African Swine Fever Vaccines: Current Progress and Future Challenges

Despite significant advances in understanding African swine fever virus (ASFV), developing an effective vaccine remains one of the greatest challenges in controlling the disease. The virus possesses a large and complex genome, encodes numerous immune escape proteins, and interferes with host immune responses, making vaccine development particularly difficult¹. Although considerable progress has been made with several vaccine platforms, preventive vaccination is still unavailable in many parts of the world, and inactivated ASFV vaccines remain prohibited in the European Union and several other countries because they fail to provide effective protection^2,3. 

For practicing veterinarians, understanding the current status of ASF vaccine development is important for appreciating both the progress achieved and the limitations that continue to influence disease control strategies. 

Why Developing an ASF Vaccine Is So Challenging 

ASFV has evolved multiple mechanisms that allow it to evade host immunity while promoting its own replication. The virus regulates host cell protein expression and suppresses innate immune responses, creating conditions that favor persistent viral survival¹. These characteristics complicate the identification of protective antigens capable of inducing reliable immunity. 

Protective immunity has been achieved with attenuated vaccine candidates, but several important challenges remain. Differences in viral virulence, antigen diversity, viral phenotype, and the limited cross-protective immunity between different ASFV strains continue to restrict the development of broadly protective live attenuated vaccines³. 

Live Attenuated Vaccines Show the Greatest Promise 

Current vaccine development has largely focused on live attenuated viruses generated through targeted deletion of virulence-associated genes. Gene-deficient vaccine candidates have been developed by removing genes such as 9GL (B119L), UK (DP96R), CD2v (EP402R), DP148R, and several members of the multigene family (MGF)^3,4. These modified viruses have demonstrated protective effects in immunized animals while exhibiting reduced virulence⁵. 

Additional vaccine candidates have been produced by deleting other virulence-associated genes. For example, deletion of the A137R gene resulted in a completely attenuated virus that demonstrated potential as a live attenuated vaccine against the epidemiologically important Georgia isolate³. However, deletion of the same genes in genotype VIII strains did not produce similar attenuation, highlighting the influence of the viral genetic background on vaccine performance³. 

A live attenuated vaccine candidate containing seven gene deletions also demonstrated dose-dependent protection. Higher immunization doses provided longer-lasting protection, whereas two medium-dose vaccinations failed to provide complete protection 80 days after the final immunization⁶. 

Emerging Vaccine Strategies 

Beyond live attenuated vaccines, several genetically engineered vaccine platforms continue to be explored. Multiple ASFV proteins, including p30, p54, p72, CD2v, EP153R, p12, D117L, and pp62, have been evaluated as potential protective antigens either individually or in combination⁷. 

Subunit vaccines offer important safety advantages compared with live attenuated vaccines. Various antigen combinations have successfully induced antigen-specific antibodies, IFN-γ-producing cells, and cytotoxic T lymphocyte responses, although currently available subunit vaccines have not achieved complete protection against ASFV^7,8. 

Large antigen cocktail vaccines have also been investigated using adenovirus-vectored ASFV antigens. While these approaches have expanded understanding of protective immune responses, complete and consistent protection has not yet been achieved under all conditions⁴. 

Remaining Challenges for Future Vaccine Development 

Although live attenuated vaccines currently represent the most promising strategy for ASF prevention, their practical application requires careful evaluation. Safety concerns, including possible reversion to virulence, adverse reactions, and persistent infection, must be thoroughly addressed before widespread field use^3,7. 

One live attenuated vaccine candidate, ASFV-G-∆I177L, has demonstrated effective protection against both the parental Georgia 2007 strain and a virulent Vietnamese isolate. It has also shown genetic stability, maintained its attenuated phenotype during serial passage, and demonstrated favorable safety characteristics, including minimal virus shedding and transmission under different conditions^3,9. 

Continued progress will depend on improved understanding of ASFV structure, identification of protective antigens and immune mechanisms, development of genetically stable vaccine strains, and establishment of suitable cell culture systems that reduce the cost and complexity of vaccine production^1,7. 

Conclusion 

Considerable progress has been made in African swine fever vaccine development, particularly through live attenuated and genetically engineered vaccine platforms. Nevertheless, the complexity of ASFV biology, strain diversity, immune evasion, and safety considerations continue to present major obstacles to the development of a universally protective vaccine. Until these challenges are overcome, rigorous biosecurity and early disease detection remain essential components of African swine fever control while vaccine research continues to advance. 

References 

1. Bosch-Camós L, López E, Rodriguez F. African swine fever vaccines: a promising work still in progress. Porcine health management. 2020 Jul 2;6(1):17. https://link.springer.com/content/pdf/10.1186/s40813-020-00154-2.pdf 

2. Blome S, Franzke K, Beer M. African swine fever–A review of current knowledge. Virus research. 2020 Oct 2;287:198099. https://www.sciencedirect.com/science/article/pii/S0168170220304019 

3. Li Z, Chen W, Qiu Z, Li Y, Fan J, Wu K, Li X, Zhao M, Ding H, Fan S, Chen J. African swine fever virus: a review. Life. 2022 Aug 17;12(8):1255. https://www.mdpi.com/2075-1729/12/8/1255 

4. Cadenas-Fernández E, Sánchez-Vizcaíno JM, Kosowska A, Rivera B, Mayoral-Alegre F, Rodríguez-Bertos A, Yao J, Bray J, Lokhandwala S, Mwangi W, Barasona JA. Adenovirus-vectored African swine fever virus antigens cocktail is not protective against virulent Arm07 isolate in Eurasian wild boar. Pathogens. 2020 Feb 28;9(3):171. https://www.mdpi.com/2076-0817/9/3/171 

5. Bhattacharya D, Teramo A, Gasparini VR, Huuhtanen J, Kim D, Theodoropoulos J, Schiavoni G, Barilà G, Vicenzetto C, Calabretto G, Facco M. Identification of novel STAT5B mutations and characterization of TCRβ signatures in CD4+ T-cell large granular lymphocyte leukemia. Blood cancer journal. 2022 Feb 24;12(2):31. https://www.nature.com/articles/s41408-022-00630-8.pdf 

6. Chen W, Zhao D, He X, Liu R, Wang Z, Zhang X, Li F, Shan D, Chen H, Zhang J, Wang L. A seven-gene-deleted African swine fever virus is safe and effective as a live attenuated vaccine in pigs. Science China Life Sciences. 2020 May;63(5):623-34. https://link.springer.com/content/pdf/10.1007/s11427-020-1657-9.pdf 

7. Wu K, Liu J, Wang L, Fan S, Li Z, Li Y, Yi L, Ding H, Zhao M, Chen J. Current state of global African swine fever vaccine development under the prevalence and transmission of ASF in China. Vaccines. 2020 Sep 15;8(3):531. https://www.mdpi.com/2076-393X/8/3/531 

8. Davies K, Goatley LC, Guinat C, Netherton CL, Gubbins S, Dixon LK, Reis AL. Survival of African swine fever virus in excretions from pigs experimentally infected with the Georgia 2007/1 isolate. Transboundary and emerging diseases. 2017 Apr;64(2):425-31. https://onlinelibrary.wiley.com/doi/pdf/10.1111/tbed.12381 

9. Tran XH, Phuong LT, Huy NQ, Thuy DT, Nguyen VD, Quang PH, Ngôn QV, Rai A, Gay CG, Gladue DP, Borca MV. Evaluation of the safety profile of the ASFV vaccine candidate ASFV-G-ΔI177L. Viruses. 2022 Apr 25;14(5):896. https://www.mdpi.com/1999-4915/14/5/896