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Low Dose Monkeypox Vaccine
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The demonstration of immunogenic non-inferiority (and superiority in 3 of the 4 immunogenicity assays) and safety equivalence of the lyophilized formulation compared to the liquid formulation provides bridging data for the transition from a liquid to a lyophilized formulation of IMVAMUNE®. Additionally, the ID route provided an equivalent immune response to the SC route using 80% less antigen. This antigen sparing effect could significantly increase the number of vaccine doses available in the event of an emergency by 5-fold. Although the ID route had increased local reactogenicity events, the lack of clinical significance of these events makes the route suitable in an emergency situation.
Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naïve subjects
Highlights
• Lyophilized MVA was more immunogenic than the current liquid formulation of MVA.
• The lower ID dose of MVA was immunologically non-inferior to the standard SC dose.
• The ID route resulted in more erythema and/or induration than the SC route.
• The ID route may increase the number of available doses in an emergency situation.
Abstract
Background
Modified vaccinia Ankara (MVA) is being developed as a safer smallpox vaccine and is being placed in the US Strategic National Stockpile (SNS) as a liquid formulation for subcutaneous (SC) administration at a dose of 1 x 108 TCID50 in a volume of 0.5 mL. This study compared the safety and immunogenicity of the standard formulation, dose and route with both a more stable, lyophilized formulation and with an antigen-sparing intradermal (ID) route of administration.
Methods
524 subjects were randomized to receive either a full dose of Lyophilized-SC, a full dose of Liquid-SC or 20% (2 x 107 TCID50 in 0.1 mL) of a full dose Liquid-ID MVA on Days 0 and 28. Safety and immunogenicity were followed through 180 days post second vaccination.
Results
Among the 3 groups, the proportion of subjects with moderate/severe functional local reactions was significantly different (P = 0.0013) between the Lyophilized-SC group (30.3%), the Liquid-SC group (13.8%) and Liquid-ID group (22.0%) only after first vaccination; and for moderate/severe measured erythema and/or induration after any vaccination (P = 0.0001) between the Lyophilized-SC group (58.2%), the Liquid-SC group (58.1%) and the Liquid-ID group (94.8%) and the reactions lasted longer in the Liquid-ID group. In the ID Group, 36.1% of subjects had mild injection site skin discoloration lasting ≥6 months.
After second vaccination Day (42-208), geometric mean of peak neutralization titers were 87.8, 49.5 and 59.5 for the Lyophilized-SC, Liquid-SC and Liquid-ID groups, respectively, and the maximum number of responders based on peak titer in each group was 142/145 (97.9%), 142/149 (95.3%) and 138/146 (94.5%), respectively. At 180 days after the second vaccination, geometric mean neutralization titers declined to 11.7, 10.2 and 10.4 with only 54.3%, 39.2% and 35.2% of subjects remaining seropositive for the Lyophilized-SC, Liquid-SC and Liquid-ID groups, respectively. Both the Lyophilized-SC and Liquid-ID groups were considered non-inferior (primary objective) to the Liquid-SC group.
Conclusions
Transitioning to a lyophilized formulation, which has a longer shelf life, will not negatively impact immunogenicity. In a situation where insufficient vaccine is available, ID vaccination could be used, increasing the number of available doses of vaccine in the SNS 5-fold (i.e., from 20 million to 100 million doses).
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