Abstract
Background: A quadrivalent HPV vaccine (BPV) has been developed to prevent diseases caused by HPV types 6, 11, 16, and 18 for the first time in Iran. The BPV is composed of the papillomavirus major capsid protein L1, which serves as the primary target in the design of the prophylactic HPV vaccines. To enhance immunogenicity, BPV was formulated with an amorphous aluminum hydroxy phosphate sulfate adjuvant. Methods: The immunogenicity and safety of BPV were assessed through analyses of both humoral and cell-mediated immunity, single and repeated doses, and reproductive effects using animal models. Results: Acute toxicity assessments showed no abnormalities in ophthalmic examinations, biochemical profiles, hematological parameters, and gross pathology findings. Additionally, no mortality or abnormal clinical signs were observed during a 90-day repeated-dose toxicity study. While some inflammatory reactions were noted at the injection sites and in the liver tissues of BPV-treated groups, these reactions were resolved by day 90 after the initial BPV administration. Furthermore, no signs of toxicity were detected in F1 offspring, and no adverse effects were identified in maternal reproductive performance, fertility, or hematological or biochemical parameters throughout the study duration. The BPV candidate successfully induced T-cell proliferation and increased the proportions of CD(3)(+) CD(4)(+) and CD(3)(+) CD(8)(+) T cells. It also stimulated the secretion of both interferon gamma (IFN-γ) and interleukin-4 (IL-4) cytokines in splenocytes isolated from animal models after the third dose. Moreover, anti-HPV L1 IgG antibody production was confirmed on day 14 after administration of each of the three BPV vaccine doses. Conclusions: The findings suggest that BPV is a vaccine candidate that stimulates both cellular and humoral immunity and demonstrate its safety profile in animal models.