Phase 1 and Phase 2 Studies ofSalmonella entericaSerovar Paratyphi A O-Specific Polysaccharide-Tetanus Toxoid Conjugates in Adults, Teenagers, and 2- to 4-Year-Old Children in Vietnam
| Autor: | Tran Cong Thanh, Arthur B. Karpas, Dang Duc Trach, Jianping Li, Edward Konadu, Nguyen Thi Thanh Thuy, Vo Anh Ho, Shousun C. Szu, Feng-Ying C. Lin, Dolores A. Bryla, John B. Robbins, Ha Ba Khiem, Phan Van Be Bay |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
Lipopolysaccharides Serotype Adolescent Immunology Microbiology Immunoglobulin G Tetanus Toxoid medicine Humans Vaccines Conjugate biology Tetanus business.industry Immunogenicity Toxoid Salmonella paratyphi A O Antigens medicine.disease Antibodies Bacterial Titer Infectious Diseases Immunoglobulin M Child Preschool Microbial Immunity and Vaccines biology.protein Parasitology Antibody business |
| Zdroj: | Infection and Immunity. 68:1529-1534 |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | Salmonella entericaserovar 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-TT1) or directly (SPA-TT2). 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-TT2elicited slightly higher, though not statistically significantly, levels of IgG anti-LPS than did SPA-TT1in these age groups. Accordingly, only SPA-TT2was 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 byS. entericaserovar Paratyphi A LPS. |
| Databáze: | OpenAIRE |
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