title: Safety and immunogenicity of a Shigella flexneri 2a Invaplex 50 intranasal vaccine in adult volunteers.
abstract: Shigellosis is a leading cause of diarrhea worldwide prompting vaccine development. The Shigella flexneri Invaplex 50 is a macromolecular complex containing IpaB, IpaC, and LPS, formulated from an aqueous extract of virulent Shigella delivered via nasal administration. Preclinical vaccine testing demonstrated safety, immunogenicity and efficacy. An open-label dose-escalating phase 1 study evaluated a 3-dose (2-week intervals) regimen via nasal pipette delivery. Thirty-two subjects were enrolled into one of four vaccine dose groups (10, 50, 240, or 480 microg). The vaccine was well tolerated with minor short-lived nasal symptoms without evidence of dose effect. Antibody-secreting cell (ASC) responses were elicited at doses > or =50 microg with the highest IgG ASC, Invaplex 50 (100%) and S. flexneri 2a LPS (71%), as well as, serologic responses (43%) occurring with the 240 microg dose. Fecal IgA responses, Invaplex 50 (38.5%) and LPS (30.8%), were observed at doses > or =240 microg. The Invaplex 50 nasal vaccine was safe with encouraging mucosal immune responses. Follow-on studies will optimize dose, delivery mechanism and assess efficacy in a S. flexneri 2a challenge study.
authors.affiliation: Naval Medical Research Center, Silver Spring, MD, USA. dtribble@usuhs.mil
authors.forename: D
authors.initials: D
authors.lastname: Tribble
authors.forename: R
authors.initials: R
authors.lastname: Kaminski
authors.forename: J
authors.initials: J
authors.lastname: Cantrell
authors.forename: M
authors.initials: M
authors.lastname: Nelson
authors.forename: C
authors.initials: C
authors.lastname: Porter
authors.forename: S
authors.initials: S
authors.lastname: Baqar
authors.forename: C
authors.initials: C
authors.lastname: Williams
authors.forename: R
authors.initials: R
authors.lastname: Arora
authors.forename: J
authors.initials: J
authors.lastname: Saunders
authors.forename: M
authors.initials: M
authors.lastname: Ananthakrishnan
authors.forename: J
authors.initials: J
authors.lastname: Sanders
authors.forename: G
authors.initials: G
authors.lastname: Zaucha
authors.forename: R
authors.initials: R
authors.lastname: Turbyfill
authors.forename: E
authors.initials: E
authors.lastname: Oaks
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000818:Animals; D000917:Antibody Formation; D000921:Antibody-Producing Cells / Q000276:immunology; D004405:Dysentery, Bacillary / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D018928:Immunity, Mucosal; D007115:Immunization Schedule; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D022281:Shigella Vaccines / Q000009:adverse effects / Q000276:immunology*; D012763:Shigella flexneri / Q000276:immunology; D055815:Young Adult
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D022281:Shigella Vaccines