Immunogenicity and safety in animals of a lyophilized live attenuated hepatitis A vaccine following stabilizer optimization.

To evaluate the immunogenicity and safety profiles of lyophilized hepatitis A live attenuated vaccine (L-A-1 attenuated strain) after stabilizer formula optimization using non-human primates and various rodent models. Immunogenicity assessment was conducted using NIH mice and rhesus monkeys comparing pre-optimization commercial vaccine with post-optimization test vaccine. Mice received single immunizations with cardiac blood collection at day 28 for ELISA-based hepatitis A antibody detection. Non-human primates were monitored for clinical status, body weight, and hepatitis A virus IgG antibody titers at baseline(D0) and post-immunization timepoints (D14, D21, D28). Safety evaluation included guinea pig systemic anaphylaxis testing, rabbit subcutaneous irritation assessment, and rat single-dose toxicity investigation using both vaccine formulations and their corresponding stabilizer components. Both mouse and non-human primate studies demonstrated equivalent immunogenicity between optimized and commercial vaccines, with 100% seroconversion rates and comparable antibody concentrations (GMCs: 390.52 vs. 388.25 mIU/ml in mice, p > 0.05). Non-human primates showed 16-256 fold antibody titer increases by day 28 with normal clinical status maintained throughout. Safety assessments revealed no systemic sensitization, local irritation, or toxicity in any animal model for both formulations and their corresponding stabilizer components. Comprehensive animal model investigations demonstrate that the optimized stabilizer formulation maintains equivalent immunogenic potency while establishing a favorable safety profile comparable to the pre-optimization formulation. These findings provide substantive preclinical evidence supporting the feasibility and benefits of the stabilizer formula optimization strategy for lyophilized hepatitis A live attenuated vaccine.