Soligenix, Inc. today announced promising preliminary results from a preclinical study with its ricin toxin vaccine RiVax, in a non-human primate (NHP) lethal aerosol exposure model.
The study demonstrated that NHPs vaccinated with RiVax were completely protected against a lethal aerosol of ricin toxin with a highly significant survival benefit (p<0.002). RiVax, manufactured with the company’s thermostabilization platform technology ThermoVax, was used to vaccinate NHPs to assess efficacy against lung exposure to ricin toxin in an animal model that is anticipated to respond to vaccination similarly to humans.
ThermoVax provides for stabilized, lyophilized (freeze-dried) subunit vaccines that are resistant to exposure to heat, avoiding refrigeration during storage and distribution.
In this pilot study, the ability of the stabilized RiVax vaccine to protect against an aerosolized form of ricin toxin was evaluated. Animals were exposed to an aerosol of ricin toxin 3-5 times the amount that is known to result in death of untreated animals. In the case of vaccinated NHPs, the vaccine regimen was safe and well-tolerated, with all of the animals developing antibodies in their sera that neutralized the activity of ricin toxin.
More importantly, all of the NHPs in the RiVax-vaccinated treatment group survived when exposed to the respiratory aerosol of ricin toxin, with no apparent signs of gross lung damage. Conversely, all NHPs in the unvaccinated treatment group died within approximately 36 hours of exposure to aerosolized ricin while developing severe lung damage, including hemorrhaging.
“We are extremely pleased with the positive preliminary efficacy results with RiVax in NHPs. This particular study is a critical step along the path of establishing efficacy under the FDA ‘animal rule’ which dictates that efficacy in animals must be ascertained in cases where a drug or vaccine cannot be ethically tested for efficacy in humans,” stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. “It is clear that vaccination with heat stable RiVax resulted in robust protection against lung exposure, the most dangerous and likely way that ricin toxin could be used. We anticipate further development of RiVax in order to conduct human safety and immunogenicity trials along with advanced manufacturing.”
The vaccination and exposure studies were conducted at the Tulane National Primate Research Center (TNPRC) under the direction of Dr. Chad Roy, Director of Infectious Disease Aerobiology. These studies were performed under sponsorship of a National Institute of Allergy and Infectious Disease (NIAID) cooperative grant to Soligenix with TNRPC and other collaborators.
Ricin is a plant toxin thought to be a bioterror threat because of its stability and high potency as well as the large worldwide reservoir created as a by-product of castor oil production. Ricin comes in many forms like powder, mist, pill, or pellet. Ricin can also be dissolved in water and other liquids. As a poison, ricin is so potent that the US Centers for Disease Control (CDC) estimates the lethal dose in humans is about the size of a grain of salt.
Exposure to ricin results in local tissue necrosis and general organ failure leading to death within several days of exposure, and is especially toxic when inhaled. Ricin is a ribosome inactivating protein (RIP) and a potent member of the AB family of toxins. The enzymatic ricin toxin A subunit (RTA) is an RNA-N-glycosidase which cleaves a specific adenine residue with eukaryotic 28S ribosomal RNA, leading to protein synthesis arrest and cell death.
There are currently no effective means to prevent the effects of ricin poisoning. The successful development of an effective vaccine against ricin toxin may act as a deterrent against the actual use of ricin as a biological weapon and could be used in rapid deployment scenarios in the event of a biological attack.
Source: Soligenix press release, adapted. RiVax and ThermoVax are trademark protected terms of Soligenix.