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

BruceUa 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 <2% (wt/wt) contamination by protein and < 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 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.

Characterization of Biological Activities of Brucella melitensis Lipopolysaccharide

“…B. abortus LPS is reported to be a good candidate for a vaccine carrier because of the lower toxicity (13,14). The present study demonstrates that B. melitensis LPS exhibits a strong adjuvant action and that its toxicity was much less than that of E. coli LPS.…”

“…Further, the O antigen of Brucella LPS is a homopolymer of perosamine (4,6dideoxy-4-formamido-d-mannopyranosyl) (3,27,37). The biological activities such as cytokine production and lethality of S-LPS and rough types of LPS (R-LPS) from various Brucella strains are reported to be lower than those of enterobacterial LPS (4,14,25,29). The lower endotoxicity seems to be responsible for the unique lipid A structure of Brucella LPS.…”

Lipopolysaccharide from Brucella abortus behaves as a T-cell-independent type 1 carrier in murine antigen-specific antibody responses

“…In order to enhance the feasibility of using B. abortus as a potential carrier in vaccines, we extracted the LPS from B. abortus (LPS-BA) and conjugated it to the trinitrophenyl hapten (TNP-LPS-BA). The potential use of LPS from B. abornus in future vaccines is supported by recent toxicology studies performed in our laboratory (10). These studies demonstrated that LPS-BA is 300 to 10,000 times less potent than LPS-EC in a variety of assays, including the rabbit pyrogen test, mortality of D-galactosamine-sensitized mice, and IL-13 and tumor necrosis factor alpha induction from human monocytes.…”

“…The isotype switching in nude mice is probably attributable to low numbers of T cells found in the peripheral lymphoid organs of these mice (14). The differences in antibody induction between LPS-EC, LPS-BA, and B. abortus may be related to their relative abilities to stimulate IL-1 release from monocytes/macrophages (10), which could af- Ficoll or with 109 organisms of TNP-BA per mouse at 2-week intervals. Sera were collected 5 days after each injection.…”

Macrophage-elicited osteoclastogenesis in response toBrucella abortusinfection requires TLR2/MyD88-dependent TNF-α production

“…Although B. abortus possesses LPS, the generic endotoxin of Gram-negative organisms, it may derive its inflammatory capacity from lipoproteins. Differently from the LPS from the Enterobacteriaceae, Brucella LPS has thus far been found to be virtually devoid of proinflammatory activity [36]. Moreover, we have shown recently that the production of proinflammatory cytokines by different cell types of the innate immunity is induced by Brucella lipoproteins rather than LPS [27][28][29][30][31].…”