASFV requires cholesterol to exit the endosome to gain access to the cytoplasm to establish productive replication. Our results indicate that there is a differential requirement for cholesterol efflux for vaccinia virus or adenovirus 5 compared to ASFV.

DNA segments of African Swine Fever Virus detected for the first time in hard ticks from sheep and bovines

2019 ◽  
Vol 24 (1) ◽  
pp. 180 ◽  
Author(s):  
Ze Chen ◽  
Xiaofeng Xu ◽  
Yufeng Wang ◽  
Jinlong Bei ◽  
Xiufeng Jin ◽  
...  
Keyword(s):  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Fever Virus ◽  
Control Measures ◽  
Single Amino Acid ◽  
Small Rna Sequencing ◽  
Hard Ticks ◽  
Prevention And Control Measures ◽  
And Control ◽  
First Time

In this study, we detected African Swine Fever Virus (ASFV) in Dermacentor (Ixodidae) from sheep and bovines using small RNA sequencing. To validate this result, a 235-bp DNA segment was detected in a number of DNA samples from D. silvarum and sheep blood. This 235-bp segment had an identity of 99% to a 235-bp DNA segment of ASFV and contained three single nucleotide mutations (C38T, C76T and A108C). C38T, resulting in a single amino acid mutation G66D, suggests the existence of a new ASFV strain, which is different from all reported ASFV strains in the NCBI GenBank database and the ASFV strain (GenBank: MH713612.1) reported in China in 2018. To further confirm the existence of ASFV in Dermacentor ticks, three DNA segments of ASFV were detected in D. niveus females from bovines and their first generation ticks reared in our lab. These results also proved that transovarian transmission of ASFV occurs in hard ticks. This study revealed for the first time that ASFV has a wider range of hosts (e.g. sheep and bovines) and vectors (e.g. hard ticks), beyond the well-known Suidae family and Argasidae (soft ticks). Our findings pave the way toward further studies on ASFV transmission and the development of prevention and control measures.

scholarly journals Development and clinical application of a novel CRISPR-Cas12a based assay for the detection of African swine fever virus

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaoying Wang ◽  
Sheng He ◽  
Na Zhao ◽  
Xiaohong Liu ◽  
Yongchang Cao ◽  
...  
Keyword(s):  
African Swine Fever Virus ◽  
Diagnostic Technique ◽  
African Swine Fever ◽  
Cross Reactivity ◽  
Fever Virus ◽  
Effective Vaccine ◽  
Highly Sensitive ◽  
Resource Poor ◽  
Good Consistency ◽  
Virus Genotypes

Abstract Background As no treatment or effective vaccine for African swine fever virus (ASFV) is currently available, a rapid, highly sensitive diagnostic is urgently needed to curb the spread of ASFV. Results Here we designed a novel CRISPR-Cas12a based assay for ASFV detection. To detect different ASFV genotypes, 19 crRNAs were designed to target the conserved p72 gene in ASFV, and several crRNAs with high activity were identified that could be used as alternatives in the event of new ASFV variants. The results showed that the sensitivity of the CRISPR-Cas12a based assay is about ten times higher than either the commercial quantitative PCR (qPCR) kit or the OIE-recommended qPCR. CRISPR-Cas12a based assay could also detect ASFV specifically without cross-reactivity with other important viruses in pigs and various virus genotypes. We also found that longer incubation times increased the detection limits, which could be applied to improve assay outcomes in the detection of weakly positive samples and new ASFV variants. In addition, both the CRISPR-Cas12a based assay and commercial qPCR showed very good consistency. Conclusions In summary, the CRISPR-Cas12a based assay offers a feasible approach and a new diagnostic technique for the diagnosis of ASFV, particularly in resource-poor settings.

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