Chimpanzee Monoclonal Antibodies Protect Against Anthrax Challenge

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Chimpanzee Monoclonal Antibodies Protect Against Anthrax Challenge
2006
By Will Boggs, MD
J Infect Dis
NEW YORK (Reuters Health) Mar 31 - Chimpanzee monoclonal antibodies against anthrax toxin protect rats from anthrax toxin challenge, according to a report in the March 1 issue of The Journal of Infectious Diseases.
"For some of the diseases like this, active vaccination may not be the best choice because of the rarity of the disease," Dr. Zhaochun Chen from the National Institute of Allergy and Infectious Diseases, Bethesda, Maryland told Reuters Health. "Passive immunization with neutralizing antibodies in combination with antibiotics may be effective in treating this kind of disease."
Dr. Chen and colleagues identified potent neutralizing chimpanzee monoclonal antibodies against protective antigen, a receptor-binding protein of anthrax toxin, and tested its efficacy in a rat anthrax challenge model.
Two whole IgG1s constructed from chimpanzee single-chain variable fragments that inhibited anthrax toxin showed potent neutralization in a cell-based in vitro assay, the authors report.
Addition of one of these antibodies (W2) to protective antigen in a 1:4 ratio completely protected rats from anthrax toxin challenge, the results indicate. A similar mouse antibody protected only 1 of 3 rats in a similar challenge.
Single administration of both antibodies at 2:1 ratios protected 6 of 6 rats challenged with toxin at times ranging from 5 minutes to 1 week after antibody administration, the researchers found.
Even lower antibody:antigen ratios (0.5:1) still protected rats challenged 5 minutes or 4 hours later, the report indicates, but not when challenged a week later.
"Certainly, the efficacy of antibody-mediated protection will largely depend on the time to administer the antibody," Dr. Chen said.
"Antibodies are highly specific for bacterial toxins and, therefore, will not be expected to have side effects," Dr. Chen explained. "The antibodies we have generated were derived from chimpanzee for the Fab part, and the constant region of antibody was from human. As chimpanzee IgG sequence is almost identical to humans, we do not expect that our antibodies will elicit the immune response when they are used in humans."
The team is planning to test the antibodies in a rabbit model with anthrax spore challenge, which more closely reflects real-world infection, Dr. Chen added. "For these experiments, we want to know how long post-exposure that antibody is still protective (it will take time for spores to germinate and produce the toxins), and what is the minimal effective dose of antibodies."