BROAD-SPECTRUM LPS BASED VACCINES OF UNENCAPSULATED STRAINS OF HAEMOPHILUS INFLUENZAE AND OTHER PATHOGENIC SPECIES OF GRAM-NEGATIVE BACTERIA

摘要

Vaccines prepared using purified LPS of unencapsulated (non-typeable) Haemophilus influenzae detoxified by a strategy which leaves structurally intact the native Lipid A moiety, presereing broadly cross-reactive epitopes expressed by an antigenic supramolecular structure composed of at least 50 LPS monomers. The detoxification strategy preferentially involves the formation of the equimolar complex between by the Lipid A moiety of LPS and the cyclic synthetic peptide with the sequence NH2-Lys-Thr-Lys-Cys-Lys-Phe-Leu-Leu-Leu-Cys-COOH, CysA-Cys10 disulfide. The same strategy of detoxification resulting in the preservation of the supramolecular, micelle-like, structure of native NTHi LPS is extended to LPS antigens purified from other pathogenic species of bacteria, in order to generate the homologous endotoxoid vaccines.