ASFV vaccine protection correlates with early IFN-α, antigen presentation, and memory T-cell responses in pigs

African swine fever virus (ASFV) causes a highly fatal hemorrhagic disease in domestic pigs and wild boars, posing severe threats to the global pork industry. Current live attenuated vaccines (LAVs) face significant safety challenges due to a narrow margin between efficacy and residual virulence. Understanding the specific immune responses that confer protection versus those that are detrimental is a critical knowledge gap in developing safer and more effective ASFV vaccines. This study aimed to identify innate and adaptive immune correlates of protection against ASFV.

Researchers utilized an established pig model, comparing two groups: farm pigs and specific pathogen-free (SPF) pigs, differing in baseline immunological status. Animals were immunized with an attenuated ASFV strain and subsequently challenged with a related, highly virulent genotype II ASFV strain. A systems immunology approach correlated kinetic data, including serum cytokines, blood transcription modules (BTMs), T-cell responses, and antibody levels, with clinical outcomes to track immune responses over time.

Key innate correlates of protection included an early and sustained IFN-α response, activation of antigen presentation BTMs, and controlled IL-8 levels during immunization. Lower baseline immune activation observed in SPF pigs was linked to increased protection. Adaptive correlates encompassed cell cycle, plasma cell, and T-cell BTM responses lasting until day 15 post-immunization. An effective response from ASFV-specific Th cells prior to challenge indicated protection.

After challenge, an early IFN-α response, low levels of pro-inflammatory cytokines, and strong induction of memory Th and Tc cells correlated with improved clinical outcomes. This comprehensive model highlights the critical role of host-specific factors in vaccine efficacy.