| Autor: |
Passwell, Justen H., Harlev, Efrat, Ashkenazi, Shai, Chu, Chiayung, Miron, Dan, Ramon, Reut, Farzan, Naheed, Shiloach, Joseph, Bryla, Dolores A., Majadly, Fathy, Roberson, Robin, Robbins, John B., Schneerson, Rachel |
| Zdroj: |
Infection and Immunity; March 2001, Vol. 69 Issue: 3 p1351-1357, 7p |
| Abstrakt: |
ABSTRACTData suggest that the O-specific polysaccharide (O-SP) domain of the lipopolysaccharide (LPS) of Shigellaspecies is both an essential virulence factor and a protective antigen and that a critical level of serum immunoglobulin G (IgG) to this antigen will confer immunity to shigellosis. Because covalent attachment of polysaccharides to proteins increases their immunogenicity, especially in infants and in young children, the O-SP of Shigellaspecies were bound to medically useful proteins, and the safety and immunogenicity of the resultant conjugates were confirmed in adults and 4- to 7-year-old children. Succinylation of the carrier protein improved the immunogenicity of Shigellaconjugates in mice and increased their yield. Based on these results, a clinical trial of O-SP conjugates of Shigella sonneiand Shigella flexneri2a bound to succinylated mutant Pseudomonas aeruginosaexotoxin A (rEPAsucc) or native or succinylated Corynebacterium diphtheriaetoxin mutant (CRM9 or CRM9succ) was conducted in healthy adults. The conjugates were safe and immunogenic. S. sonnei-CRM9,S. sonnei-CRM9succ, and S. sonnei-rEPAsuccelicited significant rises of geometric mean (GM) IgG anti-LPS within 1 week of injection (P< 0.001). At 26 weeks, the GM anti-LPS levels elicited by these three conjugates were similar and higher than their prevaccination levels (P< 0.0001). GM IgG anti-LPS levels elicited by S. flexneri2a-rEPAsuccwere significantly higher than those elicited by S. flexneri2a-rCRM9succat all intervals after injection. At 26 weeks, the levels of IgG anti-LPS in vaccinees were higher than their prevaccination levels (P< 0.0001). The serum antibody responses were specific, as there was no significant rise of anti-LPS to the heterologous O-SP in any vaccinee. Both conjugates elicited statistically significant rises of serum antibodies to the injected carrier protein. At 6 months, these five Shigellaconjugates elicited higher fold rises than similar conjugates (D. N. Taylor et al., Infect. Immun. 61:3678–3687, 1993). Based on these data, we chose S. sonnei-CRM9 and S. flexneri2a-rEPAsuccfor evaluation in children. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
