Repeated-dose toxicity and immunogenicity evaluation of norovirus P particle-based rotavirus vaccine in juvenile cynomolgus monkeys.

Introduction: Rotavirus remains a major cause of mortality among young children worldwide, underscoring the urgent need for new vaccines. The present study evaluated the repeated-dose toxicity and immunogenicity of a bivalent rotavirus subunit candidate vaccine PP-P[6]/P[8]-VP8 Mix (containing equal amounts of P[6]-VP8 and P[8]-VP8 chimeric antigens) based on norovirus P particles in cynomolgus monkeys. Methods: The monkeys (5 per sex per group) were randomly assigned to a blank control group, an adjuvant control group, and low- and high-dose vaccine groups (60 μg/monkey and 120 μg/monkey). The animals received four intramuscular injections at 4-week intervals, followed by a 6-week recovery period. General behavior, body temperature, body weight, food intake, hematology, serum biochemistry, ophthalmic examination, electrocardiogram, urine analysis, immunogenicity parameters, and pathological examination of the animals were detected. Results: No toxicologically significant abnormalities were observed throughout the study. Histopathological examination showed that there were deposition foci of aluminum hydroxide adjuvant and mild subacute inflammatory reactions at the injection site in the vaccine group. Lymphoid follicle hyperplasia and lymph sinus histiocytosis were observed in the draining lymph nodes, which are typical local immune response manifestations of aluminum adjuvant vaccines. No other adverse pathological changes were found. Conclusions: Our regulatory toxicology study has demonstrated the safety and immunogenicity of PP-P[6]/P[8] - VP8 Mix under the experimental conditions, supporting its entry into clinical research.