Next Article in Journal
Shedding Light on Novel Pathogenic and Therapeutic Aspects Related to Immune-Mediated Skin Diseases
Next Article in Special Issue
Involvement of the MGF 110-11L Gene in the African Swine Fever Replication and Virulence
Previous Article in Journal
Influenza, Pneumococcal and Herpes Zoster Vaccination Rates in Patients with Autoimmune Inflammatory Rheumatic Diseases
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Opinion

Summary of the Current Status of African Swine Fever Vaccine Development in China

1
China Animal Health and Epidemiology Center, No. 369 Nanjing Road, Qingdao 266032, China
2
Key Laboratory of Animal Biosafety Risk Prevention and Control (South), Ministry of Agriculture and Rural Affairs of the People’s Republic of China, No. 369 Nanjing Road, Qingdao 266032, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Vaccines 2023, 11(4), 762; https://doi.org/10.3390/vaccines11040762
Submission received: 2 February 2023 / Revised: 24 March 2023 / Accepted: 27 March 2023 / Published: 29 March 2023
(This article belongs to the Special Issue Diagnosis and Control of African Swine Fever Virus (ASFV) Infection)

Abstract

:
African swine fever (ASF) is a highly lethal and contagious disease of domestic pigs and wild boars. There is still no credible commercially available vaccine. The only existing one, issued in Vietnam, is actually used in limited quantities in limited areas, for large-scale clinical evaluation. ASF virus is a large complex virus, not inducing full neutralizing antibodies, with multiple genotypes and a lack of comprehensive research on virus infection and immunity. Since it was first reported in China in August 2018, ASF has spread rapidly across the country. To prevent, control, further purify and eradicate ASF, joint scientific and technological research on ASF vaccines has been carried out in China. In the past 4 years (2018–2022), several groups in China have been funded for the research and development of various types of ASF vaccines, achieving marked progress and reaching certain milestones. Here, we have provided a comprehensive and systematic summary of all of the relevant data regarding the current status of the development of ASF vaccines in China to provide a reference for further progress worldwide. At present, the further clinical application of the ASF vaccine still needs a lot of tests and research accumulation.

1. Introduction

African swine fever (ASF) is an acute, febrile, highly contagious disease of pigs caused by the infection with African swine fever virus (ASFV). ASF is on the list of notifiable diseases of the World Organization for Animal Health (WOAH) and is classified as a Class I animal disease in the Chinese list of animal pathogenic microorganisms, which refers to diseases that pose a serious threat to humans and animals and require urgent, severe and compulsory measures for their prevention, control and eradication. ASFV can be transmitted over long distances through pork products, swill and other items, which has set the precedent for transcontinental outbreaks. In 2018, ASF appeared suddenly in China and the development of the African swine fever vaccine was initiated [1,2]. In the past 4 years (2018–2022), several groups in China have presided over/participated in the research and development of various types of ASF vaccines. More than 50 vaccine-related articles have been published (Figure 1), with some studies making marked progress and reaching certain milestones. To provide a reference for further progress worldwide, we have provided a comprehensive and systematic summary of all of the relevant data regarding the current status of the development of ASF vaccines in China.

2. Gene-Deleted Live Attenuated Vaccines (LAVs)

After ASF was first reported in China in 2018, the outbreak strains designated in China were 2018/1 [2], pig/HLJ/18 [3] and SY18 [1] and these were isolated by different research groups and used to conduct relevant vaccine studies. Foreign experience in ASF vaccine research has shown that inactivated vaccines have no reliable protection [4]; cell-passage-attenuated vaccine candidates is relatively difficult to determine the appropriate number of passages [5]; natural attenuated vaccine candidates are rare [6,7,8]; subunit vaccines/or vector vaccines have weak and unstable protection, etc.; so, these vaccine development methods are limited by a degree of uncertainty. In recent years, with the continuous development of gene editing technologies, artificial gene-deleted LAVs have become the most promising strategy for ASF vaccine development [9].
Among them, the MGF 360/505 gene (six genes) and CD2v gene have received wide attention from researchers. MGF360 and MGF505, located in the highly variable left terminal genomic region of ASFV, encode products with common structural similarities [10,11,12]. It was shown that MGF360 and MGF505 genes are involved in the inhibition of interferon (IFN) production [13] and are associated with viral virulence. The deletion of these genes can lead to the reduced virulence of ASFV and to the acquisition of gene-deleted live attenuated vaccines [14,15]. CD2v (EP402R) is an ASFV protein with a sequence homologous to the T lymphocyte surface adhesion receptor CD2, detected in the outer layer of the budding virus [16]. The extracellular structural domain causes the hemadsorption phenomenon [17]. The deletion of the CD2v (EP402R) gene highly attenuates the virulence of ASFV in vivo [14]. In China, several independent research groups have conducted knock-out studies on the major genes of ASFV, and three of them have selected the combination of the deleted MGF 360/505 gene (six genes) and CD2v gene (one gene) as vaccine candidate strains for further evaluation [18,19].

2.1. Progress of Seven-Gene-(Dual-Gene)-Deleted LAV Research

Research on the HLJ/18-7GD strain has been highly comprehensive and has achieved the most rapid progress (see Table 1 for details). This gene-deleted live attenuated vaccine is based on the ASFV HLJ/18 virus as the backbone with the deletion of seven genes encoding MGF5051R, MGF505-2R, MGF505-3R, MGF360-12L, MGF36013L, MGF360-14L and CD2v. Safety evaluation and protective efficacy studies conducted on more than 1100 specific pathogen-free (SPF) pigs in the laboratory, as well as experiments on 14,487 commercial fattening pigs and 229 breeding sows in the field, have confirmed that the HLJ/18-7GD strain is genetically stable, does not cause disease or become virulent after inoculation and has no adverse effects on the growth, weight gain or mortality of fattening pigs. The survival protection rate for commercial pigs in the field exceeds 80% [19]. Other seven-gene-deleted strains, such as the ASFV CN2018 ΔMGF/ΔCD2v strain (unpublished data) and ASFV SY18 ΔMGF/ΔCD2v [20], have also had animal experiments conducted and have improved to be safe and effective. However, although the three strains have similar deletion genes, the specific knockout sites are not identical, which, together with the differences in purification processes, culture systems and the number of passages, may lead to some differences in the deletion strains and the related test data.
As with ASFV-G-ΔI177L [21] (US vaccine strain), Lv17/WB/Rie1 [7] (European boar oral vaccine strain) and FK-32/13 [22] (Russian cell passage vaccine strain), HLJ/18-7GD [18] (Chinese vaccine strain) is still in the stage of clinical evaluation. The government has concerns about the safety of attenuated vaccines, the occurrence of post-viral shedding and post-vaccination complications and the inadequate protection of immunocompromised pigs [23], and is cautious about the large-scale promotion of an attenuated vaccine.

2.2. Research Progress of Other Gene-Deleted LAVs

During the clinical evaluation of the seven-gene-deleted live attenuated strains, research on gene-deleted live attenuated strains of ASF in China has not stopped, with increasing numbers of participating units and continuous updates of research results (Table 2). In addition to the above-mentioned seven-gene-deleted live attenuated strains, other ASFV gene-deleted strains have been constructed in recent years. Genes that can be knocked out include those related to innate immunity, such as MGF100-1R [24], MGF 110-9L [25], MGF 505-2R [26], MGF 505-7R(A528R) [27,28,29], QP509L/QP383R [30], E120R [31], F317 [32] and L7L-L11L [33], genes related to virus transcription, such as MGF360-9L [34], I226R [35], I215L [36,37] and I267 [38], and genes related to virus structure, such as A137R [39]. Strains with deletions of these genes or their combination with previously reported genes may provide new candidates for vaccine evaluation similar to the ASFV-Δ9L/Δ7R strain with the deletion of both MGF360-9L and MGF505-7R genes [40], and the ASFV-GZΔI177LΔCD2vΔMGF with simultaneous deletion of I177L, CD2v and virulence-associated MGF360-12L-MGF360-14L gene clusters [41]. Evaluations of most of the above vaccine candidates are currently limited to small-scale animal experiments (5–10 animals) in the laboratory, mainly to meet publication/patent requirements, and have not yet been studied on a large scale.

3. Other Vaccines

The design and production of subunit or live vector vaccines do not involve the manipulation of the ASF live virus, and challenge protection data are not necessary in the submission content of patent applications. This has led to the emergence of a large number of ASF vaccine patents in China and as of December 2022, the number of ASF subunit and live vector vaccine patents publicly reported in China has reached 69 and 43, respectively, exceeding the number of patents for genetically attenuated live vaccines.
Based on previous experience in animal disease vaccine design and improved understanding based on previous research on the ASF subunit and live vector vaccines, Chinese researchers have adopted similar research strategies for the development of the ASF vaccine (Figure 2). For the subunit vaccine, the protein sequences were analyzed using bioinformatics methods [44,45,46,47] or by using monoclonal antibodies [48] to screen the antigenic epitopes. Once identified, the ASFV antigenic proteins were combined with other bacterial/viral proteins or functional proteins [49,50], so that the expressed ASFV antigenic proteins could self-assemble into a certain structure or improve the expression efficiency to improve the immunogenicity of the ASFV proteins. For the live vector vaccines, different vectors [51,52,53,54,55] and multiple gene expressions [56,57,58] were also evaluated.
However, the major challenges to the development of the ASF subunit or live vector vaccines in China remain, with most of the candidates awaiting protective immunity validation and patent authorization. Some patents relate only to the design concept of combining different genes without an in-depth discussion; so, it is impossible to judge their vaccine application potential.

4. Conclusions

Several ASF vaccines, all LAVs, that have entered the clinical trial phase have been urgently suspended due to safety concerns. ASF subunit vaccines are not associated with risks such as recombination, virulence reversion or virulence residues, and have unparalleled advantages in safety compared with LAVs; therefore, ASF subunit vaccines are now a focus of current research. However, further technological advances and basic research are required to successfully develop a safe and effective ASF vaccine.

Author Contributions

Conceptualization, N.H., H.Q. and T.X., investigation, N.H.; data curation, H.Q. and T.X.; writing—original draft preparation, N.H.; writing—review and editing, H.Q. and T.X.; visualization, Y.H. and Y.Z.; project administration, S.G.; funding acquisition, S.G. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the National Project for the Prevention and Control of major exotic animal diseases (grant no. 2022YFD1800500), and the National Key R&D Program for the 14th Five-Year Plan, the Ministry of Science and Technology, China.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

The authors gratefully thank Zhiliang Wang, the expert of the WOAH reference laboratory for African swine fever, for the revision of parts of the article.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Zhou, X.; Li, N.; Luo, Y.; Liu, Y.; Miao, F.; Chen, T.; Zhang, S.; Cao, P.; Li, X.; Tian, K.; et al. Emergence of African Swine Fever in China, 2018. Transbound. Emerg. Dis. 2018, 65, 1482–1484. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  2. Ge, S.; Li, J.; Fan, X.; Liu, F.; Li, L.; Wang, Q.; Ren, W.; Bao, J.; Liu, C.; Wang, H.; et al. Molecular Characterization of African Swine Fever Virus, China, 2018. Emerg. Infect. Dis. 2018, 24, 2131–2133. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Zhao, D.; Liu, R.; Zhang, X.; Li, F.; Wang, J.; Zhang, J.; Liu, X.; Wang, L.; Zhang, J.; Wu, X.; et al. Replication and virulence in pigs of the first African swine fever virus isolated in China. Emerg. Microbes Infect. 2019, 8, 438–447. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  4. Urbano, A.C.; Ferreira, F. African swine fever control and prevention: An update on vaccine development. Emerg. Microbes Infect. 2022, 11, 2021–2033. [Google Scholar] [CrossRef]
  5. Manso Ribeiro, J.; Nunes Petisca, J.L.; Lopes Frazao, F.; Sobral, M. Vaccination contre la peste porcine africaine. Bull. De L’office Int. Des Epizoot. 1963, 60, 921–937. [Google Scholar]
  6. Boinas, F.S.; Hutchings, G.H.; Dixon, L.K.; Wilkinson, P.J. Characterization of pathogenic and non-pathogenic African swine fever virus isolates from Ornithodoros erraticus inhabiting pig premises in Portugal. J. Gen. Virol. 2004, 85, 2177–2187. [Google Scholar] [CrossRef]
  7. Gallardo, C.; Soler, A.; Rodze, I.; Nieto, R.; Cano-Gómez, C.; Fernandez-Pinero, J.; Arias, M. Attenuated and non-haemadsorbing (non-HAD) genotype II African swine fever virus (ASFV) isolated in Europe, Latvia 2017. Transbound. Emerg. Dis. 2019, 66, 1399–1404. [Google Scholar] [CrossRef]
  8. Sun, E.; Huang, L.; Zhang, X.; Zhang, J.; Shen, D.; Zhang, Z.; Wang, Z.; Huo, H.; Wang, W.; Huangfu, H.; et al. Genotype I African swine fever viruses emerged in domestic pigs in China and caused chronic infection. Emerg. Microbes Infect. 2021, 10, 2183–2193. [Google Scholar] [CrossRef]
  9. Rock, D.L. Thoughts on African Swine Fever Vaccines. Viruses 2021, 13, 943. [Google Scholar] [CrossRef]
  10. Gonzalez, A.; Calvo, V.; Almazan, F.; Almendral, J.M.; Ramirez, J.C.; Delavega, I.; Blasco, R.; Vinuela, E. MULTIGENE FAMILIES IN AFRICAN SWINE FEVER VIRUS-FAMILY-360. J. Virol. 1990, 64, 2073–2081. [Google Scholar] [CrossRef] [Green Version]
  11. Rodriguez, J.M.; Yanez, R.J.; Pan, R.; Rodriguez, J.F.; Salas, M.L.; Vinuela, E. Multigene Families In African Swine Fever Virus-Family-505. J. Virol. 1994, 68, 2746–2751. [Google Scholar] [CrossRef] [Green Version]
  12. Yozawa, T.; Kutish, G.F.; Afonso, C.L.; Lu, Z.; Rock, D.L. 2 Novel Multigene Families, 530 And 300, In The Terminal Variable Regions Of African-Swine-Fever Virus Genome. Virology 1994, 202, 997–1002. [Google Scholar] [CrossRef]
  13. Afonso, C.L.; Piccone, M.E.; Zaffuto, K.M.; Neilan, J.; Kutish, G.F.; Lu, Z.; Balinsky, C.A.; Gibb, T.R.; Bean, T.J.; Zsak, L.; et al. African swine fever virus multigene family 360 and 530 genes affect host interferon response. J. Virol. 2004, 78, 1858–1864. [Google Scholar] [CrossRef] [Green Version]
  14. Monteagudo, P.L.; Lacasta, A.; Lopez, E.; Bosch, L.; Collado, J.; Pina-Pedrero, S.; Correa-Fiz, F.; Accensi, F.; Navas, M.J.; Vidal, E.; et al. BA71DeltaCD2: A New Recombinant Live Attenuated African Swine Fever Virus with Cross-Protective Capabilities. J. Virol. 2017, 91, e01058-17. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  15. O’Donnell, V.; Holinka, L.G.; Gladue, D.P.; Sanford, B.; Krug, P.W.; Lu, X.Q.; Arzt, J.; Reese, B.; Carrillo, C.; Risatti, G.R.; et al. African Swine Fever Virus Georgia Isolate Harboring Deletions of MGF360 and MGF505 Genes Is Attenuated in Swine and Confers Protection against Challenge with Virulent Parental Virus. J. Virol. 2015, 89, 6048–6056. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  16. Alejo, A.; Matamoros, T.; Guerra, M.; Andres, G. A Proteomic Atlas of the African Swine Fever Virus Particle. J. Virol. 2018, 92, 18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  17. Rodriguez, J.M.; Yanez, R.J.; Almazan, F.; Vinuela, E.; Rodriguez, J.F. African swine fever virus encodes a CD2 homolog responsible for the adhesion of erythrocytes to infected cells. J. Virol. 1993, 67, 5312–5320. [Google Scholar] [CrossRef] [Green Version]
  18. Chen, W.; Zhao, D.; He, X.; Liu, R.; Wang, Z.; Zhang, X.; Li, F.; Shan, D.; Chen, H.; Zhang, J.; et al. A seven-gene-deleted African swine fever virus is safe and effective as a live attenuated vaccine in pigs. Sci. China Life Sci. 2020, 63, 623–634. [Google Scholar] [CrossRef]
  19. Bu, Z. Latest progress in prevention and control of African swine fever and vaccine development. Vet. Orientat. 2021, 371, 6–7. [Google Scholar]
  20. Zhang, Y.; Chen, T.; Zhang, J.; Qi, Y.; Miao, F.; Bo, Z.; Wang, L.; Guo, X.; Zhou, X.; Yang, J.; et al. Construction and immunoprotective properties of a gene-deleted vaccine strain of African swine fever virus. Chin. J. Vet. Sci. 2019, 39, 1421–1427. [Google Scholar] [CrossRef]
  21. Borca, M.V.; Ramirez-Medina, E.; Silva, E.; Vuono, E.; Rai, A.; Pruitt, S.; Holinka, L.G.; Velazquez-Salinas, L.; Zhu, J.; Gladue, D.P. Development of a Highly Effective African Swine Fever Virus Vaccine by Deletion of the I177L Gene Results in Sterile Immunity against the Current Epidemic Eurasia Strain. J. Virol. 2020, 94, e02017-19. [Google Scholar] [CrossRef]
  22. Sereda, A.D.; Balyshev, V.M.; Kazakova, A.S.; Imatdinov, A.R.; Kolbasov, D.V. Protective Properties of Attenuated Strains of African Swine Fever Virus Belonging to Seroimmunotypes I–VIII. Pathogens 2020, 9, 274. [Google Scholar] [CrossRef] [Green Version]
  23. Wang, T.; Luo, R.; Sun, Y.; Qiu, H.J. Current efforts towards safe and effective live attenuated vaccines against African swine fever: Challenges and prospects. Infect. Dis. Poverty 2021, 10, 137. [Google Scholar] [CrossRef]
  24. Liu, Y.; Li, Y.; Xie, Z.; Ao, Q.; Di, D.; Yu, W.; Lv, L.; Zhong, Q.; Song, Y.; Liao, X.; et al. Development and in vivo evaluation of MGF100-1R deletion mutant in an African swine fever virus Chinese strain. Vet. Microbiol. 2021, 261, 109208. [Google Scholar] [CrossRef]
  25. Li, D.; Liu, Y.; Qi, X.; Wen, Y.; Li, P.; Ma, Z.; Liu, Y.; Zheng, H.; Liu, Z. African Swine Fever Virus MGF-110-9L-deficient Mutant Has Attenuated Virulence in Pigs. Virol. Sin. 2021, 36, 187–195. [Google Scholar] [CrossRef]
  26. Huang, H.; Dang, W.; Shi, Z.; Ding, M.; Xu, F.; Li, T.; Feng, T.; Zheng, H.; Xiao, S. Identification of African swine fever virus MGF505-2R as a potent inhibitor of innate immunity in vitro. Virol. Sin. 2022, 38, 84–95. [Google Scholar] [CrossRef]
  27. Li, D.; Yang, W.; Li, L.; Li, P.; Ma, Z.; Zhang, J.; Qi, X.; Ren, J.; Ru, Y.; Niu, Q.; et al. African Swine Fever Virus MGF-505-7R Negatively Regulates cGAS-STING-Mediated Signaling Pathway. J. Immunol. 2021, 206, 1844–1857. [Google Scholar] [CrossRef]
  28. Li, D.; Zhang, J.; Yang, W.; Li, P.; Ru, Y.; Kang, W.; Li, L.; Ran, Y.; Zheng, H. African swine fever virus protein MGF-505-7R promotes virulence and pathogenesis by inhibiting JAK1- and JAK2-mediated signaling. J. Biol. Chem. 2021, 297, 101190. [Google Scholar] [CrossRef]
  29. Liu, X.; Ao, D.; Jiang, S.; Xia, N.; Xu, Y.; Shao, Q.; Luo, J.; Wang, H.; Zheng, W.; Chen, N.; et al. African Swine Fever Virus A528R Inhibits TLR8 Mediated NF-κB Activity by Targeting p65 Activation and Nuclear Translocation. Viruses 2021, 13, 2046. [Google Scholar] [CrossRef]
  30. Li, D.; Wu, P.; Liu, H.; Feng, T.; Yang, W.; Ru, Y.; Li, P.; Qi, X.; Shi, Z.; Zheng, H. A QP509L/QP383R-deleted African swine fever virus is highly attenuated in swine but does not confer protection against parental virus challenge. J. Virol. 2021, 96, Jvi0150021. [Google Scholar] [CrossRef]
  31. Liu, H.; Zhu, Z.; Feng, T.; Ma, Z.; Xue, Q.; Wu, P.; Li, P.; Li, S.; Yang, F.; Cao, W.; et al. African Swine Fever Virus E120R Protein Inhibits Interferon Beta Production by Interacting with IRF3 To Block Its Activation. J. Virol. 2021, 95, e0082421. [Google Scholar] [CrossRef]
  32. Yang, J.; Li, S.; Feng, T.; Zhang, X.; Yang, F.; Cao, W.; Chen, H.; Liu, H.; Zhang, K.; Zhu, Z.; et al. African Swine Fever Virus F317L Protein Inhibits NF-κB Activation to Evade Host Immune Response and Promote Viral Replication. mSphere 2021, 6, e00658-21. [Google Scholar] [CrossRef]
  33. Zhang, J. Functional Identification of African Swine Fever Virus L7L-L11L Gene and Vaccine Candidate Strains. Ph.D. Thesis, Ningxia University, Yinchuan, China, 2021. [Google Scholar]
  34. Zhang, K.; Yang, B.; Shen, C.; Zhang, T.; Hao, Y.; Zhang, D.; Liu, H.; Shi, X.; Li, G.; Yang, J.; et al. MGF360-9L Is a Major Virulence Factor Associated with the African Swine Fever Virus by Antagonizing the JAK/STAT Signaling Pathway. mBio 2022, 13, e02330-21. [Google Scholar] [CrossRef]
  35. Zhang, Y.; Ke, J.; Zhang, J.; Yang, J.; Yue, H.; Zhou, X.; Qi, Y.; Zhu, R.; Miao, F.; Li, Q.; et al. African Swine Fever Virus Bearing an I226R Gene Deletion Elicits Robust Immunity in Pigs to African Swine Fever. J. Virol. 2021, 95, e0119921. [Google Scholar] [CrossRef]
  36. Huang, L.; Xu, W.; Liu, H.; Xue, M.; Liu, X.; Zhang, K.; Hu, L.; Li, J.; Liu, X.; Xiang, Z.; et al. African Swine Fever Virus pI215L Negatively Regulates cGAS-STING Signaling Pathway through Recruiting RNF138 to Inhibit K63-Linked Ubiquitination of TBK1. J. Immunol. 2021, 207, 2754–2769. [Google Scholar] [CrossRef]
  37. Li, L.; Fu, J.; Li, J.; Guo, S.; Chen, Q.; Zhang, Y.; Liu, Z.; Tan, C.; Chen, H.; Wang, X. African Swine Fever Virus pI215L Inhibits Type I Interferon Signaling by Targeting Interferon Regulatory Factor 9 for Autophagic Degradation. J. Virol. 2022, 96, e0094422. [Google Scholar] [CrossRef]
  38. Ran, Y.; Li, D.; Xiong, M.G.; Liu, H.N.; Feng, T.; Shi, Z.W.; Li, Y.H.; Wu, H.N.; Wang, S.Y.; Zheng, H.X.; et al. African swine fever virus I267L acts as an important virulence factor by inhibiting RNA polymerase III-RIG-I-mediated innate immunity. PLoS Pathog. 2022, 18, e1010270. [Google Scholar] [CrossRef]
  39. Sun, M.; Yu, S.; Ge, H.; Wang, T.; Li, Y.; Zhou, P.; Pan, L.; Han, Y.; Yang, Y.; Sun, Y.; et al. The A137R Protein of African Swine Fever Virus Inhibits Type I Interferon Production via the Autophagy-Mediated Lysosomal Degradation of TBK1. J. Virol. 2022, 96, e0195721. [Google Scholar] [CrossRef]
  40. Ding, M.; Dang, W.; Liu, H.; Xu, F.; Huang, H.; Sunkang, Y.; Li, T.; Pei, J.; Liu, X.; Zhang, Y.; et al. Combinational Deletions of MGF360-9L and MGF505-7R Attenuated Highly Virulent African Swine Fever Virus and Conferred Protection against Homologous Challenge. J. Virol. 2022, 96, e0032922. [Google Scholar] [CrossRef]
  41. Liu, Y.; Xie, Z.; Li, Y.; Song, Y.; Di, D.; Liu, J.; Gong, L.; Chen, Z.; Wu, J.; Ye, Z.; et al. Evaluation of An I177L gene-based five-gene-deleted African swine fever virus as a live attenuated vaccine in pigs. Emerg. Microbes Infect. 2022, 12, 2148560. [Google Scholar] [CrossRef]
  42. Teklue, T.; Wang, T.; Luo, Y.; Hu, R.; Sun, Y.; Qiu, H.-J. Generation and Evaluation of an African Swine Fever Virus Mutant with Deletion of the CD2v and UK Genes. Vaccines 2020, 8, 763. [Google Scholar] [CrossRef]
  43. Xie, Z.; Liu, Y.; Di, D.; Liu, J.; Gong, L.; Chen, Z.; Li, Y.; Yu, W.; Lv, L.; Zhong, Q.; et al. Protection Evaluation of a Five-Gene-Deleted African Swine Fever Virus Vaccine Candidate Against Homologous Challenge. Front. Microbiol. 2022, 13, 902932. [Google Scholar] [CrossRef]
  44. Gao, Z.; Shao, J.; Chang, Y.; Zhang, G.; Kong, J.; Ge, S.; Chang, H. Predictive analysis of p72 protein antigenic epitopes of African swine fever virus and construction of multi-epitope vaccine. Chin. J. Vet. Med. 2020, 56, 13–17+142–144. [Google Scholar]
  45. Zhou, X.; Mao, R.; Zhu, Z.; Sun, D.; Zhu, Y.; Wang, L.; Qi, M.; Zheng, H. Screening and antigenicity analysis of T-cell epitopes of African swine fever virus CP312R protein. Chin. Vet. Sci. 2022, 52, 410–416. [Google Scholar] [CrossRef]
  46. Cai, J.; Cao, X.; Yang, Y.; Dai, B.; Cao, Q. Analysis of the dominant B and T cell antigenic epitopes of the MGF multigene family of African swine fever virus Pig/HLJ/2018 isolate. Mod. Anim. Husb. Sci. Technol. 2021, 8, 1–5. [Google Scholar] [CrossRef]
  47. Cao, Q.; Dai, B.; Cao, X.; Yang, Y. Bioinformatics analysis of protein pp220 encoded by African swine fever virus Pig/HLJ/2018 strain CP2475L. Swine Ind. Sci. 2021, 38, 100–105. [Google Scholar]
  48. Jia, R.; Zhang, G.; Bai, Y.; Liu, H.; Chen, Y.; Ding, P.; Zhou, J.; Feng, H.; Li, M.; Tian, Y.; et al. Identification of Linear B Cell Epitopes on CD2V Protein of African Swine Fever Virus by Monoclonal Antibodies. Microbiol. Spectr. 2022, 10, e0105221. [Google Scholar] [CrossRef]
  49. Zhang, G.; Liu, W.; Gao, Z.; Chang, Y.; Yang, S.; Peng, Q.; Ge, S.; Kang, B.; Shao, J.; Chang, H. Antigenic and immunogenic properties of recombinant proteins consisting of two immunodominant African swine fever virus proteins fused with bacterial lipoprotein OprI. Virol. J. 2022, 19, 16. [Google Scholar] [CrossRef]
  50. Zhang, G.L.; Liu, W.; Gao, Z.; Yang, S.C.; Zhou, G.Q.; Chang, Y.Y.; Ma, Y.Y.; Liang, X.X.; Shao, J.J.; Chang, H.Y. Antigenicity and immunogenicity of recombinant proteins comprising African swine fever virus proteins p30 and p54 fused to a cell-penetrating peptide. Int. Immunopharmacol. 2021, 101, 108251. [Google Scholar] [CrossRef]
  51. Zhou, X.; Lu, H.; Wu, Z.; Zhang, X.; Zhang, Q.; Zhu, S.; Zhu, H.; Sun, H. Comparison of mucosal immune responses to African swine fever virus antigens intranasally delivered with two different viral vectors. Res. Vet. Sci. 2022, 150, 204–212. [Google Scholar] [CrossRef]
  52. Fang, N.; Yang, B.; Xu, T.; Li, Y.; Li, H.; Zheng, H.; Zhang, A.; Chen, R. Expression and Immunogenicity of Recombinant African Swine Fever Virus Proteins Using the Semliki Forest Virus. Front. Vet. Sci. 2022, 9, 870009. [Google Scholar] [CrossRef] [PubMed]
  53. Chen, L.; Zhang, X.; Shao, G.; Shao, Y.; Hu, Z.; Feng, K.; Xie, Z.; Li, H.; Chen, W.; Lin, W.; et al. Construction and Evaluation of Recombinant Pseudorabies Virus Expressing African Swine Fever Virus Antigen Genes. Front. Vet. Sci. 2022, 9, 832255. [Google Scholar] [CrossRef]
  54. Lu, H.; Zhou, X.; Wu, Z.; Zhang, X.; Zhu, L.; Guo, X.; Zhang, Q.; Zhu, S.; Zhu, H.; Sun, H. Comparison of the mucosal adjuvanticities of two Toll-like receptor ligands for recombinant adenovirus-delivered African swine fever virus fusion antigens. Vet. Immunol. Immunopathol. 2021, 239, 110307. [Google Scholar] [CrossRef] [PubMed]
  55. Chen, C.; Hua, D.; Shi, J.; Tan, Z.; Zhu, M.; Tan, K.; Zhang, L.; Huang, J. Porcine Immunoglobulin Fc Fused P30/P54 Protein of African Swine Fever Virus Displaying on Surface of S. cerevisiae Elicit Strong Antibody Production in Swine. Virol. Sin. 2021, 36, 207–219. [Google Scholar] [CrossRef] [PubMed]
  56. Huang, M. Construction of Recombinant Adenoviral Vector Expressing ASFV Protective Antigen and Immunogenicity Study. Master’s Thesis, Yangzhou University, Yangzhou, China, 2021. [Google Scholar]
  57. Wu, B. Construction of African Swine Fever Virus Vector Vaccine Candidates Based on rAAV and Preliminary Evaluation. Master’s Thesis, Huazhong Agricultural University, Wuhan, China, 2020. [Google Scholar]
  58. Liang, W. Preliminary Study of a Recombinant Pseudorabies Vaccine Expressing the CD2v and P12 Proteins of African Swine Fever Virus. Master’s Thesis, Fujian Normal University, Fuzhou, China, 2021. [Google Scholar]
Figure 1. Publication of ASF vaccine articles in China.
Figure 1. Publication of ASF vaccine articles in China.
Vaccines 11 00762 g001
Figure 2. Created using BioRender.com.
Figure 2. Created using BioRender.com.
Vaccines 11 00762 g002
Table 1. Advances in ASFV seven-gene-deleted attenuated vaccine (HLJ/18-7GD strain) development.
Table 1. Advances in ASFV seven-gene-deleted attenuated vaccine (HLJ/18-7GD strain) development.
PeriodProgress/AchievementsReferences
October–November 2018Isolation and acquisition of endemic ASFV strains in China, completion of whole genome sequence determination and analysis and establishment of infection pathogenesis model[3]
November 2018–May 2019Screening out one safe and effective LAV candidate strain HLJ/18-7GD[18]
December 2019Approval of the gene-deleted LAV candidate strain for environmental release test after national review[19]
June 2019–February 2020Completion of vaccine laboratory product quality research, large-scale production process research and intermediate trial production, as well as biosafety evaluation intermediate test[19]
March 2020Approved for clinical trial of veterinary biological products by the Ministry of Agriculture and Rural Affairs[19]
April–June 2020Biosafety evaluation environmental release testing and Phase I clinical trial conducted in four independent pig farms[19]
August–October 2020Approved by the Ministry of Agriculture and Rural Affairs to enter the biological safety evaluation production test phase, and field biological safety production tests conducted at two enclosed test bases.[19]
September–October 2020Approved by the Ministry of Agriculture and Rural Affairs for conducting Phase II clinical trials at four clinical trial enclosed bases[19]
Table 2. Research progress of ASFV gene-deleted LAV candidate strains in China *.
Table 2. Research progress of ASFV gene-deleted LAV candidate strains in China *.
YearTargeted GenesImmunizing
Dose
Survival RateChallenge Timepoint
(dpv)
Challenge DoseSurvival RateReferences
2019MGF 360/505103 TCID50, 104 TCID5010/1028103 TCID505/5[20]
MGF 360/505 + CD2v103 TCID50, 104 TCID5010/1028103 TCID5010/10
2020MGF 360/505 + CD2v103 TCID50, 105 TCID508/821200 PLD508/8[18]
MGF 360/505103 TCID50, 105 TCID508/821200 PLD508/8
9GL + UK103 TCID50, 105 TCID5012/1221200 PLD500/12
CD2v103 TCID50, 105 TCID503/821//
CD2v + UK103 TCID50, 105 TCID504/821//
CD2v + UK104 TCID505/528104 TCID505/5[42]
2021I226R104 TCID50, 107 TCID5010/1021102.5 TCID50/104 TCID5010/10[35]
MGF 505-7R10 HAD506/621//[27,28]
MGF 110-9L10 HAD503/517//[25]
QP509L/QP383R104 HAD506/617102 HAD500/6[30]
2022MGF360-9L1HAD504/517//[34]
I26710 HAD501/621//[38]
MGF360-9L + MGF505-7R104 HAD506/623102 HAD505/6[40]
EP153R/EP402R + MGF 360-12L/13L/14L105 TCID505/528102 HAD505/5[43]
* Gene-deleted strains with reduced virulence after deletion; single-dose immunization and intramuscular route are primarily used.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Han, N.; Qu, H.; Xu, T.; Hu, Y.; Zhang, Y.; Ge, S. Summary of the Current Status of African Swine Fever Vaccine Development in China. Vaccines 2023, 11, 762. https://doi.org/10.3390/vaccines11040762

AMA Style

Han N, Qu H, Xu T, Hu Y, Zhang Y, Ge S. Summary of the Current Status of African Swine Fever Vaccine Development in China. Vaccines. 2023; 11(4):762. https://doi.org/10.3390/vaccines11040762

Chicago/Turabian Style

Han, Naijun, Hailong Qu, Tiangang Xu, Yongxin Hu, Yongqiang Zhang, and Shengqiang Ge. 2023. "Summary of the Current Status of African Swine Fever Vaccine Development in China" Vaccines 11, no. 4: 762. https://doi.org/10.3390/vaccines11040762

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop