LB11. A Single Dose of the MVA-BN Smallpox Vaccine Induces an Early Protective Antibody Response Similar to a Traditional Replicating Vaccine and Is Suitable for Emergency Scenarios

BACKGROUND: Smallpox remains a high-priority threat due to its potential for re-emergence through events including bioterrorism and spontaneous mutation. While traditional replicating smallpox vaccines such as ACAM2000 are associated with serious side effects, the non-replicating MVA BN smallpox vaccine was developed as a safer alternative. METHODS: This phase 3 non-inferiority study compared indicators of efficacy between the MVA-BN smallpox vaccine and ACAM2000. The co-primary endpoints were (1) to compare vaccine-induced serum neutralizing antibodies (geometric mean titer [GMT]) at predefined Peak Visits, as measured by plaque reduction neutralization tests (PRNT) and (2) to assess the attenuation of ACAM2000-induced takes after MVA-BN administration by measuring maximum lesion area (MLA). Early neutralizing antibody GMTs at Day 14, a timepoint considered protective for traditional replicating smallpox vaccines, were also compared following single doses of either vaccine. RESULTS: A total of 440 subjects were evenly randomized to receive either 2 doses of MVA-BN followed by 1 dose of ACAM2000 at 4 week intervals (Group 1) or a single dose of ACAM2000 (Group 2). Peak neutralizing antibody GMTs were significantly higher following 2 MVA-BN doses (153.5) compared with ACAM2000 (79.3), with a ratio of 1.935 (95% CI: 1.562, 2.397). At Day 14, neutralizing antibody GMTs were equal following a single dose of either MVA BN or ACAM2000 (16.2, ratio of 0.997, 95% CI: 0.738, 1.348), with similar seroconversion rates (90.8% vs. 91.8%, respectively). The median MLA induced by ACAM2000 was significantly reduced when subjects received prior MVA-BN in Group 1 (0 mm(2)) compared with Group 2 (76.0 mm(2)), suggesting protection against orthopoxvirus. MVA BN was well tolerated, demonstrating a better safety profile than ACAM2000. CONCLUSION: Two doses of MVA-BN induce significantly higher peak neutralizing antibody responses compared with ACAM2000. A single dose induces an early neutralizing antibody response equal to ACAM2000 at Day 14, demonstrating the suitability of MVA BN in both pre- and post-outbreak scenarios. This study was partly funded by BARDA under contract HHSO100200700034C. DISCLOSURES: Jane Maclennan, BSc MRPharmS, Bavarian Nordic (Employee), Bavarian Nordic (Employee, Shareholder), Heinz Weidenthaler, MD, Bavarian Nordic (Employee, Shareholder), Phillip Pittman, MD, Bavarian Nordic (Scientific Research Study Investigator), Darja Schmidt, PhD, Bavarian Nordic (Employee, Shareholder), Paul Chaplin, PhD, Bavarian Nordic (Board Member, Employee, Shareholder), Bavarian Nordic (Employee, Shareholder).