PGG-Glucan (Alpha-Beta Technology, Inc.)

Twelve healthy horses were assigned to treatment or control groups. Treated horses received PGG-Glucan[ED-1] (1 mg/kg, IV) 24 hours prior to peripheral blood mononuclear cell (PBMC) isolation. PBMCs were isolated and incubated in the presence of lipopolysachharide (LPS). At 0, 6, 12, 24 and 48 hours messenger RNA (mRNA) was extracted. Reverse transcription polymerase chain reaction (PCR) was performed and cytokine mRNA expression for tumor necrosis factor alpha (TNFalpha), interleukin 1beta (IL-1beta), interleukin 10 (IL-10) and interferon gamma (IFN-gamma) determined using real time PCR. A significant effect of LPS stimulation over time was seen on TNFalpha, IL-1beta, IL-10 and IFN-gamma production. No significant difference was observed between the PGG-Glucan treatment group and control cells at any time point.

The recent events increasing the threat of bioterrorism have prompted a widespread search for defenses against this peril.

To evaluate the anthrax-protective effect of beta1,3-glucan immune modulators (PGG-glucan and WGP beta glucan) in an experimental animal model.

Beta1,3-glucan immune modulators were administered by subcutaneous injection to Balb/c mice 2 days prior to anthrax challenge. WGP beta glucan was administered by daily oral gavage for 7 days prior to challenge, or in drinking water for 10 days postchallenge with a lethal dose of Bacillus anthracis spores. Survival, survival time, and microbial bioburden relative to an infected, untreated control group were assessed.

A single injected dose of PGG-glucan or WGP beta glucan immune modulators given 2 days before challenge significantly: (a) increased the survival rate of infected mice (2.5-fold), (b) diminished the bacterial load in the lungs of infected mice (4-8-fold), and (c) increased the proportion of bacteria-free animals 10 days after challenge (2-fold). In mice prophylactically administered oral WGP beta glucan for 1 week prior to infection, survival increased from 50% to 100%; therapeutic administration of oral WGP beta glucan for 10 days postinfection increased survival from 30% up to 90% in treatment groups.

These results demonstrate the potential for beta1,3-glucan immune modulators to provide a significant degree of protection against anthrax, a potential biological warfare (BW) agent in a mouse model of anthrax infection. Further studies are needed to optimize protection, evaluate activity in combination with other treatment options, demonstrate activity in a validated primate model of infection, and determine if protection is effective against other potential BW agents.