Advances in African swine fever vaccine development: challenges and prospects.

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Learn more: PMC Disclaimer | PMC Copyright Notice J Vet Sci . 2026 Jan 30;27(3):e16. doi: 10.4142/jvs.25160 Advances in African swine fever vaccine development: challenges and prospects Doddy Irawan Setyo Utomo 1, ✉ , NLP Indi Dharmayanti 2 , Masteria Yunovilsa Putra 1, 3, ✉ Author information Article notes Copyright and License information 1 Research Center for Vaccine and Drug, Research Organization for Health, National Research and Innovation Agency (BRIN), Bogor 16911, Indonesia. 2 Research Organization for Health, National Research and Innovation Agency (BRIN), Bogor 16911, Indonesia. 3 Faculty of Pharmacy, Universitas Indonesia, Depok, West Java 16424, Indonesia. ✉ Corresponding author: Doddy Irawan Setyo Utomo. Research Center for Vaccine and Drug, Research Organization for Health, National Research and Innovation Agency (BRIN), The Meatpro Building, Kawasan Sains dan Teknologi (KST) Soekarno, Jalan Raya Jakarta-Bogor KM 46, Cibinong, Bogor 16911, Indonesia. dodd002@brin.go.id ✉ Corresponding author: Masteria Yunovilsa Putra. Research Center for Vaccine and Drug, Research Organization for Health, National Research and Innovation Agency (BRIN), The Meatpro Building, Kawasan Sains dan Teknologi (KST) Soekarno, Jalan Raya Jakarta-Bogor KM 46, Cibinong, Bogor 16911, Indonesia. Faculty of Pharmacy, Universitas Indonesia, Jalan Prof. DR. Mahar Mardjono, Pondok Cina, Beji, Depok, West Java 16424, Indonesia. mast001@brin.go.id ✉ Corresponding author. Received 2025 Jun 12; Revised 2025 Sep 10; Accepted 2025 Nov 9; Collection date 2026 May. © 2026 The Korean Society of Veterinary Science This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0 ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. PMC Copyright notice PMCID: PMC13236470  PMID: 42225599 Abstract Importance African swine fever (ASF) is a devastating transboundary disease of domestic pigs and wild boar, causing severe economic losses with mortality approaching 100% in acute infections. Despite decades of research, there is no widely available, internationally licensed ASF vaccine, and control remains dependent on biosecurity, culling, and movement restrictions. The complex biology of African swine fever virus (ASFV), immune evasion, and incomplete understanding of protective immunity continue to impede vaccine development. Observations Vaccine development includes live attenuated vaccines (LAVs), subunit vaccines, DNA vaccines, viral vectors, and newer approaches such as virus-like particles (VLPs) and mRNA platforms. LAVs remain the most promising in controlled studies (e.g., BA71ΔCD2) and include candidates with limited emergency authorizations in some settings (e.g., HLJ/18-7GD), but safety concerns (reversion risk), environmental persistence, and DIVA limitations remain major barriers. Subunit and nucleic acid vaccines offer improved safety but have shown limited protection in challenge studies. Advances in structural biology, genomics, and immunology are accelerating rational design, with VLPs emerging as a promising next-generation approach to balance safety and immunogenicity. Conclusions and Relevance Recent progress in ASFV structural understanding, immune correlates of protection, and vaccine engineering supports cautious optimism. Success will likely require standardized evaluation, robust DIVA strategies, and coordinated international development and deployment pathways. Keywords: DIVA, live attenuated vaccines, virus-like particles, viral vectors, mRNA vaccines INTRODUCTION African swine fever (ASF) is a highly contagious viral disease of domestic pigs and wild boar caused by the ASF virus (ASFV), with case fatality rates approaching 100% in acute infections [ 1 , 2 ]. Since its first description in Kenya in 1921, ASF has evolved from a geographically limited endemic disease to a global threat, with devastating outbreaks reported across Europe, Asia, and the Americas [ 3 , 4 ]. The current pandemic, particularly the catastrophic spread through China since 2018, has highlighted the urgent need for effective control measures [ 5 , 6 ]. The ASFV is a large, complex double-stranded DNA virus and the sole member of the family Asfarviridae [ 7 ]. The virus possesses a sophisticated multilayered structure consisting of an icosahedral nucleocapsid surrounded by an inner lipid envelope, an outer protein shell, and an external envelope derived from the host cell membranes [ 8 ]. The viral genome ranges from 170–194 kb in length and encodes more than 150 proteins, many involved in immune evasion or having unknown functions [ 8 , 9 ]. The major capsid protein p72, encoded by the B646L gene, forms the primary structural component of the icosahedral capsid and serves as the basis for viral genotype classification [ 10 ]. Other important structural proteins include p54 (attachment protein), p30 (structural protein involved in virus entry), and CD2v (hemadsorption protein associated with virulence) [ 11 , 12 ]. The ASFV primarily infects cells of the mononuclear phagocyte system and has developed sophisticated strategies to evade the innate and adaptive immune responses [ 10 , 11 ]. The virus exists in 24 recognized genotypes based on the p72 capsid protein sequence, presenting challenges for cross-protective immunity [ 12 , 13 ]. Current ASF control relies exclusively on strict biosecurity measures, surveillance, movement restrictions, and the culling of infected herds [ 14 ]. These approaches, while effective in some contexts, are economically devastating and may be impractical in regions with a high pig density, limited veterinary infrastructure, or extensive wild boar populations [ 15 , 16 ]. The absence of therapeutic interventions or vaccines leaves the global swine industry vulnerable to the continued spread of ASF and associated economic losses estimated in billions of dollars annually [ 17 ]. The complexity of ASFV biology presents unique challenges for vaccine development. Unlike most viral pathogens, a natural ASFV infection does not induce sterilizing immunity, and the antibody responses are typically non-neutralizing [ 18 , 19 ]. Evidence suggests that the cellular immunity, particularly CD8+ T cell responses, may be crucial for protection, even though the precise correlates of immunity remain poorly defined [ 20 , 21 ]. These characteristics have contributed to the failure of conventional vaccine approaches and necessitated innovative strategies for ASF vaccine development. This review reports a comprehensive analysis of current ASF vaccine development efforts, examining the scientific challenges, promising candidates, and emerging technologies that may facilitate breakthrough developments in this critical field. METHODS This narrative review was prepared using a structured literature search of peer-reviewed publications (1960–2024) indexed in PubMed, Scopus, and Web of Science. Search terms included combinations of ‘African swine fever,’ ‘ASFV,’ ‘vaccine,’ ‘live attenuated,’ ‘subunit,’ ‘viral vector,’ ‘DNA,’ ‘mRNA,’ and ‘virus-like particle.’ Articles were selected to provide historical context and to emphasize recent advances (2020–2024). Formal risk-of-bias assessment and meta-analysis were not performed, consistent with the narrative review design. The selection criteria included studies reporting experimental vaccine evaluations in swine, mechanistic investigations of ASFV immune evasion, structural biology research relevant to vaccine design, and regulatory or field implementation studies. Emphasis was placed on recent developments (2020–2024) while incorporating foundational research to provide a historical context. Data synthesis focused on vaccine platform comparisons, efficacy outcomes, safety profiles, and technological advances. Particular attention was given to live attenuated vaccines (LAVs) with deletion mutations, novel platforms such as virus-like particles (VLPs), and promising combination approaches in preclinical or field evaluations. OBSERVATIONS ASFV biology and vaccine development challenges The ASFV presents unique biological characteristics that complicate vaccine development efforts. The virus possesses a complex, multilayered structure with an icosahedral capsid containing primarily the p72 protein, surrounded by lipid envelopes derived from cellular membranes [ 22 , 23 ]. This sophisticated architecture contributes to environmental stability and may influence the antigen presentation pathways crucial for vaccine efficacy. The immune evasion mechanisms used by the ASFV present significant challenges for vaccine development, as detailed in Table 1 , where the “Development status” column represents the current developmental stage of countermeasures designed to overcome each specific immune evasion mechanism. Table 1. African swine fever virus immune evasion mechanisms and vaccine countermeasures by country/region. Immune evasion mechanism Viral protein Vaccine strategy Development status Country/region IFN inhibition MGF 360/505 LAV with MGF deletions Advanced trials China, Vietnam [ 34 , 35 ] TLR inhibition I329L Modified protein subunits Preclinical Spain, UK [ 46 , 47 ] NF-κB suppression A238L Gene deletion LAVs Preclinical USA [ 39 , 40 ] Apoptosis inhibition A179L, A224L Targeted gene deletions Development USA, Spain [ 25 , 32 ] MHC-I downregulation Unknown VLP enhanced presentation Early stage Multiple countries [ 59 , 60 ] Antigenic variation Structural proteins Multi-genotype vaccines Research Global initiatives [ 28 , 29 ] Cytoplasmic replication Viral machinery Cytoplasmic antigen targeting Research EU, USA [ 24 , 67 ] Open in a new tab Entries reflect proposed or hypothesized strategies unless supported by experimental validation. IFN, interferon; MGF, multigene family; LAV, live attenuated vaccine; TLR, toll-like receptor; NF-κB, nuclear factor-κB; MHC, major histocompatibility complex; VLP, virus-like particle. The virus replicates exclusively in the cytoplasm, avoiding the nuclear antiviral responses but complicating nucleic acid vaccine approaches that depend on nuclear processing [ 24 ]. The ASFV has evolved numerous immune evasion mechanisms, including the inhibition of type I interferon responses through multigene family (MGF) 360 and MGF 505 proteins, suppression of apoptosis via Bcl-2 homologs, and downregulation of major histocompatibility complex class I presentation [ 25 , 26 , 27 ] ( Table 1 ). The genetic diversity among ASFV isolates presents additional challenges for vaccine development. Although 24 genotypes are recognized based on p72 sequencing, functional antigenic differences may not correlate directly with the genetic classification [ 28 ]. Most vaccine candidates show efficacy against homologous strains but limited cross-protection against heterologous challenges, highlighting the need for broadly protective approaches [ 29 , 30 ]. LAV development LAVs represent the most advanced approach in ASF vaccine development, offering the potential to stimulate the humoral and cellular immune responses [ 31 ]. Several promising candidates have emerged through targeted gene deletion strategies. The BA71ΔCD2 strain, lacking the CD2v gene involved in hemadsorption and virulence, has shown complete protection against a homologous challenge and partial protection against heterologous strains [ 32 , 33 ]. Safety studies indicate stable attenuation with no reversion to virulence observed in extended passages. Chinese researchers have developed the HLJ/18-7GD strain containing deletions in multiple virulence genes, including MGF 360 and MGF 505 [ 34 ]. Field trials in China and Vietnam have shown promising efficacy and safety profiles, with regulatory approval granted in Vietnam for emergency use [ 35 , 36 ]. The naturally attenuated OURT88/3 isolate continues to be evaluated as a vaccine candidate, particularly in combination with boost strategies [ 37 ]. Recent studies have shown that OURT88/3 immunization followed by a boost with related antigens can provide robust protection against a virulent challenge [ 38 ]. Advanced genetic engineering approaches using CRISPR-Cas9 technology enable a precise deletion of multiple virulence genes while preserving immunogenic proteins [ 39 ]. These next-generation LAVs aim to improve the safety profiles while maintaining protective efficacy ( Table 2 ). Table 2. Leading African swine fever vaccine candidates in development. Candidate Type Key features Development stage References BA71ΔCD2 LAV CD2v gene deletion Preclinical trials [ 32 , 33 ] HLJ/18-7GD LAV Multiple gene deletions Field evaluation; emergency authorization in Vietnam [ 34 , 35 ] OURT88/3 LAV Natural attenuation Preclinical evaluation [ 37 , 38 ] p30/p54/p72 cocktail Subunit Multi-antigen combination Preclinical trials [ 46 , 47 ] MVA-ASFV Viral vector Modified vaccinia vector Preclinical trials [ 48 , 50 ] ASFV-VLP VLP Structural protein particles Early preclinical [ 59 , 60 ] Open in a new tab LAV, live attenuated vaccine; MVA, modified vaccinia Ankara; ASFV, African swine fever virus; VLP, virus-like particle. Despite the promising results, LAV development faces significant regulatory and practical challenges. In addition, safety concerns regarding the potential reversion to virulence, environmental persistence, and spread to wildlife populations remain paramount [ 40 , 41 ]. Most LAV candidates lack validated differentiating infected from vaccinated animals (DIVA) capabilities essential for surveillance and trade facilitation [ 42 ]. Subunit and vector-based approaches Subunit vaccines have improved safety profiles compared to LAVs but have limited efficacy according to challenge studies [ 43 ]. Individual ASFV structural proteins, including p30, p54, p72, and CD2v, have been evaluated as vaccine antigens with minimal success [ 44 , 45 ]. Recent efforts have focused on multi-antigen approaches, recognizing that single proteins may be insufficient for protection [ 46 ]. Combinations of structural proteins expressed in various systems, including baculovirus, mammalian cells, and plant-based platforms, have improved immunogenicity compared to individual antigens, but the protection remains incomplete [ 47 , 48 ] ( Table 3 ). Table 3. African swine fever virus proteins evaluated as vaccine antigens. Protein Gene Function Vaccine platform Immunogenicity Protection level References p72 B646L Major capsid protein Subunit, VLP, LAV High antibody response Limited alone [ 18 , 44 ] p54 E183L Attachment protein Subunit, VLP, vector Moderate Limited [ 44 , 68 ] p30 CP204L Attachment protein Subunit, vector, DNA Moderate Partial [ 44 , 46 ] CD2v EP402R Hemadsorption, virulence Subunit, VLP, LAV Variable Partial [ 32 , 60 ] p17 D117L Structural protein VLP Low Unknown [ 59 ] p22 KP177R Inner membrane Subunit Low Limited [ 46 ] p12 O61R Membrane protein Subunit Low Limited [ 22 ] p14 E120R Nucleocapsid LAV Moderate Partial [ 25 ] Open in a new tab VLP, virus-like particle; LAV, live attenuated vaccine. Viral vector-based vaccines using modified vaccinia Ankara, adenoviruses, and other platforms have been evaluated for ASFV antigen delivery [ 49 , 50 ]. Prime-boost strategies combining different vectors or platforms have shown enhanced immune responses compared to single-vector approaches [ 51 ]. DNA vaccines encoding ASFV antigens have the ability to induce antibody and T cell responses but provide limited protection against a virulent challenge [ 52 , 53 ]. Combination approaches using DNA priming followed by a protein or vector boost have shown improved outcomes in preliminary studies [ 54 ]. VLPs: next-generation platform VLPs are a promising technological advance that combines the safety advantages of subunit vaccines with the immunogenic potential of whole-virus particles [ 55 , 56 ]. VLPs maintain the native structural organization of viral proteins while lacking infectious genetic material. The recent advances in ASFV structural biology through cryo-electron microscopy have facilitated rational VLP design [ 57 , 58 ]. The successful expression of ASFV VLPs containing combinations of structural proteins, including p72, p54, p30, and CD2v, has been achieved using baculovirus expression systems [ 59 ]. In parallel, gene-deleted ASFV variants have been investigated for attenuation and partial protection in challenge models [ 60 ]. Recent work exploring virus-like particle strategies and antigen-display particle vectors has shown induction of both humoral and cellular responses against ASFV antigens in preclinical studies [ 59 , 61 ]. Enhanced VLP designs incorporating immunostimulatory molecules or targeting strategies for specific immune cell populations, such as porcine macrophages, have been investigated to improve immunogenicity and cellular uptake [ 62 , 63 ]. Manufacturing challenges for VLP-based vaccines include scale-up production, quality control, and stability optimization [ 64 ]. On the other hand, established VLP production platforms from other vaccine programs provide a foundation for ASFV VLP development and commercialization. Emerging technologies and novel approaches mRNA vaccine technology, validated through coronavirus disease 2019 vaccine development, is being adapted for ASFV applications [ 65 ]. Early studies have suggested that mRNA vaccines encoding ASFV antigens can induce immune responses, though challenge studies are pending [ 66 ]. Computational approaches, including reverse vaccinology and immunoinformatics, are accelerating antigen identification and epitope mapping [ 67 , 68 ]. These technologies have identified previously overlooked ASFV proteins that may contribute to protective immunity. Combination vaccine strategies integrating multiple platforms show particular-promise [ 69 ]. Heterologous prime-boost approaches using different vaccine technologies may overcome the limitations of individual platforms while maximizing immune stimulation ( Table 4 ). Table 4. Comparison of African swine fever vaccine platforms with supporting references. Platform Principle Efficacy Safety DIVA compatibility Main challenges Key references Inactivated Chemically inactivated virus No protection High No Poor immunogenicity [ 18 , 43 ] Live Attenuated Gene-deleted virus Best protection Low Variable Safety, reversion risk [ 31 , 32 , 34 ] Subunit Recombinant proteins Limited High Yes Low immunogenicity [ 43 , 44 , 46 ] DNA Plasmids encoding antigens Limited High Yes Poor expression [ 52 , 53 , 54 ] Viral vectors Recombinant vectors Moderate Moderate Yes Pre-existing immunity [ 49 , 50 , 51 ] VLP Multiprotein particles Moderate High Yes Production complexity [ 55 , 59 , 61 ] Open in a new tab DIVA, differentiating infected from vaccinated animals; VLP, virus-like particle. Regulatory and implementation challenges Regulatory approval for ASF vaccines faces stringent requirements because of safety concerns and the need for robust efficacy data [ 70 ]. Regulatory agencies require extensive safety, efficacy, and quality data that may take years to generate, particularly for LAV candidates [ 71 ]. Manufacturing scalability poses additional challenges because the ASFV does not propagate efficiently in continuous cell lines, often requiring primary macrophages for virus production [ 72 ]. This complicates large-scale manufacturing for LAV and inactivated vaccine approaches. DIVA capability remains essential for vaccine acceptance, enabling differentiation between vaccinated and infected animals for surveillance and trade purposes [ 73 ]. Integration of DIVA markers into vaccine designs is essential for regulatory approval and field implementation. DISCUSSION Current status and future directions The landscape of ASF vaccine development has evolved significantly in recent years, with multiple promising candidates advancing through preclinical and field evaluations. LAVs are the most advanced approach, showing superior efficacy compared to other platforms, but safety concerns continue to challenge regulatory acceptance [ 74 , 75 ]. The success of HLJ/18-7GD field trials in Asia represents a significant milestone, providing the first large-scale evidence of effective ASF vaccination under field conditions [ 76 ]. Nevertheless, questions remain regarding the long-term safety, cross-protection against diverse ASFV strains, and optimal deployment strategies. Subunit and nucleic acid-based vaccines, while safer than LAVs, require significant advances to achieve protective efficacy [ 77 ]. The integration of novel adjuvants, delivery systems, and multi-antigen formulations may improve their performance. VLP technology offers a promising middle ground, potentially enhancing immunogenicity compared to traditional subunit vaccines while maintaining excellent safety profiles [ 78 ]. Integration of multiple technologies Future ASF vaccine development may benefit from the integration of multiple technologies rather than reliance on single platforms [ 79 ]. Heterologous prime-boost strategies combining LAV, subunit, or vector-based approaches could potentially optimize the safety and efficacy profiles. Combination approaches might also address the challenge of antigenic diversity among ASFV strains [ 80 ]. Vaccines incorporating antigens from multiple genotypes or broadly conserved epitopes might provide enhanced cross-protection against diverse field isolates. The development of next-generation adjuvants and delivery systems optimized specifically for ASFV vaccines represents another critical area for advancement [ 81 ]. Understanding the precise immune correlates required for protection will enable rational adjuvant selection and formulation optimization. Standardization and collaborative efforts Progress in ASF vaccine development would benefit significantly from standard evaluation protocols, challenge models, and immunological assays [ 82 ]. Harmonized approaches would allow comparisons across studies and accelerate the identification of promising candidates. International collaborative initiatives involving academic institutions, industry partners, and regulatory agencies could help address the complex challenges of ASF vaccine development [ 83 ]. Shared resources, coordinated research efforts, and aligned regulatory frameworks would expedite the progress toward effective vaccines. Open data sharing and collaborative research networks are essential for addressing the multifaceted challenges of ASF vaccine development [ 84 ]. The complex biology of the ASFV and the scale of the global ASF threat require coordinated international efforts that transcend traditional competitive boundaries. Implementation considerations Beyond technical development, successful ASF control through vaccination will require the careful consideration of implementation strategies [ 85 ]. The development of effective DIVA capabilities, robust surveillance systems, and coordinated deployment plans addressing domestic and wild pig populations will be essential. Economic analyses and stakeholder engagement will be necessary to ensure that eventual vaccines are cost-effective and widely adopted across diverse production systems [ 86 ]. Different epidemiological contexts, production systems, and resource availability will be crucial considerations for optimal vaccine deployment. The potential for oral vaccination delivery, particularly for wild boar populations, is an important consideration for comprehensive ASF control strategies [ 87 ]. The development of stable, palatable vaccine formulations suitable for wildlife applications could significantly enhance disease control efforts. Technological innovations and future prospects Advances in structural biology, synthetic biology, and computational vaccine design continue to provide new tools for ASF vaccine development [ 88 ]. High-resolution structural studies of ASFV proteins and host–virus interactions offer opportunities for rational vaccine design and optimization. The application of machine learning and artificial intelligence approaches to vaccine development may accelerate antigen identification, epitope prediction, and formulation optimization [ 89 ]. These technologies could significantly reduce the time and cost associated with vaccine development. Emerging platforms such as nanoparticle vaccines, self-amplifying RNA, and targeted delivery systems may offer additional opportunities for ASF vaccine advancement [ 90 ]. The rapid pace of vaccine technology development provides multiple avenues for addressing the unique challenges posed by the ASFV. Food security and economic implications The development of effective ASF vaccines has implications extending far beyond animal health, directly impacting global food security and economic stability [ 91 ]. ASF outbreaks threaten food security by reducing pork availability, a major protein source worldwide, particularly in Asia, where pork consumption is highest. The disease can devastate local and regional food systems, leading to protein shortages and increased food prices that disproportionately affect vulnerable populations [ 92 ]. The interconnected nature of global food supply chains means that ASF outbreaks in major pork-producing regions can have worldwide economic impacts [ 92 ]. Effective vaccination strategies could help stabilize pork production and reduce the economic volatility associated with ASF outbreaks. ASF vaccines could provide critical protection for vulnerable populations in regions where pig production supports rural livelihoods and food security [ 93 ]. Hence, the development of affordable, effective vaccines suitable for diverse production systems remains a global health priority. Footnotes Funding: This research was supported by the Research Program Initiative (Rumah Program) under the Research Organization for Health, National Research and Innovation Agency (BRIN), Republic of Indonesia . Conflict of Interest: The authors declare no conflicts of interest. Data Availability Statement: This article is a narrative review and does not include any original data. Author Contributions: Conceptualization: Utomo DIS. Data curation: Utomo DIS. Formal analysis: Utomo DIS. Funding acquisition: Putra MY. Investigation: Utomo DIS. Methodology: Utomo DIS. 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