African swine fever (ASF) is a highly infectious hemorrhagic disease of compulsory declaration to the World Animal Health (OIE) and causes important economical losses in affected countries. The causative agent of the disease is African swine fever virus (ASFV), a large and complex virus against which there is no effective vaccine available and therefore, its control and eradication relies on the rapid diagnostic of the disease and culling of infected and/or exposed animals to the virus. ASF remains endemic in sub-‐Saharan Africa where the virus is in a sylvatic cycle between wild pigs and ticks, occasionally infecting highly susceptible domestic pigs. The virus re-‐entered Continental Europe in 2007 and since then, the virus has circulated from Georgia to the rest of the Caucasian Regions, Russia and more recently has entered the European Union borders. The main objective of this Thesis was developing a new vaccine strategy against ASF, based on the genetic manipulation of the ASFV genome. The main findings obtained can be summarized as follows: i) the deletion of the hemagglutinin gene or viral CD2, strongly attenuated the ASFV-‐BA71 virulent strain in vivo; ii) BA71.ΔCD2, a live attenuated virus defective for CD2v, is able to confer in vivo protection in a dose-‐dependent manner against the lethal challenge with either the homologous BA71 virus or the heterologous E75 virus; iii) Inoculation with the higher dose tested of BA71.ΔCD2, 106 PFU, conferred complete protection against BA71 and E75; iv) the cross-‐protection induced by BA71.ΔCD2 correlated with its ability to induce specific CD8+ T-‐cells capable to in vitro recognize both BA71 and E75 viruses; an effect observed for the first time for ASFV-‐attenuated viruses, capable only to confer protection against homologous viruses; v) Inoculation of 106 PFU of BA71.ΔCD2 protected 100% of the immunized pigs against lethal challenge with the virulent strain Georgia07, currently circulating in Europe. The encouraging results obtained during this Thesis open new expectations and strength our opinion about the possibility of obtaining a vaccine against ASFV. Despite these promising findings, this vaccine prototype should be refined to obtain a safer vaccine capable also of inducing a differential immune response from circulating ASF viruses; a must in Veterinary vaccines against diseases of compulsory declarations.
- Attenuated vacine