Abstract

Compared with inactivated vaccines, live attenuated vaccines can theoretically induce potent cellular and humoral responses through both exogenous and endogenous antigen-presentation pathways. However, the percentage of live virus particles in the final vaccine products can vary between manufacturers, potentially due to variations in production processes such as lysis and purification. Whether the live-to-dead viral particles ratio influences the resulting immune response pattern remains unclear. To address this question, we formulated varicella vaccines (VarV) mimicking high-viability and low-viability compositions and systematically analyzed the immune response they induced in mice. Surprisingly, the percentage of viable viral particles in VarV products appears to modulate immune polarization. Higher viability tended to be associated with stronger Th1-oriented cellular responses and more robust humoral immunity, contributing to an overall immune profile resembling that induced by endogenous antigen presentation. This finding supports incorporating virus viability into VarV quality control, in addition to conventional viral titers, to optimize vaccine-induced cellular immunity and long-term protection against VZV reactivation.