Safety and immunogenicity of IMVAMUNE registered smallpox vaccine using different strategies for a post event scenario

• Published in: Vaccine 2013-06, Vol.31 (29), p.3025-3033
• Main Authors: Frey, Sharon E, Winokur, Patricia L, Salata, Robert A, El-Kamary, Samer S, Turley, Christine B, Walter, Emmanuel B, Hay, Christine Mhorag, Newman, Frances K, Hill, Heather R, Zhang, Ying, Chaplin, Paul, Tary-Lehmann, Magdalena, Belshe, Robert B
• Format: Article
• Language: English
• Subjects: Antibodies; Variola
• ISSN: 0264-410X
• DOI: 10.1016/j.vaccine.2013.04.050

Introduction: Reintroduction of Variola major as an agent of bioterrorism remains a concern. A shortened dosing schedule of Bavarian Nordic's (BN) IMVAMUNE registered (modified vaccinia Ankara vaccine against smallpox) was compared to the currently recommended 0- and 28-day schedule for non-inferiority by evaluating the magnitude and kinetics of the immune responses. Methods: Subjects were assigned to receive IMVAMUNE or placebo administered subcutaneously on Days 0 and 7, Days 0 and 28, or Day 0. Blood was collected for antibody and cell-mediated immune assays. Subjects were followed for safety for 12 months after last vaccination. Results: The primary endpoi nt of this study was the geometric mean antibody titers (GMT) at 14 days post last vaccination. Of 208 subjects enrolled, 191 received vaccine (Group: 0 + 7, Group: 0 + 28 and Group: 0) and 17 received placebo. Moderate/severe systemic reactogenicity after any vaccination were reported by 31.1%, 25.4%, and 28.6% of the subjects for Group: 0 + 7, Group: 0 + 28, and Group: 0, respectively (Chi-square test, P = 0.77). Based on BN's Plaque Reduction Assay GMTs, Group: 0 + 7 was non-inferior to Group: 0 + 28 at Day 4, 180, and 365 after the second vaccination. On Day 14, Group: 0 + 7 and Group: 0 + 28 GMT were 10.8 (CI: 9.0, 12.9) and 30.2 (CI: 22.1, 41.1), respectively. Based on BN's Enzyme-linked immunosorbent assay, the proportion of subjects with positive titers for Group: 0 + 28 was significantly greater than that for Group: 0 + 7 after second vaccination at Days 4 and 180. By Day 14 after the second dose, the IFN- gamma enzyme-linked immunosorbent spot (ELISPOT) responses were similar for Group: 0 + 28 and Group: 0 + 7. Conclusion: Overall, a standard dose of IMVAMUNE (0.5 mL of 1 x 10 super(8)TCID/mL) administered subcutaneously was safe and well tolerated. A second dose of IMVAMUNE at Day 28 compared to Day 7 provided greater antibody responses and the maximal number of responders. By Day 14 after the second dose, IFN- gamma ELISPOT responses were similar for Group: 0 + 28 and Group: 0 + 7.