African swine fever (ASF) remains one of the most pressing threats to global animal health and food security. With outbreaks continuing across Europe, Asia, and parts of the Americas, recent research has provided critical insights into the biology, transmission, and immune evasion tactics of the African swine fever virus (ASFV). This round-up highlights seven important studies published in 2025 that advance our understanding of ASFV pathogenesis, diagnostics, and vaccine challenges—offering direction for scientists, policymakers, and biosecurity practitioners worldwide.
Antibodies That Worsen the Disease: A Warning for Vaccine Developers
A recent study in the Journal of Virology found that some antibodies raised against ASFV may actually worsen disease outcomes. In pigs immunized with a specific viral protein called pA137R, clinical symptoms were more severe and appeared earlier than in unvaccinated pigs after virus exposure. The researchers attributed this to a process known as antibody-dependent enhancement (ADE), where antibodies—rather than protecting the host—aid the virus in infecting immune cells.
This is a particularly troubling discovery for vaccine development. The study showed that ADE was facilitated by Fc gamma receptors on immune cells, which helped the virus gain entry and replicate more efficiently. The findings serve as a crucial reminder that not all immune responses are protective, and that careful antigen selection is essential to avoid inadvertently exacerbating the disease in vaccinated animals.
ASFV Does Not Invade the Nucleus After All
Decades-old assumptions about ASFV’s replication strategy were upended by researchers using cutting-edge molecular imaging. Contrary to earlier claims that ASFV might briefly enter the cell nucleus to replicate its DNA, the new data published in the Journal of Virology show that all steps of the virus’s replication and transcription occur entirely within the cytoplasm.
This is an important clarification, not just for basic virology, but for drug development. Cytoplasmic replication means the virus can be targeted with therapeutics that don’t need to cross the nuclear membrane, making drug design more straightforward. Understanding this step also helps explain how ASFV avoids some of the host’s nuclear defenses, and supports efforts to model infection dynamics more accurately.
ASFV Hijacks Immune Cells to Spread via Apoptotic Bodies
In a counterintuitive finding, scientists discovered that ASFV enhances rather than suppresses the ability of immune cells called alveolar macrophages to engulf bacteria and dying cells. This increased phagocytic activity is mediated through the upregulation of a receptor called CD14 and is used by the virus to spread between cells.
The virus essentially uses immune system mechanisms against the host. By boosting the phagocytosis of apoptotic bodies—fragments of infected dying cells—ASFV ensures that nearby macrophages ingest virus-laden debris, facilitating its own transmission. At the same time, this process can amplify inflammation, worsening disease and complicating co-infections with bacteria. This finding, published in the Journal of Virology, adds a new layer to our understanding of ASFV’s manipulation of host immunity.
ASFV Protein p22 Helps the Virus Evade the Immune System
Research published this month in PLOS Pathogens identifies a novel function for the ASFV protein p22: it suppresses a key antiviral signaling pathway in host cells. The JAK-STAT pathway is responsible for relaying signals from interferons—potent antiviral cytokines—that help coordinate the immune response to viral infection. The p22 protein interferes with this process by promoting the autophagic degradation of the type I interferon receptor (IFNAR1).
This tactic allows ASFV to effectively “deafen” infected cells to warning signals from the immune system, giving the virus more time and freedom to replicate. The degradation is facilitated through interaction with a host protein called TAX1BP1. This discovery not only explains part of ASFV’s stealth capabilities, but also opens new avenues for antiviral intervention by preserving or mimicking interferon signaling during early infection.
Rapid Whole-Genome Sequencing on a Portable Device
Speed and accuracy are everything when an outbreak strikes. A U.S.-based research team has published a pre-print paper showing a method to rapidly sequence the entire genome of ASFV and Classical Swine Fever Virus (CSFV) using the compact, portable MinION sequencing device. By designing targeted primer sets, they were able to achieve over 99% genome coverage for ASFV with more than 1000X depth of coverage—sufficient for mutation tracking, genotype confirmation, and outbreak tracing.
This method is particularly useful for field applications and could become a cornerstone of emergency response in disease outbreaks. Rapid sequencing enables real-time insights into viral evolution, helps trace the source of infections, and supports more informed decision-making around trade, vaccination, and quarantine policies.
Synthetic Biology Breakthrough: Building ASFV from Scratch for Vaccine Design
A major technical barrier in ASFV research has long been the virus’s large and complex genome, which makes it difficult to manipulate and study using traditional molecular tools. In a 2025 breakthrough published in Science Advances, researchers developed the first synthetic genomics platform for ASFV, allowing scientists to engineer the virus in the lab from cloned DNA.
This new system, built in Saccharomyces cerevisiae (baker’s yeast), enables the assembly and modification of the full ASFV genome—opening the door to reverse genetics approaches that were previously impossible. Using this platform, the team successfully generated infectious ASFV particles and demonstrated that engineered deletions or modifications in key genes could attenuate the virus or affect its ability to replicate.
This capability is transformative. It means scientists can now test specific hypotheses about ASFV gene function, build rationally attenuated vaccine strains, and rapidly adapt vaccines to new viral variants. Importantly, the system was tested under high-biocontainment conditions to ensure safety and biosurety.
A Promising Subunit Vaccine: Sterile Immunity Achieved with ASFV CD2v Protein
A longstanding hurdle in controlling ASF has been the lack of a safe, effective, and scalable vaccine that protects pigs without causing disease. In a major step forward, a team of researchers developed a subunit vaccine based on the ASFV CD2v protein that successfully conferred sterile immunity—complete protection with no detectable viral replication—against lethal ASFV challenge in pigs.
The CD2v protein, known to play a key role in ASFV’s ability to bind to host cells and modulate immune responses, was used as the sole antigen in the vaccine. It was formulated with a proprietary adjuvant to enhance the immune response. Pigs vaccinated with this formulation showed no signs of disease, no virus in tissues or blood, and no virus transmission to contact animals after challenge with a virulent ASFV strain.
This result is particularly important because most previous ASF vaccine efforts relied on live-attenuated viruses, which carry safety risks including the potential for reversion to virulence. A subunit vaccine, in contrast, does not involve any live virus, making it safer for production, distribution, and use in outbreak settings.
If these results are replicated in large-scale trials and across different ASFV genotypes, this approach could be a game changer—offering a viable path to mass immunization and global ASF control. It also illustrates the power of structure-guided antigen design and adjuvant optimization in developing next-generation veterinary vaccines.
Summary: Progress and Challenges in the ASFV Research Landscape
The research published in 2025 marks a turning point in the fight against African swine fever. From uncovering how antibodies may worsen disease to identifying viral mechanisms that hijack immune pathways, this year’s studies have deepened our understanding of ASFV pathogenesis and host interactions. The field is also advancing rapidly in applied areas, with two major breakthroughs: the development of a synthetic genomics platform for precise viral engineering, and the first demonstration of sterile immunity in pigs using a CD2v-based subunit vaccine.
These advances are not only scientifically impressive—they are strategically important. The synthetic platform enables rational vaccine design and accelerated functional studies, while the CD2v vaccine offers a safer, scalable alternative to live-attenuated formulations. Portable whole-genome sequencing tools are improving outbreak response capacity, and clearer models of immune evasion are refining our targets for antiviral drugs and diagnostics.
Yet challenges remain. The risk of antibody-dependent enhancement, the complexity of ASFV’s immune modulation strategies, and the need for vaccines effective across diverse genotypes all highlight how formidable this virus continues to be. ASFV still poses a grave risk to global food security, rural livelihoods, and national economies.
Continued investment in ASF research—paired with strong international coordination, field validation, and technology transfer—will be critical to converting these scientific breakthroughs into sustainable disease control programs. The progress is real, but the work is far from over.
Sources and Further Reading
- Anti-pA137R antibodies exacerbate ASFV pathogenicity in pigs. Journal of Virology, 29 May 2025.
- Revisiting the early event of ASFV DNA replication. Journal of Virology, 30 May 2025.
- ASFV infection enhances CD14-dependent phagocytosis in porcine macrophages. Journal of Virology, 12 June 2025.
- ASFV p22 protein suppresses immune signaling via IFNAR1 degradation. PLOS Pathogens, 16 July 2025.
- Targeted whole-genome sequencing of ASFV and CSFV. bioRxiv pre-print, 18 July 2052.
- A synthetic genomics-based African swine fever virus engineering platform. Science Advances, 26 March 2025.
- Advances in African swine fever virus molecular biology and host interactions contributing to new tools for control. Journal of Virology, 9 May 2025.