title: Lipopolysaccharide (LPS) from Brucella abortus is less toxic than that from Escherichia coli, suggesting the possible use of B. abortus or LPS from B. abortus as a carrier in vaccines.
abstract: Brucella abortus may be useful as a component of vaccines. This is because it possesses several unique properties as a carrier that enable it to stimulate human B cells even in the relative absence of T cells. Human immunodeficiency virus type 1 proteins conjugated to B. abortus could induce neutralizing antibodies against human immunodeficiency virus type 1. Recently we showed that the characteristics of lipopolysaccharide (LPS) derived from B. abortus are similar to those of the whole bacterium in that the LPS acts as a T-independent type 1 carrier in mice. In this study we wanted to determine whether LPS derived from B. abortus is associated with the adverse effects seen with other bacterial endotoxins. LPS purified from B. abortus by butanol extraction was shown to have less than 2% (wt/wt) contamination by protein and less than 1% (wt/wt) contamination by nucleic acids and to contain 1% (wt/wt) ketodeoxyoctanic acid. Compared with LPS derived from Escherichia coli, B. abortus LPS was 10,000-fold less potent in eliciting fever in rabbits, 268-fold less potent in killing D-galactosamine-sensitized mice, and 1,400-fold and 400-fold less potent in inducing interleukin-1 beta and tumor necrosis factor alpha production, respectively. These results suggest that B. abortus LPS is much less likely than the LPS from E. coli to evoke endotoxic shock; therefore, it may be feasible to incorporate B. abortus as a component of vaccines.
authors.affiliation: Laboratory of Cell Biology, U.S. Food and Drug Administration, Bethesda, Maryland 20892.
authors.forename: J
authors.initials: J
authors.lastname: Goldstein
authors.forename: T
authors.initials: T
authors.lastname: Hoffman
authors.forename: C
authors.initials: C
authors.lastname: Frasch
authors.forename: E F
authors.initials: EF
authors.lastname: Lizzio
authors.forename: P R
authors.initials: PR
authors.lastname: Beining
authors.forename: D
authors.initials: D
authors.lastname: Hochstein
authors.forename: Y L
authors.initials: YL
authors.lastname: Lee
authors.forename: R D
authors.initials: RD
authors.lastname: Angus
authors.forename: B
authors.initials: B
authors.lastname: Golding
mesh_terms: D000818:Animals; D002003:Brucella abortus; D004306:Dose-Response Relationship, Immunologic; D004591:Electrophoresis, Polyacrylamide Gel; D004731:Endotoxins / Q000032:analysis; D004926:Escherichia coli; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D007928:Lethal Dose 50; D008070:Lipopolysaccharides / Q000032:analysis / Q000633:toxicity*; D051379:Mice; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D004731:Endotoxins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha