Cambridge Biostability Ltd (CBL) has successfully passed the first milestone in its collaboration with DynPort Vaccine Company LLC (DVC), a Computer Sciences Corporation company, to develop a stable vaccine against the seven different neurotoxins that cause botulism. The botulinum neurotoxin is generally recognized as the deadliest known naturally occurring substance.
Non-clinical studies have shown that two vaccine candidates designed to provide protection against two of the seven neurotoxins, stabilized by CBL and then combined and stored at a range of temperatures up to 55°C, were as effective in providing protection as fresh vaccine preparations. Under the same test conditions unstabilised vaccine stored at 55°C did not provide protection. Therefore, CBL has demonstrated the ability to produce a stable liquid, multi-component recombinant vaccine which would be ideal for establishing biodefense stockpiles without the need for refrigeration.
CBL is a major collaborator in a $5.4 million grant awarded to DVC by the National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health (Grant Number 1 UC1 AI062531-01). The work aims to embed the botulinum vaccine antigens within stable glass microspheres suspended in an anhydrous fluorocarbon liquid, enabling the development of a single ready-to-inject multivalent vaccine against botulism.
The stockpiling of any vaccine presents a series of chemical and logistical challenges to ensure the effectiveness and potency of stored supplies. However, botulism brings an additional problem. "Botulism can be caused by seven different neurotoxins that each require its own vaccine," explains Dr. Bruce Roser, Chief Scientific Advisor for Cambridge Biostability. "Our aim is to provide a single, stable vaccine preparation of all of the antigens that would provide comprehensive protection to those that receive such a vaccine. This would be a considerable feat given that each antigen has unique properties."
Dr Ian Henderson, Senior Scientist at DVC and Principal Investigator on the grant, explains that the initial results are very promising. "These milestone results have exceeded our expectations and show that this new approach to vaccine development has real potential for a range of biodefense vaccines currently under consideration," he said.
The key to this success is a technology, which is widely used outside the vaccine industry spray drying. Stabilising chemicals are combined with vaccines and the mixture is dried in a jet of hot, dry gas to form glass microspheres. Once the labile vaccine is embedded in the microsphere, all chemical reactions stop and the vaccine is stable. The microspheres are then suspended in an inert, anhydrous liquid to give a smooth suspension. This liquid is injected into the patient where the microspheres dissolve in the body's fluids, thereby releasing the vaccine. By simply mixing different microspheres in the inert liquid many vaccines can be combined in a single dose.
"This means it is possible to create a single multivalent vaccine that can be stored safely without refrigeration," says Dr. Roser. "This paves the way for more dispersed stockpiles, making the vaccines more accessible for distribution."
Dr Henderson sees the collaboration with CBL as the first important phase in a long-term programme culminating in the production, development, scale-up and manufacture of a stable multivalent botulinum vaccine. CBL's technology is also applicable for the development of stable liquid versions of the other vaccines in the Biodefence Initiative.
CBL is part of a research team led by DVC, a technology integrator managing the complete biologics development life cycle. The vaccine antigens and related data used in the achievement of the current milestone were provided by the Department of Defense through the Joint Vaccine Acquisition Program (JVAP). Initial development of these products was performed by The United States Army Medical Research Institute of Infectious Diseases (USAMRIID).