Transiently produced IgGs enable infection-blocking vaccine efficacy assessment

Abstract Many vaccines are evaluated based on their ability to prevent symptoms, rather than infection itself, limiting their effectiveness in controlling asymptomatic transmission and achieving viral eradication. Here, we aimed to develop a serology-based strategy to detect asymptomatic infections and quantify the duration of infection-blocking protection, thereby enabling data-driven re-vaccination and offering a complementary framework for future infection-blocking VE evaluation. Using porcine circovirus 2 vaccines as a model, we identified that anti-peptide IgGs appear transiently after vaccination but are reproducibly re-induced upon post-vaccination infection, whereas anti-Capsid protein IgGs persist over time. This distinct serological response enables detection of new infections post-vaccination. By analyzing anti-peptide IgG response patterns across multiple sampling time points, we defined a digital microarray index (DMI) that captured the duration of vaccine-induced protection, and successfully ranked the infection-blocking efficacy of five commercial vaccines. Application to single-day samples from eight farms demonstrated that DMI, when paired with vaccination timing, accurately determined herd-level immune status and informed rational re-vaccination scheduling. This study introduces a serological platform for detecting asymptomatic infections and quantifying infection-blocking protection. The DMI enables high-resolution immune surveillance, informs timely re-vaccination, and lays the groundwork for future VE trials targeting infection-blocking and pathogen elimination.