Ancient Chinese variolation represents the world′s earliest practice of disease prevention through vaccination. Its theoretical foundation lies in the traditional Chinese medicine (TCM) hypothesis of smallpox pathogenesis, which posits that "external pathogens trigger fetal toxins." Through the lens of modern vaccinology, this paper analyzes the scientific rationale of this traditional immunization method. Key aspects examined include the use of pox scabs as vaccines, nasal inoculation, passage attenuation for vaccine preparation, and TCM′s understanding of smallpox pathogenesis. The paper also addresses the historical limitations of variolation, including uncontrollable viral activity and load, safety risks posed by strong immune responses that could occur, and insufficient vaccination accessibility.

Ancient Chinese variolation represents the world′s earliest practice of disease prevention through vaccination. Its theoretical foundation lies in the traditional Chinese medicine (TCM) hypothesis of smallpox pathogenesis, which posits that "external pathogens trigger fetal toxins." Through the lens of modern vaccinology, this paper analyzes the scientific rationale of this traditional immunization method. Key aspects examined include the use of pox scabs as vaccines, nasal inoculation, passage attenuation for vaccine preparation, and TCM′s understanding of smallpox pathogenesis. The paper also addresses the historical limitations of variolation, including uncontrollable viral activity and load, safety risks posed by strong immune responses that could occur, and insufficient vaccination accessibility.