Lessons learned from using African swine fever Attenuated viruses

Lack of vaccines available against African swine fever (ASF) difficult even more the control of this important swine disease. The great complexity of ASF virus (ASFV) together with the lack of knowledge about the mechanisms involved in protection partially explains this absence. Our research group, in collaboration with Researchers from the University of Córdoba (UCO) and from the CBMSO-CSIC (Madrid), intended to share some light over this complex reality with this work, part of the PhD of Anna Lacasta and more recently published in Veterinary Research (Lacasta et al., Vet Res. 2015;46(1):135). 

In this work were compared the in vivo infection kinetics of two homologous ASFV strains: the highly virulent E75 and its attenuated counterpart E75CV1, fruit of the adaptation of E75 to grow in the CV1 cell line (*).

Concomitantly, the induction of the immune responses induced by these viruses thorough the time was also followed. The strength and the main novelty of this work resides in the fact that all the analysis were performed using porcine lymphoid tissues, target site for ASFV in vivo infection, instead of using porcine macrophages grown in vitro. The fact that only 4 blind passages separate the virus pair used also facilitated he validation of the main conclusions obtained, next numbered:

i) Live and death after ASFV infection depends on many factors including the pathogenicity of the ASFV strain, the dose of virus received and very importantly, the host ability to mount an effective innate immune response immediately after the infection. Thus, the highly virulent E75 strain was capable to efficiently evade this first immune system recognition as shown with the lack of activation of immune mediators at day 1 post-infection (pi). In clear contrast, same dose of the attenuated E75CV1 efficiently activated the innate immunity, triggering the activation of many different immune mediators and immune pathways at this same time pi

ii) The mechanisms of immune evasion used by E75 facilitated the replication of the virus and the systemic infection, ending with a massive tissue destruction and a cytokine storm detectable by day 7pi both in tissues and in vital fluids, coinciding with the death of the animals. In clear contrast, the innate immune response mounted in response to E75CV1 infection limited the virus replication, ameliorated the infection and also contributed to the induction of protective adaptative memory responses. Thus, E75CV1-surviving pigs remained solidly protected against homologous E75 Virulent challenge but conversely succumbed to BA71 heterologous ASFV challenge. This, together with the lack of safety of live attenuated vaccines, is the main handicap hampering their use in the field. 

iii) The differential protection observed against E75 and BA71 correlated with the presence in E75CV1 surviving animals of CD8+T-cells capable to exclusively proliferate in response to in vitro stimulation with the homologous E75 ASFV-strain but never in response to BA71.

Independently of its academic nature, the lesson learned allowed re-orienting our research towards the development of vaccines prototypes inducing CD8+ T-cells capable to recognize very different ASFV strains (heterologous viruses). Once more, we are learning from the enemy.

*The attenuated ASFV strain E75CV1 and many other reagents and knowledge today used in the ASFV field was obtained by Dr. Francisco Ruiz-Gonzalvo (Paco), an INIA Researcher that unfortunately passed away few years ago. Many of us learned a lot from him and enjoyed his friendship. We will miss him forever.

 

 

 

 

To contact Dr. Rodriguez:

Dr. Fernando Rodríguez González
Investigador de l’IRTA del programa de Sanitat Animal al CReSA
Email: fernando.rodriguez@irta.cat
Telèfon: +34 93 467 40 40
Campus UAB, Edifici CReSA s/n,  08193  Bellaterra (Cerdanyola del Vallès) Spain

Link:

Article written here can be found at the following link:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654842/pdf/13567_2015_Article_275.pdf

REF. PROJECT:

This work was made possible thanks to funding of the research project entitled: STRATEGIES FOR PROTECTION AGAINST African swine fever: BASIC RESEARCH IN PROTOTYPE VACCINE (AGL2013-48998-C2-1-R) of the Ministry of Economy and Competitiveness (Spain)

About IRTA:

IRTA is a research institute devoted to R+D+I in a variety of agri-food areas, such as vegetal production, animal production, food industries, environment and global change, and agri-food economy. The transfer of scientific advances contribute to the modernization, competitiveness and sustainable development of agriculture, food and aquaculture sectors, the supply of healthy and quality foods for consumers and, consequently, improving the welfare of the population. IRTA is assigned to the Departament d’Agricultura, Ramaderia, Pesca, Alimentació i Medi Natural (DAAM, Department of Agriculture) of the Generalitat de Catalunya (Government of Catalonia).

cid:image002.jpg@01D05037.D5E89FC0  cid:image004.jpg@01D05037.D5E89FC0  cid:image006.jpg@01D05037.D5E89FC0  cid:image008.jpg@01D05037.D5E89FC0 irtaldia

¡Recommend this page!: