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 complex vaccine protected neutropenic rats from heterologous lethal gram-negative bacterial infection. In this study, active immunization was studied in neutropenic rats infected with Pseudomonas aeruginosa, in the presence or absence of ceftazidime therapy, and with Klebsiella pneumoniae. This vaccine elicited a > 200-fold increase in anti-J5 LPS antibody, which remained elevated throughout the duration of cyclophosphamide-induced neutropenia and for < or = 3 months. There was improved survival among immunized versus control animals: 48% (13/28) versus 7% (2/29) in Pseudomonas-challenged rats; 61% (11/18) versus 0% (0/10) in Pseudomonas- and ceftazidime-treated rats; and 64% (9/14) versus 13% (2/15) in Klebsiella-challenged rats (P < 0.01 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 > or = 2 heterologous, clinically relevant bacterial species in immunocompromised animals. Active immunization with this vaccine merits further investigation.
Division of Infectious Diseases, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. across@umm.edu
A S
AS
Cross
S M
SM
Opal
H S
HS
Warren
J E
JE
Palardy
K
K
Glaser
N A
NA
Parejo
A K
AK
Bhattacharjee
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D002442:Ceftazidime / Q000627:therapeutic use; D002511:Cephalosporins / Q000627:therapeutic use; D003520:Cyclophosphamide; D004195:Disease Models, Animal; D018572:Disease-Free Survival; D004731:Endotoxins / Q000097:blood; D004926:Escherichia coli / Q000276:immunology*; D022361:Escherichia coli Vaccines / Q000008:administration & dosage*; D005260:Female; D007711:Klebsiella pneumoniae; D008070:Lipopolysaccharides / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology*; D009503:Neutropenia / Q000139:chemically induced; D011550:Pseudomonas aeruginosa; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D018074:Vaccines, Conjugate
D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002511:Cephalosporins; D004731:Endotoxins; D022361:Escherichia coli Vaccines; D008070:Lipopolysaccharides; D018074:Vaccines, Conjugate; D003520:Cyclophosphamide; D002442:Ceftazidime