title: Safety and immunogenicity of IMVAMUNE® smallpox vaccine using different strategies for a post event scenario.
abstract: BACKGROUND
  Reintroduction of Variola major as an agent of bioterrorism remains a concern. A shortened dosing schedule of Bavarian Nordic's (BN) IMVAMUNE(®) (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 endpoint 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-γ enzyme-linked immunosorbent spot (ELISPOT) responses were similar for Group: 0+28 and Group: 0+7.
  
  
  CONCLUSIONS
  Overall, a standard dose of IMVAMUNE (0.5 mL of 1 x 10(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-γ ELISPOT responses were similar for Group: 0+28 and Group: 0+7.
authors.affiliation: Division of Infectious Diseases, Allergy & Immunology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA. freyse@slu.edu
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Frey
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Winokur
authors.forename: Robert A
authors.initials: RA
authors.lastname: Salata
authors.forename: Samer S
authors.initials: SS
authors.lastname: El-Kamary
authors.forename: Christine B
authors.initials: CB
authors.lastname: Turley
authors.forename: Emmanuel B
authors.initials: EB
authors.lastname: Walter
authors.forename: Christine Mhorag
authors.initials: CM
authors.lastname: Hay
authors.forename: Frances K
authors.initials: FK
authors.lastname: Newman
authors.forename: Heather R
authors.initials: HR
authors.lastname: Hill
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Paul
authors.initials: P
authors.lastname: Chaplin
authors.forename: Magdalena
authors.initials: M
authors.lastname: Tary-Lehmann
authors.forename: Robert B
authors.initials: RB
authors.lastname: Belshe
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D023482:Bioterrorism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D008297:Male; D012899:Smallpox / Q000517:prevention & control*; D012900:Smallpox Vaccine / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D014611:Vaccination / Q000009:adverse effects / Q000379:methods; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D012901:Variola virus / Q000276:immunology; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D012900:Smallpox Vaccine; D014613:Vaccines, Attenuated; C527606:smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic