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African Swine Fever Virus Prevention and Control

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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 January 2021) | Viewed by 69163

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Special Issue Editor

Dr. Christopher Netherton

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Guest Editor

african Swine Fever Vaccinology Group, The Pirbright Institute, Surrey GU24 0NF, UK
Interests: African swine fever; vaccines; host-pathogen interactions; virus assembly and replication; protective immunity; antigen discovery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Since its introduction into Georgia in 2007, African swine fever virus has spread across both Europe and Asia and has been responsible for the deaths of hundreds of millions of animals. Virulent strains of the virus cause a haemorhagic fever to occur in domestic pigs and wild boar that is invariably fatal. Current control measures based on rapid diagnosis, quarantine, and slaughter of affected animals have not been sufficient to prevent the disease from becoming established in different epidemiological situations across the globe. The main tools missing from the African swine fever control kit are vaccines suitable for preventing disease in both domestic and wild animals. Without such vaccines, it is difficult to envisage how the current epidemic can be brought under control and the disease eradicated. Novel approaches are required, as, to date, inactivated viruses and attenutation through tissue culture passage have not yielded safe and effective vaccines. The causative agent is a complex pathogen with a complex immunopathology that is not well-characterized. Mechanisms of protective immunity and protective antigens also remain to be fully described. Due to the severity of the current African swine fever virus epidemic, alternative strategies including prophylaxsis may also need to be considered. Deployment of such novel control strategies will require the development of effective implementaiton strategies based on robust epidemiological modeling.

Dr. Christopher Netherton
Guest Editor

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Keywords

African swine fever vaccines
African swine fever prophalyxsis
vaccine delivery to swine
vaccine deployment strategies
African swine fever virus protective immunity
African swine fever antigen discovery and characterization

Published Papers (13 papers)

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Research

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14 pages, 2204 KiB

Open AccessArticle

High Doses of Inactivated African Swine Fever Virus Are Safe, but Do Not Confer Protection against a Virulent Challenge

by Estefanía Cadenas-Fernández, Jose M. Sánchez-Vizcaíno, Erwin van den Born, Aleksandra Kosowska, Emma van Kilsdonk, Paloma Fernández-Pacheco, Carmina Gallardo, Marisa Arias and Jose A. Barasona

Vaccines 2021, 9(3), 242; https://doi.org/10.3390/vaccines9030242 - 10 Mar 2021

Cited by 34 | Viewed by 3377

Abstract

African swine fever (ASF) is currently the major concern of the global swine industry, as a consequence of which a reconsideration of the containment and prevention measures taken to date is urgently required. A great interest in developing an effective and safe vaccine against ASF virus (ASFV) infection has, therefore, recently appeared. The objective of the present study is to test an inactivated ASFV preparation under a vaccination strategy that has not previously been tested in order to improve its protective effect. The following have been considered: (i) virus inactivation by using a low binary ethyleneimine (BEI) concentration at a low temperature, (ii) the use of new and strong adjuvants; (iii) the use of very high doses (6 × 10⁹ haemadsorption in 50% of infected cultures (HAD₅₀)), and (iv) simultaneous double inoculation by two different routes of administration: intradermal and intramuscular. Five groups of pigs were, therefore, inoculated with BEI- Pol16/DP/OUT21 in different adjuvant formulations, twice with a 4-week interval. Six weeks later, all groups were intramuscularly challenged with 10 HAD₅₀ of the virulent Pol16/DP/OUT21 ASFV isolate. All the animals had clinical signs and pathological findings consistent with ASF. This lack of effectiveness supports the claim that an inactivated virus strategy may not be a viable vaccine option with which to fight ASF. Full article

(This article belongs to the Special Issue African Swine Fever Virus Prevention and Control)

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20 pages, 745 KiB

Open AccessArticle

Identification of Promiscuous African Swine Fever Virus T-Cell Determinants Using a Multiple Technical Approach

by Laia Bosch-Camós, Elisabet López, María Jesús Navas, Sonia Pina-Pedrero, Francesc Accensi, Florencia Correa-Fiz, Chankyu Park, Montserrat Carrascal, Javier Domínguez, Maria Luisa Salas, Veljko Nikolin, Javier Collado and Fernando Rodríguez

Vaccines 2021, 9(1), 29; https://doi.org/10.3390/vaccines9010029 - 7 Jan 2021

Cited by 17 | Viewed by 4818

Abstract

The development of subunit vaccines against African swine fever (ASF) is mainly hindered by the lack of knowledge regarding the specific ASF virus (ASFV) antigens involved in protection. As a good example, the identity of ASFV-specific CD8⁺ T-cell determinants remains largely unknown, despite their protective role being established a long time ago. Aiming to identify them, we implemented the IFNγ ELISpot as readout assay, using as effector cells peripheral blood mononuclear cells (PBMCs) from pigs surviving experimental challenge with Georgia2007/1. As stimuli for the ELISpot, ASFV-specific peptides or full-length proteins identified by three complementary strategies were used. In silico prediction of specific CD8⁺ T-cell epitopes allowed identifying a 19-mer peptide from MGF100-1L, as frequently recognized by surviving pigs. Complementarily, the repertoire of SLA I-bound peptides identified in ASFV-infected porcine alveolar macrophages (PAMs), allowed the characterization of five additional SLA I-restricted ASFV-specific epitopes. Finally, in vitro stimulation studies using fibroblasts transfected with plasmids encoding full-length ASFV proteins, led to the identification of MGF505-7R, A238L and MGF100-1L as promiscuously recognized antigens. Interestingly, each one of these proteins contain individual peptides recognized by surviving pigs. Identification of the same ASFV determinants by means of such different approaches reinforce the results presented here. Full article

(This article belongs to the Special Issue African Swine Fever Virus Prevention and Control)

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15 pages, 2685 KiB

Open AccessArticle

Standardized Methodology for Target Surveillance against African Swine Fever

by Stefano Cappai, Sandro Rolesu, Francesco Feliziani, Pietro Desini, Vittorio Guberti and Federica Loi

Vaccines 2020, 8(4), 723; https://doi.org/10.3390/vaccines8040723 - 2 Dec 2020

Cited by 12 | Viewed by 2636

Abstract

African swine fever (ASF) remains the most serious pig infectious disease, and its persistence in domestic pigs and wild boar (WB) is a threat for the global industry. The surveillance of WB plays a central role in controlling the disease and rapidly detecting new cases. As we are close to eradicating ASF, the need to find any possible pockets of infection is even more important. In this context, passive surveillance is the method of choice for effective surveillance in WB. Considering the time and economic resources related to passive surveillance, to prioritize these activities, we developed a standardized methodology able to identify areas where WB surveillance should be focused on. Using GIS-technology, we divided a specific Sardinian infected area into 1 km² grids (a total of 3953 grids). Variables related to WB density, ASF cases during the last three years, sex and age of animals, and the type of land were associated with each grid. Epidemiological models were used to identify the areas with both a lack of information and an high risk of hidden ASFV persistence. The results led to the creation of a graphic tool providing specific indications about areas where surveillance should be a priority. Full article

(This article belongs to the Special Issue African Swine Fever Virus Prevention and Control)

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25 pages, 6045 KiB

Open AccessArticle

Identification and Isolation of Two Different Subpopulations Within African Swine Fever Virus Arm/07 Stock

by Daniel Pérez-Núñez, Eva Castillo-Rosa, Gonzalo Vigara-Astillero, Raquel García-Belmonte, Carmina Gallardo and Yolanda Revilla

Vaccines 2020, 8(4), 625; https://doi.org/10.3390/vaccines8040625 - 25 Oct 2020

Cited by 18 | Viewed by 3642

Abstract

No efficient vaccines exist against African swine fever virus (ASFV), which causes a serious disease in wild boars and domestic pigs that produces great industrial and ecological concerns worldwide. An extensive genetic characterization of the original ASFV stocks used to produce live attenuated vaccine (LAV) prototypes is needed for vaccine biosecurity and control. Here, we sequenced for the first time the Arm/07 stock which was obtained from an infected pig during the Armenia outbreak in 2007, using an improved viral dsDNA purification method together with high coverage analysis. There was unexpected viral heterogeneity within the stock, with two genetically distinct ASFV subpopulations. The first, represented by the Arm/07/CBM/c2 clone, displayed high sequence identity to the updated genotype II Georgia 2007/1, whereas the second (exemplified by clone Arm/07/CBM/c4) displayed a hemadsorbing phenotype and grouped within genotype I based on a central region conserved among all members of this group. Intriguingly, Arm/07/CBM/c4 contained a unique EP402R sequence, produced by a single mutation in the N-terminal region. Importantly, Arm/07/CBM/c4 showed in vitro features of attenuated strains regarding innate immune response pathway. Both Arm/07/CBM/c2 and c4 represent well-characterized viral clones, useful for different molecular and virus-host interaction studies, including virulence studies and vaccine development. Full article

(This article belongs to the Special Issue African Swine Fever Virus Prevention and Control)

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18 pages, 1461 KiB

Open AccessArticle

African Swine Fever Circulation among Free-Ranging Pigs in Sardinia: Data from the Eradication Program

by Giulia Franzoni, Silvia Dei Giudici, Federica Loi, Daria Sanna, Matteo Floris, Mariangela Fiori, Maria Luisa Sanna, Paola Madrau, Fabio Scarpa, Susanna Zinellu, Monica Giammarioli, Stefano Cappai, Gian Mario De Mia, Alberto Laddomada, Sandro Rolesu and Annalisa Oggiano

Vaccines 2020, 8(3), 549; https://doi.org/10.3390/vaccines8030549 - 21 Sep 2020

Cited by 26 | Viewed by 4780

Abstract

African swine fever virus (ASFV), the cause of a devastating disease affecting domestic and wild pigs, has been present in Sardinia since 1978. In the framework of the regional ASF eradication plan, 4484 illegal pigs were culled between December 2017 and February 2020. The highest disease prevalence was observed in the municipality with the highest free-ranging pig density, and culling actions drastically reduced ASFV circulation among these animals. ASFV-antibody were detected in 36.7% of tested animals, which were apparently healthy, thus, the circulation of low-virulence ASFV isolates was hypothesized. ASFV genome was detected in 53 out of 2726 tested animals, and virus isolation was achieved in two distinct culling actions. Two ASFV haemadsorbing strains were isolated from antibody-positive apparently healthy pigs: 55234/18 and 103917/18. Typing analysis revealed that both isolates belong to p72 genotype I, B602L subgroup X; phylogenetic analysis based on whole genome sequencing data showed that they were closely related to Sardinian ASFV strains collected since 2010, especially 22653/Ca/2014. Our data suggested the absence of immune-escaped ASFV variants circulating among free-ranging pigs, indicating that other elements contributed to virus circulation among these animals. Understanding factors behind disease persistence in endemic settings might contribute to developing effective countermeasures against this disease. Full article

(This article belongs to the Special Issue African Swine Fever Virus Prevention and Control)

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20 pages, 4846 KiB

Open AccessArticle

Mathematical Approach to Estimating the Main Epidemiological Parameters of African Swine Fever in Wild Boar

by Federica Loi, Stefano Cappai, Alberto Laddomada, Francesco Feliziani, Annalisa Oggiano, Giulia Franzoni, Sandro Rolesu and Vittorio Guberti

Vaccines 2020, 8(3), 521; https://doi.org/10.3390/vaccines8030521 - 12 Sep 2020

Cited by 25 | Viewed by 4130

Abstract

African swine fever (ASF) severely threatens the swine industry worldwide, given its spread and the absence of an available licensed vaccine, and has caused severe economic losses. Its persistence in wild boar (WB), longer than in domestic pig farms, and the knowledge gaps in ASF epidemiology hinder ASF virus (ASFV) eradication. Even in areas where disease is effectively controlled and ASFV is no longer detected, declaring eradication is difficult as seropositive WBs may still be detected. The aim of this work was to estimate the main ASF epidemiological parameters specific for the north of Sardinia, Italy. The estimated basic (R₀) and effective (R_e) reproduction numbers demonstrate that the ASF epidemic is declining and under control with an R₀ of 1.139 (95% confidence interval (CI) = 1.123–1.153) and R_e of 0.802 (95% CI = 0.612–0.992). In the last phases of an epidemic, these estimates are crucial tools for identifying the intensity of interventions required to definitively eradicate the disease. This approach is useful to understand if and when the detection of residual seropositive WB is no longer associated with any further ASFV circulation. Full article

(This article belongs to the Special Issue African Swine Fever Virus Prevention and Control)

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14 pages, 1682 KiB

Open AccessArticle

How to Demonstrate Freedom from African Swine Fever in Wild Boar—Estonia as an Example

by Katja Schulz, Christoph Staubach, Sandra Blome, Imbi Nurmoja, Arvo Viltrop, Franz J. Conraths, Maarja Kristian and Carola Sauter-Louis

Vaccines 2020, 8(2), 336; https://doi.org/10.3390/vaccines8020336 - 25 Jun 2020

Cited by 23 | Viewed by 3753

Abstract

Estonia has been combatting African swine fever (ASF) for six years now. Since October 2017, the disease has only been detected in the wild boar population, but trade restrictions had to remain in place due to international regulations. Yet, the epidemiological course of the disease has changed within the last few years. The prevalence of ASF virus (ASFV)-positive wild boar decreased steadily towards 0%. In February 2019, the last ASFV-positive wild boar was detected. Since then, positive wild boar samples have exclusively been positive for ASFV-specific antibodies, suggesting the possible absence of circulating ASFV in the Estonian wild boar population. However, as the role of seropositive animals is controversially discussed and the presence of antibody-carriers is regarded as an indication of virus circulation at EU and OIE level, Estonia remains under trade restrictions. To make the disease status of a country reliable for trading partners and to facilitate the process of declaration of disease freedom, we suggest to monitor the prevalence of seropositive wild boar in absence of ASFV-positive animals. The possibility to include ASF in the list of diseases, for which an official pathway for recognition of disease status is defined by the OIE should be evaluated. Full article

(This article belongs to the Special Issue African Swine Fever Virus Prevention and Control)

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15 pages, 2890 KiB

Open AccessArticle

Deletion of the Gene for the Type I Interferon Inhibitor I329L from the Attenuated African Swine Fever Virus OURT88/3 Strain Reduces Protection Induced in Pigs

by Ana Luisa Reis, Lynnette C. Goatley, Tamara Jabbar, Elisabeth Lopez, Anusyah Rathakrishnan and Linda K. Dixon

Vaccines 2020, 8(2), 262; https://doi.org/10.3390/vaccines8020262 - 30 May 2020

Cited by 28 | Viewed by 3666

Abstract

Live attenuated vaccines are considered to be the fastest route to the development of a safe and efficacious African swine fever (ASF) vaccine. Infection with the naturally attenuated OURT88/3 strain induces protection against challenge with virulent isolates from the same or closely related genotypes. However, adverse clinical signs following immunisation have been observed. Here, we attempted to increase the OURT88/3 safety profile by deleting I329L, a gene previously shown to inhibit the host innate immune response. The resulting virus, OURT88/3ΔI329L, was tested in vitro to evaluate the replication and expression of type I interferon (IFN) and in vivo by immunisation and lethal challenge experiments in pigs. No differences were observed regarding replication; however, increased amounts of both IFN-β and IFN-α were observed in macrophages infected with the deletion mutant virus. Unexpectedly, the deletion of I329L markedly reduced protection against challenge with the virulent OURT88/1 isolate. This was associated with a decrease in both antibody levels against VP72 and the number of IFN-γ-producing cells in the blood of non-protected animals. Furthermore, a significant increase in IL-10 levels in serum was observed in pigs immunised with OURT88/3ΔI329L following challenge. Interestingly, the deletion of the I329L gene failed to attenuate the virulent Georgia/2007 isolate. Full article

(This article belongs to the Special Issue African Swine Fever Virus Prevention and Control)

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26 pages, 5702 KiB

Open AccessArticle

A Pool of Eight Virally Vectored African Swine Fever Antigens Protect Pigs against Fatal Disease

by Lynnette C. Goatley, Ana Luisa Reis, Raquel Portugal, Hannah Goldswain, Gareth L. Shimmon, Zoe Hargreaves, Chak-Sum Ho, María Montoya, Pedro J. Sánchez-Cordón, Geraldine Taylor, Linda K. Dixon and Christopher L. Netherton

Vaccines 2020, 8(2), 234; https://doi.org/10.3390/vaccines8020234 - 18 May 2020

Cited by 69 | Viewed by 12275

Abstract

Classical approaches to African swine fever virus (ASFV) vaccine development have not been successful; inactivated virus does not provide protection and use of live attenuated viruses generated by passage in tissue culture had a poor safety profile. Current African swine fever (ASF) vaccine research focuses on the development of modified live viruses by targeted gene deletion or subunit vaccines. The latter approach would be differentiation of vaccinated from infected animals (DIVA)-compliant, but information on which viral proteins to include in a subunit vaccine is lacking. Our previous work used DNA-prime/vaccinia-virus boost to screen 40 ASFV genes for immunogenicity, however this immunization regime did not protect animals after challenge. Here we describe the induction of both antigen and ASFV-specific antibody and cellular immune responses by different viral-vectored pools of antigens selected based on their immunogenicity in pigs. Immunization with one of these pools, comprising eight viral-vectored ASFV genes, protected 100% of pigs from fatal disease after challenge with a normally lethal dose of virulent ASFV. This data provide the basis for the further development of a subunit vaccine against this devastating disease. Full article

(This article belongs to the Special Issue African Swine Fever Virus Prevention and Control)

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Review

Jump to: Research

20 pages, 392 KiB

Open AccessReview

With or without a Vaccine—A Review of Complementary and Alternative Approaches to Managing African Swine Fever in Resource-Constrained Smallholder Settings

by Mary-Louise Penrith, Armanda Bastos and Erika Chenais

Vaccines 2021, 9(2), 116; https://doi.org/10.3390/vaccines9020116 - 2 Feb 2021

Cited by 25 | Viewed by 4162

Abstract

The spectacular recent spread of African swine fever (ASF) in Eastern Europe and Asia has been strongly associated, as it is in the endemic areas in Africa, with free-ranging pig populations and low-biosecurity backyard pig farming. Managing the disease in wild boar populations and in circumstances where the disease in domestic pigs is largely driven by poverty is particularly challenging and may remain so even in the presence of effective vaccines. The only option currently available to prevent ASF is strict biosecurity. Among small-scale pig farmers biosecurity measures are often considered unaffordable or impossible to implement. However, as outbreaks of ASF are also unaffordable, the adoption of basic biosecurity measures is imperative to achieve control and prevent losses. Biosecurity measures can be adapted to fit smallholder contexts, culture and costs. A longer-term approach that could prove valuable particularly for free-ranging pig populations would be exploitation of innate resistance to the virus, which is fully effective in wild African suids and has been observed in some domestic pig populations in areas of prolonged endemicity. We explore available options for preventing ASF in terms of feasibility, practicality and affordability among domestic pig populations that are at greatest risk of exposure to ASF. Full article

(This article belongs to the Special Issue African Swine Fever Virus Prevention and Control)

17 pages, 1939 KiB

Open AccessReview

Role of the DNA-Binding Protein pA104R in ASFV Genome Packaging and as a Novel Target for Vaccine and Drug Development

by Ana Catarina Urbano and Fernando Ferreira

Vaccines 2020, 8(4), 585; https://doi.org/10.3390/vaccines8040585 - 3 Oct 2020

Cited by 17 | Viewed by 5172

Abstract

The recent incursions of African swine fever (ASF), a severe, highly contagious, transboundary viral disease that affects members of the Suidae family, in Europe and China have had a catastrophic impact on trade and pig production, with serious implications for global food security. Despite efforts made over past decades, there is no vaccine or treatment available for preventing and controlling the ASF virus (ASFV) infection, and there is an urgent need to develop novel strategies. Genome condensation and packaging are essential processes in the life cycle of viruses. The involvement of viral DNA-binding proteins in the regulation of virulence genes, transcription, DNA replication, and repair make them significant targets. pA104R is a highly conserved HU/IHF-like DNA-packaging protein identified in the ASFV nucleoid that appears to be profoundly involved in the spatial organization and packaging of the ASFV genome. Here, we briefly review the components of the ASFV packaging machinery, the structure, function, and phylogeny of pA104R, and its potential as a target for vaccine and drug development. Full article

(This article belongs to the Special Issue African Swine Fever Virus Prevention and Control)

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27 pages, 1099 KiB

Open AccessReview

Current State of Global African Swine Fever Vaccine Development under the Prevalence and Transmission of ASF in China

by Keke Wu, Jiameng Liu, Lianxiang Wang, Shuangqi Fan, Zhaoyao Li, Yuwan Li, Lin Yi, Hongxing Ding, Mingqiu Zhao and Jinding Chen

Vaccines 2020, 8(3), 531; https://doi.org/10.3390/vaccines8030531 - 15 Sep 2020

Cited by 79 | Viewed by 10056

Abstract

African swine fever (ASF) is a highly lethal contagious disease of swine caused by African swine fever virus (ASFV). At present, it is listed as a notifiable disease reported to the World Organization for Animal Health (OIE) and a class one animal disease ruled by Chinese government. ASF has brought significant economic losses to the pig industry since its outbreak in China in August 2018. In this review, we recapitulated the epidemic situation of ASF in China as of July 2020 and analyzed the influencing factors during its transmission. Since the situation facing the prevention, control, and eradication of ASF in China is not optimistic, safe and effective vaccines are urgently needed. In light of the continuous development of ASF vaccines in the world, the current scenarios and evolving trends of ASF vaccines are emphatically analyzed in the latter part of the review. The latest research outcomes showed that attempts on ASF gene-deleted vaccines and virus-vectored vaccines have proven to provide complete homologous protection with promising efficacy. Moreover, gaps and future research directions of ASF vaccine are also discussed. Full article

(This article belongs to the Special Issue African Swine Fever Virus Prevention and Control)

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16 pages, 447 KiB

Open AccessReview

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

by João Coelho and Alexandre Leitão

Vaccines 2020, 8(2), 312; https://doi.org/10.3390/vaccines8020312 - 17 Jun 2020

Cited by 14 | Viewed by 4341

Abstract

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. Full article

(This article belongs to the Special Issue African Swine Fever Virus Prevention and Control)

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