Fear of botulism as a bioterrorist weapon is to be reduced by British vaccine technology

Feb 28 2005

Fear of botulism as a bioterrorist weapon is to be reduced, as the US government announces its support for a new British vaccine technology, which promises for the first time to provide an effective defence against botulism – the most deadly naturally occurring substance.

The US National Institute of Allergy and Infectious Diseases (NIAID), has awarded a $3.5m grant to Cambridge Biostability Ltd, developers of a new stable vaccine technology, to work alongside the DVC LLC in the creation of a new vaccine against botulism.

The technology developed by Cambridge Biostability will for the first time enable the development of a stable vaccine for botulism. Rendering it no greater risk to public health than tetanus and effectively neutralising the danger of botulism as a potential weapon.

Lord Sainsbury, Department of Trade and Industry Science Minister, said: “The US biosecurity market is estimated to be over $14 billion. Cambridge Biostability’s success demonstrates the leading role that British bioscience companies are taking in Europe in penetrating this market and is an excellent example of how British Universities are turning expert research into practical applications.”

Botulinum toxin is a poison; it is not infectious but can be inhaled if released deliberately as a powder into the atmosphere. It affects the body within hours, resulting in death or a paralysis, which can last for months, during which time the casualty is unable to breathe without a respirator. Tetanus is also neurotoxin, which once deadly is now successfully controlled by vaccination.

Until now a single vaccine has not been possible as Bruce Roser, Chief Scientific Advisor for Cambridge Biostability explains: “The problem is that Botulism is caused by seven slightly different poisons produced by six different bugs. In the event of an attack a person would need to be given multiple vaccine injections to cover all the bugs and three shots are required of each vaccine.

“The vaccine is created by turning the poison into a toxoid – a weaker non-toxic version that still triggers an immune response in the body. Each type of toxoid needs to be kept separately, buffered with the right amount of acidity to keep it in solution; if this is not exact the toxoid is destroyed.

“With our stable liquid technology you can encapsulate each toxoid in its own microsphere. The microspheres can be mixed and kept at room temperature without harming the vaccine. This means that for the first time it is possible to create a single multivalent vaccine which can be stored safely without refrigeration.”

The new technology is based on a natural phenomenon. Some plants and creatures can remain in a desiccated state for hundreds of years by reducing the water content of their bodily fluids. Water within the cells is replaced with a sugar solution that thickens when water is excluded to a point of solidifying as a glass and the organism dries out. When rehydrated they ‘return to life’.

This process is being applied for the first time to vaccines. Sugar hardens to form a non-crystalline glass. So the vaccine is first spray-dried using the sugar syrup to form microscopic glass spheres. The dry vaccine is then suspended in an approved inert liquid, which can be injected into muscle where bodily fluids reactivate the vaccine.

The new botulism vaccine offers for the first time a viable means of providing an effective deterrent against bioterrorist attack. As it is very similar to the tetanus toxoid mass vaccination of the entire population would be feasible. Alternatively first responders to an outbreak, such as paramedics or firefighters, can be immunised and the outbreak contained.

Cambridge Biostability will be working in collaboration with DVC LLC, which is organising the production of seven different toxoids, altering the gene in each to make the poison antigenic but not toxic. As each vaccine emerges the technology to stabilise it will also be applied.

Principal Investigator Dr Ian Henderson, Ph.D DVC LLC says that the new technology is a major breakthrough: “Each serotype of botulinum neurotoxin requires its own vaccine to provide protection. This means that to cover all possibilities of combating botulism, both natural and man-made, a single vaccine formulation should contain all seven vaccine antigens, each optimally formulated to maximize protection and stability. The new technology developed by Cambridge Biostability Ltd. has the potential to make such a goal a reality, combining potent vaccine formulations with long term high temperature stability characteristics, with the prospect of eliminating the cold chain.”

Dr Roser sees the partnership with DVC LLC as the first important phase in a long-term programme culminating in the production, development, scale-up and manufacture of a maximally stable and potent botulinum vaccine. Cambridge Biostability also intends to make its technology available for the development of stable liquid versions of the other vaccines in the Biodefense Initiative. The stable liquid format is ideal for stockpiling vaccines in an instantly injectable form without the need for refrigeration.