Building on recent insights into ASFV biology and host immunity, this article explores how VAX4ASF is translating scientific knowledge into innovative vaccine designs that balance strong protection with enhanced safety.
In previous articles, we explored the biological complexity of African swine fever virus (ASFV) and the immune responses it triggers in pigs. These insights highlight why African swine fever (ASF) remains such a difficult disease to control and why traditional vaccine approaches have so far fallen short.
Building on this scientific understanding, the VAX4ASF project is now addressing a key question: how can we translate knowledge of ASFV and host immunity into safe, effective and practical vaccines?
From virus biology to vaccine design
ASFV is far from a straightforward vaccine target. Its large and complex genome encodes numerous proteins involved in virus replication and immune evasion, allowing the virus to interfere with innate immune pathways and delay or suppress protective responses. Effective protection against ASF is thought to require a carefully balanced activation of both innate and adaptive immunity.
This balance is difficult to achieve with conventional vaccine platforms. Inactivated and subunit vaccines have generally failed to induce sufficient protection, while live attenuated vaccines (LAVs), although more immunogenic, raise significant safety concerns. These include the risk of residual virulence, genetic instability or unintended virus spread.
The scientific challenge, therefore, is to preserve the strong immune stimulation of live vaccines while eliminating their safety risks.
VAX4ASF integrates detailed studies of host–virus interactions, immune modulation and cross-protective antigens to inform rational vaccine engineering.
Limited-replication vaccines: a change in paradigm
VAX4ASF is exploring vaccine candidates designed to restrict viral replication in vaccinated animals while preserving key immunogenic properties of the virus.
These limited-replication approaches are designed to combine the immune stimulation of live vaccines with enhanced safety profiles.
Rather than allowing unrestricted viral replication in vivo, these strategies rely on precise genetic modifications intended to limit completion of the viral life cycle, while maintaining sufficient antigen expression to trigger protective immune responses.
Using immunology to guide vaccine optimisation
The design of these next-generation vaccines is not based on trial and error alone. VAX4ASF integrates detailed studies of host–virus interactions, immune modulation and cross-protective antigens to inform rational vaccine engineering.
By identifying ASFV genes that interfere with innate immune responses or contribute to immune evasion, researchers can determine which genes should be removed or modified in vaccine candidates. Similarly, understanding which viral antigens are associated with protective immunity helps prioritise their inclusion in vaccine designs.
This close interaction between fundamental research and applied vaccine development is a defining feature of the VAX4ASF innovation pathway.
Beyond vaccines: diagnostics and control strategies
In addition to vaccines, to better control ASF, VAX4ASF also aims to develop DIVA tests (Differentiating Infected from Vaccinated Animals), which are essential for disease surveillance in vaccinated populations. These diagnostic tools will allow authorities to monitor virus circulation and support informed decision-making.
In addition, epidemiological modelling within the project explores how vaccination could be integrated into broader ASF control strategies, including in domestic pig farms and at the wildlife–livestock interface.
Advancing ASF prevention through innovation
By combining advanced virology, immunology, vaccine engineering and disease modelling, VAX4ASF aims to deliver a new generation of ASF vaccines that are scientifically sound and practically viable.
This article marks the next step in the VAX4ASF knowledge journey: moving from understanding the virus and the immune response towards designing innovative solutions that could transform how ASF is prevented and controlled in the future.