Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), is characterized by its high contagiousness. The COVID-19 pandemic has exerted profound impacts on human society. The persistent circulation of SARS-CoV-2 in human populations continues to pose re-exposure risks for both vaccinated individuals and those with prior natural infection. Against this epidemiological background, there is an urgent need to characterize the transmission dynamics of SARS-CoV-2 in the context of pre-existing immunity. Using a ferret infection model, this study systematically addresses critical scientific questions, including viral transmission efficiency, temporal patterns of transmissibility, and the ability of pre-existing immunity to mitigate reinfection and viral shedding. The findings provide robust experimental evidence for elucidating the transmission mechanisms of SARS-CoV-2 and offer scientific insights to inform the rational design of optimized antiviral strategies.IMPORTANCEIn this study, a ferret infection model was used to systematically investigate SARS-CoV-2's in vivo transmission dynamics and modes with pre-existing immunity. By characterizing viral transmission efficiency, temporal shedding patterns, and immunity's role in mitigating re-infection severity and dissemination, it provides direct evidence for understanding SARS-CoV-2 spread in immune-exposed hosts. It quantifies how humoral immunity modulates viral load (primary/secondary infections) and ferret contact transmission. Findings establish a key SARS-CoV-2 transmission framework-pre-existing immunity shortens shedding, reduces secondary attack rates but retains residual transmissibility-fill knowledge gaps, guide vaccine/herd immunity/public health measures, and lay a foundation for predicting real-world transmission and antiviral policies via integrated endpoints.

Keywords: SARS-CoV-2; pre-existing immunity; transmission.