Vaccines targeting African Swine Fever Virus

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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