Chimeric Antibody Against Encephalitis
Preclinical studies of a new drug for tick borne encephalitis Encemab developed by scientists from the Institute of chemical biology and fundamental medicine of the Siberia Department RAS (Novosibirsk) have been completed. The studies have shown that the new drug is thousands of times more effective versus human immunoglobulin serum, it is not toxic and safe for patients.
Encemab is developed from a chimeric antibody for tick-borne encephalitis. It is based on monoclonal antibodies, that in a large panel had been developed at the ICBFM a few dozens of years ago.
Nina Tikunova, MD, PhD, Biol., head of laboratory of molecular microbiology at the ICBFM SD RAS, said that effects of the drug have been checked for acute prevention. Mice received lethal doses of tick-borne encephalitis virus and in one day – antibodies at doses of and 1 micrograms per kg body weight, and in all cases 100% of mice survived. The immunoglobuline serum led to survival of mice only in 10% of cases.
Tests performed by ICBFM researchers together with their colleagues from the Tomsk affiliate of research and manufacturing association Microgenom, Russian Ministry of Health, and Tomsk affiliate of the M.M. Shemyakin and Y.A. Ovchinnikov Institute of Bioorganic Chemistry, RAS (Puschino), supported specific antiviral activity of the drug, to study pharmacokinetics, acute and subchronic toxicity and immunological safety.
At the stage of assessment of antiviral activity it was observed, that the chimeric antibody may be effective both as acute prevention and therapeutic agent. That is why the scope of clinical studies increased to assess chronic toxicity of single and multiple doses. In both cases pharmacokinetics for intravenous and intramuscular routes of administration had to be studied, thus dividing preclinical studies into four parts..
Toxicity studies were performed at affiliate of the Institute of Bioorganic Chemistry RAS, Puschino. The effects of the drug were compared against human tick-borne encephalitis immunoglobulin (solution for injections manufactured by the FSUE NPO Microgen, Russian Ministry of Health). Encemab was evaluated at two dose levels, 10-fold and 20-fold exceeding the therapeutic dose. The drug did not show any acute and chronic toxicity. To support the evidence obtained, tests had to be repeated. A 10-fold and 100-fold doses were taken. The drug still was safe. A 1.5 dose of serum immunoglobulin was administered to control laboratory mice. Some of mice died, and surviving mice had bristled fur.
Pharmacokinetic characteristics of Encemab are similar to other marketed antibody products. The drug did not affect the immune response either.
As a conclusion, Nina Tikunova said that Encemab is comparable to human tick-borne encephalitis immunoglobulin. The new drug acts at small doses, contains the sole specific antibody, has high specific activity and does not require donor blood for production, neither from animals, nor form humans.
Preclinical studies of the drug are completed. The drug may be registered at the Ministry of Health to obtain approval for phase one clinical trials.