Equivalence of Freeze-dried and Liquid-frozen Formulations of MVA-BN as Smallpox and Mpox Vaccine

Abstract

AbstractOrthopox virus-induced diseases such as smallpox and mpox (also known as monkeypox previously) remain a serious public health concern. Modified Vaccinia Ankara Bavarian Nordic (MVA-BN) has been approved in its liquid-frozen (LF) formulation for prevention of smallpox and mpox in the US, Canada and EU. A freeze-dried (FD) formulation might confer additional benefits such as longer shelf life and less reliance on cold chain storage and transport, thus can better meet the potential challenge of large quantity vaccine deployment in emergency situations.In a phase 2 clinical trial, 651 vaccinia-naïve participants were vaccinated with two doses of MVA-BN LF or FD, 4 weeks apart. The objectives were to compare MVA-BN FD with LF in terms of vaccine-induced immune responses, safety and reactogenicity.Strong vaccinia-specific humoral and cellular immune responses were induced by both formulations, with peak humoral responses at Week 6 and peak cellular responses at Week 2. At Week 6, geometric means of total antibody titers were 1096 (95% CI 1013, 1186) from the FD group and 877 (95% CI 804, 956) from the LF group, achieving the primary endpoint of non-inferiority of MVA-BN FD compared to MVA-BN LF. At Week 2, geometric means of T cell spot forming units were 449 (95% CI 341, 590) from the FD group and 316 (95% CI 234, 427) from the LF group. Both formulations of MVA-BN were well tolerated, with similar unsolicited AEs and solicited systemic reactions in both groups but slightly higher local reactions in the FD group. No vaccine related serious adverse events (SAEs) or vaccine related AE of special interest were reported.The FD formulation of MVA-BN was shown to be equivalent to the LF formulation in immunogenicity, and comparable safety findings were observed from both formulations.Clinical Trial Registration:NCT01668537HighlightsEquivalence of MVA-BN freeze-dried and liquid-frozen formulations in immunogenicity MVA-BN FD and MVA-BN LF are comparable in clinical safety and reactogenicity Peak T cell responses were observed 2 weeks after the first vaccination