Pratiwi, Elisa D. and Mawaddah, Tiza W. and Sadjuri, Arif R. and Nugroho, Dimas T. and Hidayat, Arip and Nidom, Astria N. and Ayyuba, Zakiyyan I. and Wahyuningsih, Eka S. and Santoso, Kuncoro P. and Plumeriastuti, Hani and Soeharsono and Indrasari, Setyarina and Nidom, Reviany V. and Wijayadikusumah, Acep R. and Nidom, Chairul A. (2026) Liver Safety Assessment of an Indonesian Hexavalent Vaccine Candidate Through Histopathology and ALT/AST Evaluation in Rats and Rabbits. Vaccines, 14 (1).

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Abstract

Background: Administering several separate childhood vaccines can reduce adherence to immunization schedules due to missed appointments and the burden of repeated injections. A hexavalent formulation targeting diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type B, and poliovirus offers a practical approach to improve compliance and streamline immunization. Methods: Toxicity testing was performed in Wistar rats and New Zealand White rabbits (60 rats and 30 rabbits). Animals were distributed into three groups: hexavalent vaccine + low-dose sIPV, hexavalent vaccine + high-dose sIPV, and control. Each animal received a 0.5 mL intramuscular injection at weeks 0, 4, 8, and 12. Clinical observations were conducted throughout the study. Serum samples were collected one day before each injection and at the endpoint, while liver tissue was collected at the endpoint. ALT and AST concentrations were analyzed using an automated analyzer, and hepatic morphology was evaluated microscopically. Results: No abnormal clinical signs related to vaccination were observed. ALT concentrations showed no significant differences (p > 0.05). AST differences (p < 0.05) were detected between the high-dose group and the control on day 27 in female rabbits and on day 83 in female rats; however, all values remained within normal physiological limits. Histopathological examination revealed no irreversible hepatic lesions, including hydropic degeneration, portal inflammation, focal necrosis, or connective tissue proliferation, and no significant differences were noted (p > 0.05). Conclusions: Repeated administration of the hexavalent vaccine candidate at low and high doses produced no toxicological effects in animal models, supporting its safety for further clinical development. © 2026 by the authors.

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