VACCINES PROTECTIVE AGAINST GRAM-NEGATIVE BACTEREMIA AND ENDOTOXIC SHOCK AND RELATED DIAGNOSIC ASSAYS

摘要

The present invention is directed to the development of monoclonal anti-idiotypic antibodies (anti-ids) which mimic a common antigenic determinant on the lipid A portion of the Lipopolysaccharite (LPS) of gram-negative bacteria. More particularly, the invention comprises the development of hybridomas A4, H9, and H12 which produce monoclonal anti-Ids that mimic a common antigenic determinant on the lipid A portion of the LPS molecule found on a number of different bacterial strains. The development of the hybridomas was carried out by induction with a monoclonal antibody, 1C9, which recognizes a conserved epitope, that is a target for a bactericidal antibody, or involved in immune clearance mechanisms, and is common to all Enterobacteriaceae gram-negative bacteria. The anti-Ids contain a protein image of the lipid antigen and are thus capable of stimulating anti-LPS activity. Therefore, the anti-Ids of the present invention may be used as immunogens in vaccine formulations designed to protect against gram-negative bacteremia and septic shock. In one embodiment of a vaccine formulation in accordance with the present invention, the peptides could be generated based on the identity of the sequences of the idiotopes of anti-Ids. Alternatively, the DNA encoding the idiotopes which mimic the lipid A antigenic determinant may be used by applying molecular cloning techniques to direct production of the peptides. Additionally, the DNA itself may be incorporated into various vaccine-related vectors for vaccine applications.