Posted on 11/01/2001 4:10:55 PM PST by aculeus
Bethesda, MD. - A new, less-toxic and longer-lasting vaccine against anthrax is ready for clinical trials, say researchers from the Center for Biotechnology at Jawaharlal Nehru University in New Delhi, India. The team, led by Rakesh Bhatnagar, created harmless mutant forms of the three key proteins that together make anthrax fatal. The researchers bioengineered the anthrax proteins so that they could be expressed in safer hosts to produce immunogens for the new vaccine. In abstracts submitted for presentation to the Annual Meeting of the American Society for Cell Biology to take place in December, Bhatnagar reports scaling up the original experimental bioreactor to a near industrial-sized unit that can manufacture enough vaccine for upcoming human trials.
Anthrax toxin complex, which is responsible for the most dangerous effects of the disease, consists of three proteins: protective antigen, lethal factor and edema factor. Individually, the proteins are non-toxic. However, combining the protective antigen with lethal factor creates lethal toxin. Mixing protective antigen plus edema factor creates an edema toxin, which causes swelling and redness of the skin.
Protective antigen is the central component of anthrax toxin. This antigen binds to cell-surface receptors and mediates the entry of the other two components into the cell cytosol. It is also the main immunogen of the vaccine against anthrax. Including trace amounts of lethal factor and edema factor in the vaccine improves its efficacy.
Bhatnagar and his colleagues introduced mutations into all three proteins of the anthrax toxin complex, rendering them non-toxic. They then studied these mutated proteins intensively to understand how they act at the cellular level. They concluded that the mutant proteins were excellent candidates for an anthrax vaccine. The mutations made the proteins non-toxic but did not affect their distinctive molecular shapes, which are required to generate protective antibodies.
The anthrax vaccine currently used for immunization causes many side effects and requires booster doses, according to Bhatnagar. To create an improved vaccine, his lab introduced the genes for the mutated proteins into relatively safe host organisms. Expressed in quantity by their bioengineered hosts, the mutant proteins were then purified to homogeneity to ensure that reactivity and side effects of the vaccine were minimized.
Once they were confident that they could overexpress the protective antigens on a laboratory scale, Bhatnagar's team took the production to industrial scale with only a 5-liter capacity fermenter that can now produce approximately 5 grams of protective antigen per liter. One gram of this product can supply millions of vaccine shots. This antigen will soon undergo clinical trials, says Bhatnagar. Mass immunization with a safe and effective anthrax vaccine could thwart the attempts of terrorists to use anthrax as a biological warfare agent.
Dr. Bhatnagar will present three abstracts on his anthrax vaccine work at the Annual Meeting of the American Society for Cell Biology, on Tuesday, December 11 at the Washington Convention Center in Washington, D.C. He will also be available to the press at the ASCB's annual Press Conference, on Monday, December10 at 3:30 PM in the Convention Center.
Good question.
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