An idiotype vaccine against gram-negative bacterial sepsis

Abstract

This chapter reviews research on an idiotype (Id) vaccine designed to help prevent gram-negative bacterial sepsis and shock. Gram-negative sepsis and septic shock are caused by the body's response to the presence of bacteria—particularly, the presence of lipopolysaccharide (LPS) or endotoxin, the main surface glycolipid in all gram-negative bacteria. One promising technique for treatment of this disease involves the use of antibodies specific for LPS. The rationale for this treatment is that clearance of endotoxin levels in the bloodstream would improve the outcome of patients with this disease. The series of studies discussed in the chapter attempts to actively manipulate the immune response against LPS to prevent bacterial sepsis and shock, and for this purpose an idiotype (Id) vaccine was developed. A murine monoclonal antibody, termed IC9, that was specific for the lipid A portion of LPS was obtained that can passively protect against endotoxin shock and bacteremia in mouse models. An interspecies cross-reactive Id (IdX) associated with the antilipid A antibody response was defined using anti-Ids. Then, the ability of the monoclonal antibodies to act as a vaccine against gram-negative bacterial infection and shock was tested to see if the anti-IC9 idiotopes were also able to induce antilipid A responses in different species.