Indian anthrax vaccine gains international recognition

By R. Prasad

CHENNAI, NOV. 13. Indian scientists have shot into limelight in the wake of the world campaign against terrorism by developing a safer anthrax vaccine for humans. Recognition has come quickly even from the developed countries. The vaccine has superior attributes like lesser toxicity and longer protection, compared to the vaccine now being produced in the U.S. But more importantly, the bioengineered vaccine has no side effects.

The vaccine developed by Dr. Rajesh Bhatnagar, Chairman of the Centre for Biotechnology, JNU, Delhi and Dr. Yogendra Singh of the Centre for Biochemical Technology, Delhi, have mutant forms of the three proteins that make anthrax fatal. The mutant forms of the three proteins - protective antigen, oedema factor, and lethal factor - were bioengineered to make them harmless when used in a vaccine. ``The anthrax presently available is not bioengineered and does not contain mutant forms of the proteins,'' said Dr. Bhatnagar. ``On the other hand, they contain live toxins which make the vaccine produce side effects.''

The three antigens that produce the anthrax toxin complex are harmless individually. Toxins are produced only when two antigens combine. Protective antigen along with oedema factor causes swelling and redness of the skin. Similarly, protective antigen along with lethal factor produces lethal toxin. In either case, protective antigen is indispensable to produce a toxin. This is because the protective antigen first attaches itself to the cell receptors found on any human cell. Seven such protective antigens bind in a doughnut shape and in turn provide a base for either the oedema factor or lethal factor to bind on it. Once this binding is complete it penetrates into cell and starts its course of wreaking havoc on the cell ultimately leading to its death. Thus, the protective antigen alone cannot penetrate the cell and kill it nor can the other two toxins do it in the absence of the protective antigen.

The vaccine developed by Dr. Bhatnagar and Dr. Singh has made all the three antigens non-toxic by mutating it. The mutated protective antigen can neither attach itself to a cell surface nor can the seven protective antigens bind together in a doughnut shape. The other two proteins cannot bind to the protective antigen to penetrate the cell.

Plans are to first produce a vaccine with only the mutant protective antigen. But will the efficacy of a vaccine not be better if all the three mutant antigens are present in the vaccine? ``Yes, it will be better if all the antigens in a mutant form are present in the vaccine,'' said Dr. Bhatnagar. ``Such a vaccine can be produced anytime by introducing the other two antigens in the vaccine. This is possible since we have the mutant forms of all the three antigens.'' Efforts are on to produce a vaccine that contains only the mutant protective antigen.

Anthrax vaccine has already been produced at a laboratory scale. First, the mutant forms of the proteins are produced and then introduced into E.coli bacteria which in turn are allowed to multiply in number in a fermenter thereby increasing the amount of mutant proteins produced. About 25 gm. of the mutant protective antigen is produced everyday at the JNU. ``This amount is sufficient to produce about 10 million vaccines every day. The productivity is unprecedented in the world,'' said Dr. Bhatnagar. A vaccine requires about 2.5 micrograms of mutant antigen.

Anthrax is a curable infection provided treatment is given on time. Any delay in treatment can prove fatal. Hence the need for a vaccine with no side effects, Dr. Bhatnagar said.

At present testing on animals has been carried out using lethal dose of purified toxin. Human trails are yet to be undertaken.

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