African Swine Fever (ASF) is a highly infectious haemorrhagic disease which affects European domestic pigs and wild boars, causing huge economic losses in the affected countries. ASF is a disease which must be mandatorily reported to the World Organization for Animal Health (OIE) and is caused by the African Swine Fever Virus (ASFV), a large-sized, highly complex virus against which there is still no effective treatment or vaccine.
ASF reached Spain in 1957 and was not eradicated until 1995, while paved the way for the re-opening of the international markets to our pork products and the development of the sector. ASF is endemic to Africa and in 2007 it arrived again in Europe, specifically Georgia, through infected pork products from the African continent. Since ASF reached Europe, it has spread in an uncontrolled manner, affecting countries such as Russia, Lithuania, Latvia, Estonia and Poland. The situation is out of control and the need for a vaccine to fight it is becoming increasingly urgent.
Unlike what is currently occurring in Europe, where the virus circulates chiefly among domestic pigs and wild boars, the situation in Africa is much more complex. The European domestic pig is the only host susceptible to the disease in Africa and the virus remains active within an uncontrolled cycle of ferral pigs and ticks. Wild African swine may become infected for life without showing any signs of the disease, while it is the ticks of the Ornithodoros genus which are fundamental in the cycle, as they facilitate its transmission between wild swine and also the domestic pig. ASF is currently regarded as the most limiting risk factor to the sustained growth of the pork industry, which is undergoing clear expansion in many areas of the African continent, thereby contributing to increasing poverty in one of the areas of the planet which is already one of the hardest hit.
The team led by Dr. Fernando Rodríguez from IRTA-CReSA is conducting research to discover a vaccine to help to improve the current situation of this swine disease, which is generating huge economic losses in the countries affected by it. The 3+ level biosafety facilities (BSL-3+) at IRTA-CReSA provide for a safe environment in which to work with the virus, as well as to vaccinate and infect animals, as it is an infectious agent with work requirements which are particularly strict in terms of biosafety.
A prototype vaccine which is raising hopes
The work recently published in the Journal of Virology outlines the progress achieved during the doctoral thesis by Dr. Paula L. Monteagudo in the field of vaccines against ASF. The work was performed under the direction of Dr. Fernando Rodríguez at IRTA-CReSA and Dr. María Luisa Salas at the Severo Ochoa Centre for Molecular Biology in Madrid, in partnership with the Boehringer Ingelheim Veterinary Research Center GmbH & Co. KG, Hanover, Germany.
The article describes how an isolated virulent strain of the ASFV was modified in Badajoz in 1971 (BA71) by means of the specific elimination of a single gene, the viral hemagglutinin, transforming it into an attenuated virus (BA71∆CD2) which can be used to vaccinate and protect pigs on an experimental basis against the virulent strain from which it comes (parental virus) and other strains of the ASFV.
The fact that an attenuated virus provides protection against infection with the virus it comes from is not new and there are numerous works which achieve protection against these strains, which we call homologous. The innovative aspect of the work is that, using an appropriate dosage of the BA71∆CD2 attenuated virus, it has been possible to protect pigs with complete effectiveness against a coetaneous virus of the BA71, the E75 (Spain 1975), which is a non-homologous or heterologous virus.
As a result of this study, we also know that the protection provided depends on the dosage used and that the cross-protection achieved in vivo between the different strains is correlated with the ability of the BA71∆CD2 vaccinal candidate to induce T-CD8+ cells capable of recognizing both strains, BA71 and E75 in vitro.
With these positive results in hand, a proposal was made to go one step further and find out whether the BA71∆CD2 vaccinal candidate was able to protect animals against infection with the strain which is currently circulating in Europe, the so-called Georgia 2007/01. Phylogenetically speaking, this strain is far more distant from the BA71 than the E75 and even belongs to a different genotype. The results obtained in the experiment were impressive, as all the animals receiving the appropriate dosage of BA71∆CD2 survived infection with the highly virulent Georgia 2007/01 heterologous strain.
The results obtained go beyond being able to demonstrate protection against the Georgia 2007/01, against which other experimental prototypes are beginning to emerge; they open up the possibility of being able to provide protection against very different viruses with a single vaccine, an essential point if we bear in mind the endemic areas in which many different viruses circulate at the same time, such as many parts of sub-Saharan Africa.
The fact that BA71∆CD2 may occur within a stable cell line (COS-1) instead of in primary macrophages, as until now, creates potential for future commercial exploitation. On the one hand, the absence of hemagglutinin from the virus makes transmission of the BA71∆CD2 via ticks difficult, as this protein is a key factor for it, and, on the other, it enables us to distinguish the vaccinated animals from the infected ones by means of a simple hemagglutination and/or hemadsorption inhibition test.
Despite the positive results obtained, some of the vaccinated animals displayed certain transient levels of the virus in their blood and nasal secretions, preventing us from guaranteeing the complete innocuousness of the vaccine during mass vaccination campaigns in the field. Therefore, the main challenge now focuses on attempting to improve its biosafety and, at the same time, enhancing the diagnostic methods making it possible to differentiate the animals which have been vaccinated from those which have been infected naturally.
Reference article: Monteagudo PL, Lacasta A, López E, Bosch L, Collado J, Pina-Pedrero S, Correa-Fiz F, Accensi F, Navas MJ, Vidal E, Bustos MJ, Rodríguez JM, Gallei A, Nikolin V, Salas ML, Rodríguez F. 2017. BA71ΔCD2: A new recombinant live attenuated African swine fever virus with cross-protective capabilities. J Virol JVI.01058-17 (For downloading the PDF of the article)
Acknowledgements: These studies have been funded by the Ministry of Economy and Competitiveness (MINECO) as a result of the awarding of an FPI fellowship grant (Paula L. Monteagudo) and the following projects: AGL2013-48998-C2-1-R, AGL2013-48998-C2-2-R, AGL2016-78160-C2-1-R. And also by the additional funds received from the Boehringer Ingelheim Veterinary Research Center GmbH & Co. KG, Hanover, Germany¸ without which this work would not have been possible.