{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:32:18Z","timestamp":1787315538104,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PT. Bio Farma","award":["007.30\/PGD\/VII\/2024"],"award-info":[{"award-number":["007.30\/PGD\/VII\/2024"]}]},{"name":"PT. Bio Farma","award":["PO\/BIOF\/2024\/2996"],"award-info":[{"award-number":["PO\/BIOF\/2024\/2996"]}]},{"name":"PT. Bio Farma","award":["PO-00048782"],"award-info":[{"award-number":["PO-00048782"]}]},{"name":"PT. Bio Farma","award":["342\/AIRC-Ind\/Ext-B\/2024"],"award-info":[{"award-number":["342\/AIRC-Ind\/Ext-B\/2024"]}]},{"name":"PMDSU Scholarship Program","award":["VIII"],"award-info":[{"award-number":["VIII"]}]},{"name":"Directorate General of Higher Education, Ministry of Education and Culture of the Republic of Indonesia","award":["2158\/E4\/DT.04.02\/2024"],"award-info":[{"award-number":["2158\/E4\/DT.04.02\/2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>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 &gt; 0.05). AST differences (p &lt; 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 &gt; 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.<\/jats:p>","DOI":"10.3390\/vaccines14010094","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T09:24:34Z","timestamp":1768901074000},"page":"94","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Liver Safety Assessment of an Indonesian Hexavalent Vaccine Candidate Through Histopathology and ALT\/AST Evaluation in Rats and Rabbits"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2366-4562","authenticated-orcid":false,"given":"Elisa D.","family":"Pratiwi","sequence":"first","affiliation":[{"name":"Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya 60115, Indonesia"},{"name":"Professor Nidom Foundation, Surabaya 60236, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiza W.","family":"Mawaddah","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya 60115, Indonesia"},{"name":"Professor Nidom Foundation, Surabaya 60236, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arif R.","family":"Sadjuri","sequence":"additional","affiliation":[{"name":"PT Bio Farma, Bandung 40161, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimas T.","family":"Nugroho","sequence":"additional","affiliation":[{"name":"PT Bio Farma, Bandung 40161, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7023-0518","authenticated-orcid":false,"given":"Arip","family":"Hidayat","sequence":"additional","affiliation":[{"name":"PT Bio Farma, Bandung 40161, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2997-8681","authenticated-orcid":false,"given":"Astria N.","family":"Nidom","sequence":"additional","affiliation":[{"name":"Professor Nidom Foundation, Surabaya 60236, Indonesia"},{"name":"Faculty of Medicine, Universitas Airlangga, Surabaya 60132, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zakiyyan I.","family":"Ayyuba","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya 60115, Indonesia"},{"name":"Professor Nidom Foundation, Surabaya 60236, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eka S.","family":"Wahyuningsih","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya 60115, Indonesia"},{"name":"Global Biosains Teknologi, Malang 65145, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9561-1984","authenticated-orcid":false,"given":"Kuncoro P.","family":"Santoso","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya 60115, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani","family":"Plumeriastuti","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya 60115, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Soeharsono","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya 60115, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3685-6981","authenticated-orcid":false,"given":"Setyarina","family":"Indrasari","sequence":"additional","affiliation":[{"name":"Professor Nidom Foundation, Surabaya 60236, Indonesia"},{"name":"Global Biosains Teknologi, Malang 65145, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1433-6026","authenticated-orcid":false,"given":"Reviany V.","family":"Nidom","sequence":"additional","affiliation":[{"name":"Professor Nidom Foundation, Surabaya 60236, Indonesia"},{"name":"Global Biosains Teknologi, Malang 65145, Indonesia"},{"name":"Riset AIRC Indonesia, Surabaya 60236, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1104-9259","authenticated-orcid":false,"given":"Acep R.","family":"Wijayadikusumah","sequence":"additional","affiliation":[{"name":"PT Bio Farma, Bandung 40161, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8106-0763","authenticated-orcid":false,"given":"Chairul A.","family":"Nidom","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary 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