Current State And Future Of Polysaccharide-Based V
In 1980, covalent binding Haemophilus influenzae type b (Hib) capsular polysaccharide (CPS) to medically-acceptable proteins to form a conjugate was reported. Hib conjugates had both enhanced immunogenicity and, in contrast to the CPS alone, induced a booster in infants. Addition of Hib conjugates into routine immunization of infants has virtually eliminated systemic infections, especially meningitis, caused by this pathogen at all ages (herd immunity). The host factor responsible is conjugate-induced serum IgG anti-Hib CPS, exuding onto the respiratory epithelium and inactivating the inoculum. Because it is an inhabitant of humans only, Hib may be eradicated by universal immunization as was with smallpox. The dosage of and multivalent antigen formulations with Hib conjugates are under study.
Conjugate technology has been extended successfully to pneumococci, meningococcus and Salmonella typhi. In the latter, a Vi conjugate induced ~92% efficacy against typhoid in 2-5 year-olds in Vietnam. Recently, types 5 and 8 CPS conjugates of Staphylococcus aureus were shown to be safe, immunogenic, and effective in preventing bacteremia in patients on hemodialysis. CPS conjugates of Vibrio cholerae O139 have undergone successful pre-clinical study. It is anticipated that CPS conjugate vaccines will be developed for other opportuistic infections including S. aureus coagulase negative, enteroccocci, Klebsiella pneumoniae, and Escherichia coli.
Conjugates of the O-specific polysaccharide domain of LPS from Gram-negative enteric pathogens have been shown to be safe, immunognic, and for Shigella sonnei in Israel army recruits, have been effective. Conjugate vaccines for Salmonella paratyphi A, V. cholerae O1 and E. coli O157 have been shown to be safe and immunogenic. Improvement in the immunogenicity of Shigella vaccines has been achieved by development of conjugates composed of synthetic polysaccharides of Shigella dysenteriae type 1. This approach is being extended to other polysaccharide-protein conjugates., http://www.100md.com
Conjugate technology has been extended successfully to pneumococci, meningococcus and Salmonella typhi. In the latter, a Vi conjugate induced ~92% efficacy against typhoid in 2-5 year-olds in Vietnam. Recently, types 5 and 8 CPS conjugates of Staphylococcus aureus were shown to be safe, immunogenic, and effective in preventing bacteremia in patients on hemodialysis. CPS conjugates of Vibrio cholerae O139 have undergone successful pre-clinical study. It is anticipated that CPS conjugate vaccines will be developed for other opportuistic infections including S. aureus coagulase negative, enteroccocci, Klebsiella pneumoniae, and Escherichia coli.
Conjugates of the O-specific polysaccharide domain of LPS from Gram-negative enteric pathogens have been shown to be safe, immunognic, and for Shigella sonnei in Israel army recruits, have been effective. Conjugate vaccines for Salmonella paratyphi A, V. cholerae O1 and E. coli O157 have been shown to be safe and immunogenic. Improvement in the immunogenicity of Shigella vaccines has been achieved by development of conjugates composed of synthetic polysaccharides of Shigella dysenteriae type 1. This approach is being extended to other polysaccharide-protein conjugates., http://www.100md.com