title: Safety and immunogenicity of investigational Shigella conjugate vaccines in Israeli volunteers.
abstract: The safety and immunogenicity of investigational conjugates, composed of the O-specific polysaccharides of Shigella sonnei and Shigella flexneri type 2a covalently bound to Pseudomonas aeruginosa recombinant exoprotein A (rEPA), were evaluated in 192 Israeli soldiers. None had significant local reactions or fever. Fourteen days after injection, 90% of S. sonnei-rEPA recipients and 73 to 77% of S. flexneri-rEPA recipients had a fourfold or greater increase in serum immunoglobulin G (IgG) and IgA anti-lipopolysaccharide (anti-LPS) levels; at 2 years, these remained higher than at prevaccination (P < 0.01). There was a fourfold or greater increase in IgM anti-LPS in 20% of vaccinees at 2 weeks, but levels returned to prevaccination values at 6 to 12 months. IgG was the highest and most sustained class of LPS antibodies. Reinjection at day 42 did not boost antibody levels. Eighteen of 23 (78%) who received S. sonnei-rEPA and 13 of 19 (68%) who received S. flexneri-rEPA. had significant IgA-secreting cell responses. Significant IgG antibody-secreting cell responses were detected in 19 of 23 (83%) and 11 of 19 (58%) volunteers following vaccination with S. sonnei-rEPA and S. flexneri 2a-rEPA, respectively. On the basis of these data, further evaluation of the Shigella conjugates for protective efficacy in field trials in Israel was started.
authors.affiliation: Medical Corps, Israel Defence Force and Sackler School of Medicine, Tel Aviv University.
authors.forename: D
authors.initials: D
authors.lastname: Cohen
authors.forename: S
authors.initials: S
authors.lastname: Ashkenazi
authors.forename: M
authors.initials: M
authors.lastname: Green
authors.forename: Y
authors.initials: Y
authors.lastname: Lerman
authors.forename: R
authors.initials: R
authors.lastname: Slepon
authors.forename: G
authors.initials: G
authors.lastname: Robin
authors.forename: N
authors.initials: N
authors.lastname: Orr
authors.forename: D N
authors.initials: DN
authors.lastname: Taylor
authors.forename: J C
authors.initials: JC
authors.lastname: Sadoff
authors.forename: C
authors.initials: C
authors.lastname: Chu
authors.forename: J
authors.initials: J
authors.lastname: Shiloach
authors.forename: R
authors.initials: R
authors.lastname: Schneerson
authors.forename: J B
authors.initials: JB
authors.lastname: Robbins
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D012760:Shigella / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D018074:Vaccines, Conjugate