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.

Highlights

  • Long before the importation of domestic pigs (Sus scrofa) to Africa, African swine fever virus (ASFV) circulated between their natural reservoirs, Ornithodoros moubata complex ticks and African wild pigs, mostly warthogs (Phacochoerus africanus), without causing any apparent disease [1]

  • Most of these vaccines have been designed to target the genotype II ASFV strains currently circulating in Europe and Asia, where, so far, the virus seems to circulate without significant genetic changes [11]

  • Our results confirm live attenuated ASFV as tools to dissect the mechanisms involved in cross-protection, which is crucial for the future designing of vaccines for endemic areas with complex ASFV epidemiological situations

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Summary

Introduction

Long before the importation of domestic pigs (Sus scrofa) to Africa, African swine fever virus (ASFV) circulated between their natural reservoirs, Ornithodoros moubata complex ticks and African wild pigs, mostly warthogs (Phacochoerus africanus), without causing any apparent disease [1]. Arbitration of regulatory agencies will guarantee that only the safest LAVs reach the field Most of these vaccines have been designed to target the genotype II ASFV strains currently circulating in Europe and Asia, where, so far, the virus seems to circulate without significant genetic changes [11]. A similar picture has been described for the genotype I virus circulating in Sardinia since 1978 until today, most probably reflecting the fact that a single virus incursion has occurred during the entire endemic period [12] Agreeing with this hypothesis, the introduction of ASFV in the Iberian Peninsula in at least two different occasions could contribute to explain the multiple non cross-protective or heterologous ASFV strains described in this area during the endemic period [13], complicating vaccine designing. Our results confirm live attenuated ASFV as tools to dissect the mechanisms involved in cross-protection, which is crucial for the future designing of vaccines for endemic areas with complex ASFV epidemiological situations

Viruses and Cells
Animal Welfare
Experimental Approach
ASFV Quantification by Real-Time PCR
Antibody Detection by ELISA
T Cell-Specific Immune Response
Infection-Inhibition Assay
Statistical Analysis
Results and Discussion
B A 71 C D 2
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