African swine fever (ASF) is an acute viral disease of domestic swine with mortality rates approaching 100%. Currently endemic in extensive regions of Eurasia, ASF is “out of Africa” forever, a situation that poses a grave threat to the US swine industry. While our current concern is ASFV Georgia-07, other emerging ASFV strains from African reservoirs threaten swine populations for the indefinite future. Economic analysis indicates an ASF outbreak in the U.S. would result in approximately $15 billion USD in losses, assuming the disease is rapidly controlled (1).
Despite the continual African swine fever (ASF) threat and the fact that the disease was first described over a century ago, it is surprising that no ASF vaccine is available. Current data indicate that ASF vaccines could indeed be developed, as pigs surviving ASFV infection develop long-term resistance to homologous virus challenge but rarely to heterologous virus challenge. Significant progress has been made on engineering attenuated ASF viruses as potential vaccines and promising vaccine candidates are available and at various stages of evaluation (2, 3). However, none have been properly examined for safety and efficacy under field conditions and none have been licensed for use in the US or Europe. Likely, a first-generation Georgia-07 vaccine will be a live-attenuated vaccine (LAV) and its availability will positively impact disease control in endemic regions. However, it is hard to imagine a scenario where they would be used in nonendemic countries with highly developed swine industries; issues of efficacy, residual pathogenicity with immunopathologic sequelae, and potential for long-term viral persistence raise significant questions about their suitability for use as an emergency response tool in the US (2). ASF outbreaks in China linked to use of unlicensed ASF gene-deleted vaccine viruses and the recent safety concerns raised following use of an ASF LAV in Vietnam highlight potential problems with ASF LAV vaccine use in the field (Reuters 1-21-2, Pig Progress 9-6-22 and multiple personal communications). Efforts to design and develop safe and efficacious DIVA-compatible subunit or vectored ASF vaccines suitable for use in the US are urgently needed.
To date, identification of ASFV protective antigens (PA), the viral proteins capable of stimulating immunity in the pig and the critical first step in developing a subunit vaccine, has proven challenging. The ASF virus (ASFV) is complex (>170 proteins), virus infection-biology is poorly understood and, in most cases, the experimental strategies used to identify ASFV PA have employed unfocused “discovery-based” approaches. In the work described here, we have used comparative ASF genomic analysis together with a novel inter-serogroup ASFV chimeric virus strategy and vaccination challenge experiments in pigs to identify ASFV PA.
The ASFV chimeric virus approach successfully identified four putative serotype-associated PA (CD2v (pEP402R), C-type lectin (EP153R) and ASF locus tags: 789 and 289). Protection observed in protected animals was solid; only transient fever/clinical responses were observed accompanied by significantly delayed and markedly reduced viremias of approximately 100 to1000-fold (Fig. 4, Burmakina and Khatiwada et al., unpublished data). One or possibly two additional putative viral PA likely will be identified from ongoing studies and improved overall protection results for vaccinated animals may result.
This work provides critical foundational information regarding potential ASFV PA necessary for design/development of safe and efficacious DIVA compatible subunit or vectored ASF vaccines that would be of considerable value for use in the US should ASF be introduced.
- A novel inter-serogroup ASFV chimeric virus strategy and vaccination challenge experiments in pigs proved successful for identifying putative ASFV PA
- Immunization with four ASFV serotype-associated PA, (CD2v (pEP402R), C-type lectin (EP153R) and ASF locus tags: 789 and 289) protected animals following ASFV challenge.
- Identified ASFV PA should be further evaluated as components of DIVA-compatible subunit or vectored ASF vaccines.