title: Safety and immunogenicity of a modified vaccinia Ankara vaccine using three immunization schedules and two modes of delivery: A randomized clinical non-inferiority trial.
abstract: To guide the use of modified vaccinia Ankara (MVA) vaccine in response to a release of smallpox virus, the immunogenicity and safety of shorter vaccination intervals, and administration by jet injector (JI), were compared to the standard schedule of administration on Days 1 and 29 by syringe and needle (S&N).
  
  
  
  Healthy adults 18-40years of age were randomly assigned to receive MVA vaccine subcutaneously by S&N on Days 1 and 29 (standard), Days 1 and 15, or Days 1 and 22, or to receive the vaccine subcutaneously by JI on Days 1 and 29. Blood was collected at four time points after the second vaccination for plaque reduction neutralization test (PRNT) (primary endpoint) and ELISA (secondary endpoint) antibody assays. For each subject, the peak PRNT (or ELISA) titer was defined by the highest PRNT (or ELISA) titer among all available measurements post second vaccination. Non-inferiority of a non-standard arm compared to the standard arm was met if the upper limit of the 98.33% confidence interval of the difference in the mean log2peak titers between the standard and non-standard arm was less than 1.
  
  
  
  Non-inferiority of the PRNT antibody response was not established for any of the three non-standard study arms. Non-inferiority of the ELISA antibody response was established for the Day 1 and 22 compressed schedule and for administration by JI. Solicited local reactions, such as redness and swelling, tended to be more commonly reported with JI administration. Four post-vaccination hypersensitivity reactions were observed.
  
  
  
  Evaluations of the primary endpoint of PRNT antibody responses do not support alternative strategies of administering MVA vaccine by S&N on compressed schedules or administration by JI on the standard schedule.
  
  
  
  clinicaltrials.gov Identifier: NCT01827371.
authors.affiliation: Group Health Research Institute, Seattle, WA, United States. Electronic address: Jackson.L@ghc.org.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Jackson
authors.affiliation: Division of Infectious Diseases, Allergy, & Immunology, Saint Louis University School of Medicine, St. Louis, MO, United States.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Frey
authors.affiliation: Departments of Molecular Virology & Microbiology and Medicine, Baylor College of Medicine, Houston, TX, United States.
authors.forename: Hana M
authors.initials: HM
authors.lastname: El Sahly
authors.affiliation: The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Decatur, GA, United States.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Mulligan
authors.affiliation: University of Iowa and Iowa City VA Medical Center, Iowa City, IA, United States.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Winokur
authors.affiliation: Division of Infectious Disease and Tropical Pediatrics, Department of Pediatrics, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, United States.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Kotloff
authors.affiliation: Division of Infectious Disease and Tropical Pediatrics, Department of Pediatrics, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, United States.
authors.forename: James D
authors.initials: JD
authors.lastname: Campbell
authors.affiliation: Departments of Molecular Virology & Microbiology and Medicine, Baylor College of Medicine, Houston, TX, United States.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Atmar
authors.affiliation: Division of Infectious Diseases, Allergy, & Immunology, Saint Louis University School of Medicine, St. Louis, MO, United States.
authors.forename: Irene
authors.initials: I
authors.lastname: Graham
authors.affiliation: Emory Children's Center, Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA, United States.
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Anderson
authors.affiliation: Division of Infectious Diseases, Allergy, & Immunology, Saint Louis University School of Medicine, St. Louis, MO, United States.
authors.forename: Edwin L
authors.initials: EL
authors.lastname: Anderson
authors.affiliation: Departments of Molecular Virology & Microbiology and Medicine, Baylor College of Medicine, Houston, TX, United States.
authors.forename: Shital M
authors.initials: SM
authors.lastname: Patel
authors.affiliation: Group Health Research Institute, Seattle, WA, United States.
authors.forename: Colin
authors.initials: C
authors.lastname: Fields
authors.affiliation: Departments of Molecular Virology & Microbiology and Medicine, Baylor College of Medicine, Houston, TX, United States.
authors.forename: Wendy
authors.initials: W
authors.lastname: Keitel
authors.affiliation: The Hope Clinic of the Emory Vaccine Center, Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Decatur, GA, United States.
authors.forename: Nadine
authors.initials: N
authors.lastname: Rouphael
authors.affiliation: The Emmes Corporation, Rockville, MD, United States.
authors.forename: Heather
authors.initials: H
authors.lastname: Hill
authors.affiliation: The Emmes Corporation, Rockville, MD, United States.
authors.forename: Johannes B
authors.initials: JB
authors.lastname: Goll
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D000074099:Equivalence Trials as Topic; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007115:Immunization Schedule; D007279:Injections, Subcutaneous; D008297:Male; D009500:Neutralization Tests; D012900:Smallpox Vaccine / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology*; D010948:Viral Plaque Assay; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004337:Drug Carriers; D012900:Smallpox Vaccine
keywords: Hypersensitivity reaction; Jet injector; PRNT; Smallpox; Vaccine; Vaccinia