title: Safety and immunogenicity of an intranasal Shigella flexneri 2a Invaplex 50 vaccine.
abstract: BACKGROUND
  Shigella flexneri 2a lipopolysaccharide 50 is a nasally delivered subunit vaccine consisting of a macromolecular complex composed of LPS, IpaB, IpaC and IpaD. The current study examined vaccine safety and immunogenicity across a dose range and the clinical performance of a new intranasal delivery device.
  
  
  METHODS
  Volunteers (N=36) were randomized to receive vaccine via the Dolphin™ (Valois of America, Congers, New York) intranasal spray device at one of three doses (240, 480, and 690 μg) on days 0, 14, and 28. Another group (N=8) received the 240 μg dose via pipette. Vaccine safety was actively monitored and antigen-specific humoral and mucosal immune responses were determined.
  
  
  RESULTS
  There were no serious adverse events and the majority of adverse events (98%) were mild. Antibody secreting cells (ASC), plasma, and mucosal immune responses to Shigella antigens were detected at all three dose levels with the 690 μg dose inducing the highest magnitude and frequency of responses. Vaccination with comparable doses of Invaplex 50 via the Dolphin™ resulted in higher plasma and ASC immune responses as compared to pipette delivery.
  
  
  CONCLUSIONS
  In this trial the S. flexneri 2a Invaplex 50 vaccine was safe, well-tolerated and induced robust levels of antigen-specific intestinal IgA and ASC responses. The spray device performed well and offered an advantage over pipette intranasal delivery.
authors.affiliation: Naval Medical Research Center, Silver Spring, MD, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Riddle
authors.forename: Robert W
authors.initials: RW
authors.lastname: Kaminski
authors.forename: Carlos
authors.initials: C
authors.lastname: Williams
authors.forename: Chad
authors.initials: C
authors.lastname: Porter
authors.forename: Shahida
authors.initials: S
authors.lastname: Baqar
authors.forename: Alexis
authors.initials: A
authors.lastname: Kordis
authors.forename: Theron
authors.initials: T
authors.lastname: Gilliland
authors.forename: Joyce
authors.initials: J
authors.lastname: Lapa
authors.forename: Melissa
authors.initials: M
authors.lastname: Coughlin
authors.forename: Chris
authors.initials: C
authors.lastname: Soltis
authors.forename: Erica
authors.initials: E
authors.lastname: Jones
authors.forename: Jackie
authors.initials: J
authors.lastname: Saunders
authors.forename: Paul B
authors.initials: PB
authors.lastname: Keiser
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Ranallo
authors.forename: Robert
authors.initials: R
authors.lastname: Gormley
authors.forename: Michael
authors.initials: M
authors.lastname: Nelson
authors.forename: K Ross
authors.initials: KR
authors.lastname: Turbyfill
authors.forename: David
authors.initials: D
authors.lastname: Tribble
authors.forename: Edwin V
authors.initials: EV
authors.lastname: Oaks
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D000921:Antibody-Producing Cells / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D004311:Double-Blind Method; D004333:Drug Administration Routes; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology*; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D059085:Nasal Sprays; D022281:Shigella Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D012763:Shigella flexneri / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D059085:Nasal Sprays; D022281:Shigella Vaccines