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Background: Meningococcal vaccines are licensed to prevent invasive meningococcal disease (IMD) caused by serogroups ACWY and B; however, they are generally available as separate formulations. MenACWY-7B is an investigational pentavalent vaccine candidate designed to address IMD caused by the major serogroups in a single formulation and to broaden MenB strain coverage through inclusion of additional MenB antigens. Aim: To describe the preclinical proof-of-concept package supporting advancement of MenACWY-7B from nonclinical comparability and formulation selection to readiness for first-in-human evaluation in a Phase I/II clinical study. Results: In rabbit and rat models, functional immunogenicity of the MenB and MenACWY components was maintained when combined in MenACWY-7B, as assessed by human serum bactericidal activity (hSBA) against established indicator strains. Breadth of MenB strain coverage was evaluated using a diverse MenB strain panel, and MenACWY-7B showed broader bactericidal activity than the MenB comparator across the tested strains. Dose-ranging experiments showed no advantage of the highest dosage, with no substantial differences between lower and intermediate dosages in immunogenicity or breadth of coverage. Additional analyses confirmed that the glycoconjugate antigens retained the capacity to induce binding antibody responses (total IgG by ELISA) and functional bactericidal activity. Conclusions: This preclinical proof-of-concept data package provides a translational bridge from animal models to clinical evaluation, supporting formulation selection and progression of MenACWY-7B into a Phase I/II clinical study. |