Active immunization with a detoxified Escherichia coli J5 lipopolysaccharide group B meningococcal outer membrane protein complex vaccine protects animals from experimental sepsis

The passive infusion of antibodies elicited in rabbits with a detoxified J5 lipopolysaccharide (LPS)/group B meningococcal outer membrane protein comp lex vaccine protected neutropenic rats from heterologous lethal gram-negati ve bacterial infection. In this study, active immunization was studied in n eutropenic rats infected with Pseudomonas aeruginosa, in the presence or ab sence of ceftazidime therapy, and with Klebsiella pneumoniae. This vaccine elicited a >200-fold increase in anti-J5 LPS antibody, which remained eleva ted throughout the duration of cyclophosphamide-induced neutropenia and for less than or equal to3 months. There was improved survival among immunized versus control animals: 48% (13/28) versus 7% (2/29) in Pseudomonas-challe nged rats; 61% (11/18) versus 0% (0/10) in Pseudomonas- and ceftazdime-trea ted rats; and 64% (9/14) versus 13% (2/15) in Klebsiella-challenged rats (P < .01 for each comparison). Immunized animals had lower levels of bacteria in organs and lower levels of circulating endotoxin at the onset of fever. In conclusion, active immunization with an anti-endotoxin vaccine improved survival after infection with <greater than or equal to>2 heterologous, cl inically relevant bacterial species in immunocompromised animals. Active im munization with this vaccine merits further investigation.