African swine fever virus (ASFV) has substantially spread worldwide, resulting in significant economic losses in the swine industry. Despite extensive research, no ASF vaccine has surpassed the effectiveness of live attenuated vaccines. For instance, the live attenuated vaccine ASFV-G-ΔI177L/ΔLVR has demonstrated good efficacy and safety, along with prolonged persistence of ASF antibodies after vaccination. Therefore, we aimed to evaluate its potential for protection against highly virulent homologous ASF viruses based on changes in the farm environment. To this end, we challenged domestic pigs with a virulent field strain of ASFV following intramuscular immunization with ASFV-G-ΔI177L/ΔLVR. We further assessed its genomic stability and long-term antibody persistence in immunized domestic pigs. All vaccinated pigs exhibited high antibody positivity, with higher levels of antibodies observed at the time of challenge. These high ASF vaccine antibodies were maintained for approximately 2 months after vaccination. In addition, no organ or tissue damage was observed in the vaccinated animals. Our findings demonstrate the applicability of this vaccine candidate in the prevention of ASFV infection in the swine industry.

Background/Objectives: African swine fever (ASF) is a highly lethal disease of domestic pigs and wild suids that continues to cause substantial economic losses worldwide. Despite recent progress in live attenuated ASF vaccine development, evidence supporting durable protection under repeated exposure conditions representative of endemic settings remains limited. Here, we assessed the long-term safety and protective efficacy of a live attenuated ASFV-G-ΔI177L/ΔLVR vaccine using a repeated-challenge experimental design intended to model re-exposure in ASF-endemic regions. Methods: Vaccinated pigs were subjected to homologous virulent ASF virus challenges at multiple intervals, including repeated challenges (three sequential inoculations) and single challenges administered at 8 and 12 weeks post-vaccination. Results: Across all challenge regimens, vaccinated animals survived and remained clinically healthy, including those receiving three challenges, supporting sustained protection under repeated exposure pressure. Animals challenged at 8 or 12 weeks post-vaccination likewise exhibited complete survival, indicating maintained efficacy through at least 12 weeks. No vaccine-associated adverse clinical outcomes were detected over the study period, and post-challenge viral shedding was minimal. Conclusions: Overall, these data demonstrate that the candidate live attenuated ASF vaccine provides excellent protective efficacy and confers sustained protection against homologous ASF virus infection. This result is expected to be equally applicable under repeated exposure conditions in regions with unstable ASF biosecurity, making it a sufficiently promising model experiment for field application in ASF epidemic areas. However, this is still a vaccine variant, and further studies are planned to evaluate its genomic stability and transmissibility.

Recombinant genotype I–II African swine fever virus (ASFV) strains with high virulence have been increasingly reported in China and Vietnam since 2023, raising significant concerns for disease control. In this study, we characterized the hematological, virological, pathological, and immunological dynamics in ASFV-inoculated pigs, with particular emphasis on temporal changes associated with mortality following the onset of viremia. Specific-pathogen-free pigs were intramuscularly inoculated with 1 × 10³ or 1 × 10⁵ HAD₅₀/mL of ASFV LS100 virus strain and developed acute disease characterized by high fever and severe hemorrhagic manifestations. The incubation period ranged from 3 to 5 days, with mortality occurring between 6 and 10 days post-inoculation (dpi). Viral genomic DNA was detected in blood, oral swabs, and rectal swabs as early as 2–4 dpi. Pathological examination revealed prominent necrotic skin lesions and joint swelling. Although hematological parameters and serum biochemical profiles were comparable between high- and low-dose groups, differences in viral load distribution were observed. Notably, cytokine profiling in whole blood revealed a strong and persistent upregulation of pro-inflammatory mediators, including IL-1β, IL-6, IL-12p40, TNF-α, IFN-γ, CCL2, CCL3, CCL14, CXCL9, and CXCL10, which correlated with persistent fever from 2 to 7 dpi. Collectively, these findings confirm that naturally occurring recombinant genotype I–II ASFV strains are highly virulent and capable of inducing severe systemic inflammation. Their continued circulation poses substantial challenges for ASF control and prevention in Vietnam and threatens the global swine industry.

Background/Objectives: African swine fever (ASF) is a highly lethal disease of domestic pigs and wild suids that continues to cause substantial economic losses worldwide. Despite recent progress in live-attenuated ASF vaccine development, evidence supporting durable protection under repeated exposure conditions representative of endemic settings remains limited. Here, we assessed the long-term safety and protective efficacy of a live-attenuated ASFV-G-ΔI177L/ΔLVR vaccine using a repeated-challenge experimental design intended to model re-exposure in ASF-endemic regions. Methods: Vaccinated pigs were subjected to homologous virulent ASF virus challenges at multiple intervals, including repeated challenges (three sequential inoculations) and single challenges administered at 8 and 12 weeks post-vaccination. Results: Across all challenge regimens, vaccinated animals survived and remained clinically healthy, including those receiving three challenges, supporting sustained protection under repeated exposure pressure. Animals challenged at 8 or 12 weeks post-vaccination likewise exhibited complete survival, indicating maintained efficacy through at least 12 weeks. No vaccine-associated adverse clinical outcomes were detected over the study period, and post-challenge viral shedding was minimal. Conclusions: Overall, these data demonstrate that the candidate live-attenuated ASF vaccine provides excellent protective efficacy and confers sustained protection against homologous ASF virus infection. This result is expected to be equally applicable under repeated exposure conditions in regions with unstable ASF biosecurity, making it a sufficiently promising model experiment for field application in ASF epidemic areas.

Background/Objective: African swine fever (ASF), caused by African swine fever virus (ASFV), is a highly contagious viral disease affecting domestic pigs and wild boars, causing severe economic losses. Although commercial ASF vaccines have recently been approved in Vietnam, controlling ASF transmission remains challenging. Since injection-based vaccination is impractical for wild boars, oral vaccination is considered essential. This study aimed to evaluate the safety, immunogenicity, protective efficacy, and dose-related outcomes of ASFV-G-ΔI177L/ΔLVR, a live attenuated ASFV vaccine candidate with deletion in the I177L gene and left variable region (LVR), administered orally to convention pigs. Methods: The ASFV-G-ΔI177L/ΔLVR vaccine candidate was orally administered to conventional pigs at three dose levels (10^2.25, 10^5.0, and 10^6.0 TCID₅₀/dose). At 28 days post-vaccination, pigs were challenged intramuscularly with a virulent ASFV field strain at 10^2.0 HAD₅₀/mL and monitored clinically. Protection was assessed by ASFV-specific antibody responses (p32) and survival following challenge. Results: Oral immunization was well tolerated, with no vaccine-associated clinical signs observed before challenge. Following challenge, vaccinated pigs showed different protective outcomes among the tested dose groups, with survival rates of 1/4 (10^2.25 TCID₅₀/dose), 4/4 (10^5.0 TCID₅₀/dose), and 3/4 (10^6.0 TCID₅₀/dose), respectively. Pigs that succumbed to infection showed neither detectable viremia nor ASFV-specific antibodies before challenge, suggesting incomplete vaccine uptake may have resulted in insufficient immune induction rather than an adverse effect associated with vaccination. In contrast, pigs that seroconverted prior to challenge were fully protected and exhibited lower viral loads than the control animals. Conclusions: ASFV-G-ΔI177L/ΔLVR was well tolerated as an oral live attenuated vaccine candidate and induced protective immunity against virulent ASFV challenge under the present experimental conditions. Notably, complete protection was observed in the 10^5.0 TCID₅₀/dose group, supporting the potential of this vaccine candidate for oral immunization strategies against ASF. However, the present data do not allow a definitive conclusion regarding the dose–response relationship, and further studies with larger group sizes and field-relevant models are needed to refine dose selection and practical applicability, particularly for wild boar vaccination.