Vaccines targeting African Swine Fever Virus

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (15 January 2020) | Viewed by 16738

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Dear Colleagues,

Although several measures such as quick diagnosis, control, and eradication have been implemented, African swine fever virus (ASFV) has expanded incredibly quickly from 2007, spreading through the EU and China, causing both serious damages to wild boar populations and domestic pigs as well as serious economic consequences.

African swine fever virus (ASFV), the only member of the Asfarviridae family, is a dsDNA virus of huge complexity and size that encodes more than 150 proteins, including both structural and host-induced immunoregulatory proteins. ASFV is the etiological agent of African swine fever (ASF), a devastating disease infecting swine monocytes and macrophages. An outbreak in the Caucasus in 2007 started the spread of ASFV across Russia and Eastern Europe, currently also affecting Ukraine, Belarus, Poland, the Baltic States, the Czech Republic, Moldova, Bulgaria, and Romania. The declaration of outbreaks in China, Luxembourg, and Belgium last August 2018 definitively enhances the serious drawback that the extension of ASF poses for the global swine industry. Despite progresses from several groups in building a vaccine, only control and eradication measures mostly based on early laboratory diagnostic detection and implementation of strict sanitary procedures are currently available. The rapid dissemination of the disease shows these actions to be clearly insufficient to control the current pandemic situation, and the development of a vaccine is urgently required.

Historically, unsuccessful attempts for the development of ASFV vaccines have involved inactivated viruses, recombinant proteins/peptides, viral vectors for antigen delivery, and live-attenuated vaccines. In brief, approaches to protect pigs using inactivated vaccines were ineffective, still combined with specific adjuvants, while subunit vaccines showed only partial protection against challenge with virulent ASFV strains. Other studies immunizing with a DNA expression library containing a number of viral ORFs fused to ubiquitin induced only partial protection against virulent challenge. Interestingly, vaccination with baculovirus-expressed ASFV proteins p30, p54, p72, and p22, although capable of inducing neutralizing antibodies in vivo, did not protect animals. Recent strategies based on the combination of both recombinant proteins and DNA vaccines, and the use of viral vector platforms such as adenovirus or MVA have recently been reported, although none confer full protection of the vaccinated animals.

Due to the overall failure of the protocols mentioned above, and given the challenging vaccination scenario, the so-called ‘‘live attenuated vaccine” (LAV) emerges as a putative strategy in protection.

In this regard, recombinant ASFVs containing specific deletions within virulence genes, such as EP402R, 9GL (B119L), members of multigene families 360 and 505 (MGF 360/505), DP148R or DP96R, have been generated to attenuate the parental virulent ASFV strains, inducing different levels of protection against homologous and heterologous virus challenge. However, the risk of vaccinating with genetically modified virus derived from virulent isolates is high, as processes of in vivo recombination between the recombinant vaccines and circulating virus in the animal could potentially generate a new virulent outbreak.

To avoid such hazardous possibility, the attenuated strains ASFV OURT88/3 and ASFV NH /P68, which have been shown to induce good levels of protection against homologous and heterologous virulent challenge, constitute an interesting and safer alternative, although they present undesirable side effects when inoculated in pigs.

Nonetheless, it is widely agreed that naturally attenuated strains cannot be used as vaccines without tracing them with specific tags and without including specific genomic modifications, including companion DIVA tests, allowing their use as live-attenuated vaccine (LAV) candidates. In this regard, three main concerns should be focused for vaccine development: a) avoiding the side effect consequences induced by the attenuated LAVs (i.e. joint swelling, necrotic foci, fever, and other clinical events typical of chronic disease); b) designing specific tests to differentiate between infected and vaccinated animals (DIVA); and c) generation of cell lines useful to sustain the production of this kind of vaccine prototypes.

Finally, the rationale of the ASFV/LAVs vaccine prototypes production needs to be validated on pigs and wild boars to test their efficacy. This should be achieved either in BSL-3 facilities or in field conditions, which importantly engage experimentation and results in high costs.

Dr. Yolanda Revilla Novella
Guest Editor

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Published Papers (2 papers)

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16 pages, 2757 KiB  
Article
Towards the Generation of an ASFV-pA104R DISC Mutant and a Complementary Cell Line—A Potential Methodology for the Production of a Vaccine Candidate
by Ferdinando B. Freitas, Margarida Simões, Gonçalo Frouco, Carlos Martins and Fernando Ferreira
Vaccines 2019, 7(3), 68; https://doi.org/10.3390/vaccines7030068 - 18 Jul 2019
Cited by 14 | Viewed by 5314
Abstract
African swine fever (ASF) is a fatal viral disease of domestic swine and wild boar, considered one of the main threats for global pig husbandry. Despite enormous efforts, to date, neither the classical vaccine formulations nor the use of protein subunits proved to [...] Read more.
African swine fever (ASF) is a fatal viral disease of domestic swine and wild boar, considered one of the main threats for global pig husbandry. Despite enormous efforts, to date, neither the classical vaccine formulations nor the use of protein subunits proved to be efficient to prevent this disease. Under this scenario, new strategies have been proposed including the development of disabled infectious single cycle (DISC) or replication-defective mutants as potential immunizing agents against the ASF virus (ASFV). In this study, we describe the methodology to generate an ASFV-DISC mutant by homologous recombination, lacking the A104R gene, which was replaced by the selection marker (GUS gene). The recombinant viruses were identified when the infected cells acquired a blue color in the presence of X-Gluc (100 µg/mL), which is the substrate for the GUS gene. Since these viral particles result from loss-of-function mutations, being unable to replicate, helper-cell lines expressing the viral pA104R protein were produced. Vero and COS-1 cell lines were transfected by different methods, both physical and chemical, in order to stably express the ASFV-pA104R. Best results were obtained by using Lipofectamine 2000 and Nucleofection methodology of Vero with the pIRESneo vector and by using Flp-FRT site-directed recombination technology system in Flp-In CV-1 cells (transformed COS-1 cells with a single integration site in a transcriptional active region). In order to ensure an efficient and stable integration of the viral ORF on the host cellular genome, the maintenance of the insert was verified by PCR and its expression by immunofluorescence and immunoblot analysis. Although the isolation of the recombinant virus was not achieved, the confirmation of ASFV-ΔA104R sequence, and the detection of the recombinant mutant through three passages, suggest that this approach is feasible and could be a potential strategy to generate safe and efficient DISC vaccine candidates. Full article
(This article belongs to the Special Issue Vaccines targeting African Swine Fever Virus)
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Review
Subunit Vaccine Approaches for African Swine Fever Virus
by Natasha N. Gaudreault and Juergen A. Richt
Vaccines 2019, 7(2), 56; https://doi.org/10.3390/vaccines7020056 - 25 Jun 2019
Cited by 95 | Viewed by 10791
Abstract
African swine fever virus (ASFV) is the cause of a highly fatal disease in swine, for which there is no available vaccine. The disease is highly contagious and poses a serious threat to the swine industry worldwide. Since its introduction to the Caucasus [...] Read more.
African swine fever virus (ASFV) is the cause of a highly fatal disease in swine, for which there is no available vaccine. The disease is highly contagious and poses a serious threat to the swine industry worldwide. Since its introduction to the Caucasus region in 2007, a highly virulent, genotype II strain of ASFV has continued to circulate and spread into Eastern Europe and Russia, and most recently into Western Europe, China, and various countries of Southeast Asia. This review summarizes various ASFV vaccine strategies that have been investigated, with focus on antigen-, DNA-, and virus vector-based vaccines. Known ASFV antigens and the determinants of protection against ASFV versus immunopathological enhancement of infection and disease are also discussed. Full article
(This article belongs to the Special Issue Vaccines targeting African Swine Fever Virus)
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