SparVax® rPA Anthrax Vaccine
RECOMBINANT PROTECTIVE ANTIGEN (rPA) ANTHRAX VACCINES
SPARVAX(®) – NOVEL SECOND GENERATION VACCINE TECHNOLOGY
Bacillus anthracis (Anthrax) Infection
Bacillus anthracis is a spore forming, gram positive bacterium that has potential to be used as a weapon of bioterror when delivered in an aerosolized form. Following germination of the spores, the bacteria replicates and produces three toxins. Anthrax Protective Antigen (PA) initiates the onset of the illness by attaching to cells in the infected person where it then facilitates entry of the two additional destructive toxins - Lethal Factor (LF) and Edema Factor (EF) into the cell.
Current Standard of Care
Antibiotics are the first line of defense against anthrax infection; however, early identification and treatment are critical for successful outcome. Even with aggressive antibiotic therapy, five of the eleven victims of the 2001 anthrax postal attacks died, underscoring the need for improved vaccines and anti-toxins for civilian protection. The current FDA licensed anthrax vaccine (BioThrax® Anthrax Vaccine Adsorbed) is approved for the prevention of anthrax infection, but requires five doses over a period of eighteen months to achieve protective immunity. AVA is a first generation anthrax vaccine made from cell free filtrates of whole bacterial cultures of Bacillus anthracis. This vaccine was first FDA licensed in 1970.
SparVax® Key Characteristics
SparVax® is a novel second generation recombinant protective (rPA) anthrax vaccine being developed to protect against inhalation anthrax, the most lethal form of anthrax infection in humans. It contains a single, highly purified protein, Protective Antigen, which is produced using a standard production strain of E.coli. SparVax® has been shown to stimulate protection against anthrax by eliciting a specific immune response to one of the primary proteins excreted by the Bacillus anthracis organism. In contrast, the currently available anthrax vaccine, which was initially developed nearly a half century ago and first licensed in 1970, is made from a culture filtrate derived from anthrax bacteria. Consequently, it contains a number of different proteins, some of which are believed to contribute to the adverse events that have been reported in the literature and which prompted agencies like the Institute of Medicine to recommend adoption of newer and safer modern vaccines.
Over the past 50 years, advances in modern vaccine technology have contributed to a vast improvement in public health. Production of new vaccines using modern recombinant protein technology has resulted in highly consistent, pure and well-defined vaccines that can be made using industrial biotechnology manufacturing capabilities on a large scale to meet flexible needs, such as surge capacity, at a reasonable cost.
Such technologies have been embraced by large pharmaceutical and vaccine manufacturers to produce vaccines with increased consistency and improved purity, such as pneumococcal and meningococcal vaccines and more recently, purified vaccines that use proteins produced by recombinant technology, such as the Hepatitis B vaccine.
These same modern manufacturing techniqueshave been adapted for the production of SparVax® in order that our Nation’s military personnel and civilians can benefit from these important advances in modern vaccine technology to the same degree that the civilian population benefits from improvements in commercial vaccine products.
The use of modern vaccine production technologies for the manufacture of SparVax® has resulted in several advantages:
· Provides greater flexibility of manufacturing options and the ability to readily scale up and/or tech transfer the process to meet domestic or international surge capacity demand.
· Results in a high yielding manufacturing process, which enables greater efficiency in the costs of production and therefore a product which is more economical to manufacture.
· Enables the development of a product with improved purity.
One Phase I and two Phase II clinical trials involving more than 700 healthy human subjects have been completed to date. No vaccine-related serious adverse events were reported in these studies. In preclinical animal studies, SparVax® has demonstrated the capability to protect rabbits and non-human primates against a lethal aerosol spore challenge of the anthrax Ames strain.
Government funding commitments of up to $213 million have been awarded to date for the SparVax® rPA anthrax program, which includes additional funding of up to $78.4 million under a contract modification for SparVax® announced in February 2010.
SparVax® had been developed initially by the Defence Science and Technology Laboratory (Dstl) in the United Kingdom. PharmAthene has obtained an exclusive license to the product from Dstl.
Third Generation rPA Vaccine Program
The objective of PharmAthene’s third generation program is to develop an rPA anthrax vaccine which can maintain stability for three years at 35ºC and induce protective immunity in two or fewer doses. The primary objective of the program is to develop an rPA-based anthrax vaccine that can be stored, transported and used without the need for a conventional cold chain – an important advantage for civilian biodefense deployment within the Strategic National Stockpile.