Live Attenuated African Swine Fever Viruses as Ideal Tools to Dissect the Mechanisms Involved in Cross-Protection

Abstract

African swine fever (ASF) has become the major threat for the global swine industry. Furthermore, the epidemiological situation of African swine fever virus (ASFV) in some endemic regions of Sub-Saharan Africa is worse than ever, with multiple virus strains and genotypes currently circulating in a given area. Despite the recent advances on ASF vaccine development, there are no commercial vaccines yet, and most of the promising vaccine prototypes available today have been specifically designed to fight the genotype II strains currently circulating in Europe, Asia, and Oceania. Previous results from our laboratory have demonstrated the ability of BA71∆CD2, a recombinant LAV lacking CD2v, to confer protection against homologous (BA71) and heterologous genotype I (E75) and genotype II (Georgia2007/01) ASFV strains, both belonging to same clade (clade C). Here, we extend these results using BA71∆CD2 as a tool trying to understand ASFV cross-protection, using phylogenetically distant ASFV strains. We first observed that five out of six (83.3%) of the pigs immunized once with 106 PFU of BA71∆CD2 survived the tick-bite challenge using Ornithodoros sp. soft ticks naturally infected with RSA/11/2017 strain (genotype XIX, clade D). Second, only two out of six (33.3%) survived the challenge with Ken06.Bus (genotype IX, clade A), which is phylogenetically more distant to BA71∆CD2 than the RSA/11/2017 strain. On the other hand, homologous prime-boosting with BA71∆CD2 only improved the survival rate to 50% after Ken06.Bus challenge, all suffering mild ASF-compatible clinical signs, while 100% of the pigs immunized with BA71∆CD2 and boosted with the parental BA71 virulent strain survived the lethal challenge with Ken06.Bus, without almost no clinical signs of the disease. Our results confirm that cross-protection is a multifactorial phenomenon that not only depends on sequence similarity. We believe that understanding this complex phenomenon will be useful for designing future vaccines for ASF-endemic areas.

The first genotype II African swine fever virus isolated in Africa provides insight into the current Eurasian pandemic

“…On an applied note, the observation of molecular divergence between Tanzania/Rukwa/2017/1 and Georgia 2007/1, together with the viruses recently derived from the latter, suggests that live attenuated vaccines derived from Georgia/2007/1 may not always cross-protect against ASFV genotypes derived from different regions of Africa, as it has been observed for phylogenetically distant ASFV strains within the ASFV p72 genotypes 46 .…”

African Swine Fever Virus Ubiquitin-Conjugating Enzyme Is an Immunomodulator Targeting NF-κB Activation

“…ASFV is a swine virus for which no vaccine has been approved yet. The development of attenuated vaccines in which specific immunomodulators are removed is a promising approach [ 15 , 16 ]. Work with other large DNA viruses has demonstrated that the removal of NF-κB inhibitors enhances the development of effector and memory T cell responses, and provides safer and yet more immunogenic vaccine vectors [ 46 , 47 , 48 ], although multiple deletions have been shown to reduce immunogenicity [ 49 ].…”

“…ASFV produces a deadly infection of swine that is spreading in three continents (Asia, Europe and Africa) with high economic burden. At present, there is not a commercial vaccine available, although live attenuated vaccines are being developed by deletion of genes related to the viral manipulation of the immune system [ 15 , 16 ]. Hence, a better understanding of how ASFV evades host immune responses has the potential to impact in the rational design of these vaccines.…”

M448R and MGF505-7R: Two African Swine Fever Virus Antigens Commonly Recognized by ASFV-Specific T-Cells and with Protective Potential

“…Even though most of the times protection is limited to homologous protection [ 13 , 16 , 17 ], LAVs have become essential tools to confirm the protective role of innate [ 35 , 36 , 37 , 38 ] and adaptive immune responses, with both humoral response [ 39 , 40 , 41 ] and ASFV-specific CD8 + T-cells [ 21 ] playing crucial roles in protection. In this regard, recombinant LAVs are the most advanced candidates against the pandemic virus [ 14 , 15 , 16 , 17 ]. Although still pending approval from the authorized governmental agencies, LAVs candidates should contribute in the near future to control ASF in endemic areas and in emergencies.…”

“…As described in the latest blueprint published by the European Commission, live attenuated viruses (LAVs) are the most plausible ASF-vaccine option in the short term [ 10 ]. The only data indicating protection from challenge infection available today against the pandemic ASFV strain, currently circulating in Asia and Europe, come from the use of naturally attenuated virus strains [ 11 , 12 ] or recombinant LAVs [ 13 , 14 , 15 , 16 , 17 , 18 ]. Despite their protective abilities, LAVs have to improve their safety and DIVA capabilities to be commercially viable in ASF-free areas.…”