title: Phase 1 and phase 2 studies of Salmonella enterica serovar paratyphi A O-specific polysaccharide-tetanus toxoid conjugates in adults, teenagers, and 2- to 4-year-old children in Vietnam.
abstract: Salmonella enterica serovar Paratyphi A O-specific polysaccharide (O-SP) was activated with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) and bound to tetanus toxoid (TT) with adipic acid dihydrazide as a linker (SPA-TT(1)) or directly (SPA-TT(2)). In mice, these two conjugates elicited high levels of immunoglobulin G (IgG) anti-lipopolysaccharide (LPS) in serum with bactericidal activity (E. Konadu, J. Shiloach, D. A. Bryla, J. B. Robbins, and S. C. Szu, Infect. Immun. 64:2709-2715, 1996). The safety and immunogenicity of the two conjugates were then evaluated sequentially in Vietnamese adults, teenagers, and 2- to 4-year-old children. None of the vaccinees experienced significant side effects, and all had preexisting LPS antibodies. At 4 weeks after injection, there were significant increases of the geometric mean IgG and IgM anti-LPS levels in the adults and teenagers: both conjugates elicited a greater than fourfold rise in the IgG anti-LPS level in serum in >/=80% of the volunteers. SPA-TT(2) elicited slightly higher, though not statistically significantly, levels of IgG anti-LPS than did SPA-TT(1) in these age groups. Accordingly, only SPA-TT(2) was evaluated in the 2- to 4-year-old children. On a random basis, one or two injections were administered 6 weeks apart to the children. No significant side effects were observed, and the levels of preexisting anti-LPS in serum were similar in children of all ages. A significant rise in the IgG anti-LPS titer was elicited by the first injection (P = 0.0001); a second injection did not elicit a booster response. Representative sera from all groups had bactericidal activity that could be adsorbed by S. enterica serovar Paratyphi A LPS.
authors.affiliation: National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-2720, USA.
authors.forename: E Y
authors.initials: EY
authors.lastname: Konadu
authors.forename: F Y
authors.initials: FY
authors.lastname: Lin
authors.forename: V A
authors.initials: VA
authors.lastname: Hó
authors.forename: N T
authors.initials: NT
authors.lastname: Thuy
authors.forename: P
authors.initials: P
authors.lastname: Van Bay
authors.forename: T C
authors.initials: TC
authors.lastname: Thanh
authors.forename: H B
authors.initials: HB
authors.lastname: Khiem
authors.forename: D D
authors.initials: DD
authors.lastname: Trach
authors.forename: A B
authors.initials: AB
authors.lastname: Karpas
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: D A
authors.initials: DA
authors.lastname: Bryla
authors.forename: J B
authors.initials: JB
authors.lastname: Robbins
authors.forename: S C
authors.initials: SC
authors.lastname: Szu
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D002675:Child, Preschool; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology; D019081:O Antigens / Q000276:immunology*; D012482:Salmonella paratyphi A / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D019081:O Antigens; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate