Tetanus monoclonal antibody is expected to become mainstream drugs

Recently, "Cell Report" published a research result on tetanus monoclonal antibody from the team of Professor Liao Huaxin of Jinan University and Tsinghua University, TechnoMicrobiology and other institutions
.
The study shows that as a new generation of tetanus prevention and treatment drugs, tetanus monoclonal antibody has great potential for development in China.

According to the researchers, they extracted about 32 strains of antibodies from the blood of a volunteer who had been actively immunized with a tetanus toxoid vaccine every 10 years for 40 years.
And test, screened out 4 strains of potent antibodies with strong affinity to tetanus toxin, namely TT0069, TT0155, TT0170 and TT0067
.

Subsequently, the researchers found in a mouse toxicity neutralization test at a dose of 60LD50 toxin that the minimum dose of TT0067 to completely neutralize the lethal dose of tetanus toxin is 6.
67μg, while the other three such as TT0069 only need 2.
22μg
.
By further comparing the neutralizing ability of TT0069 and HTIG for tetanus toxin, the researchers found that under the condition of 10LD50 toxin dosage, the titre of TT0069 for the complete protection of immune tetanus toxin-related symptoms is about 60μg/kg, while HTIG requires 50IU/kg

Further studies on the structure of 4 kinds of antibodies and tetanus toxin show that tetanus toxin contains three functional areas, namely segment A, segment B and segment C, of ​​which segment C has been confirmed to be the result of tetanus toxin infecting neuronal cells.
The main factor, at the same time, the C segment is also the binding site of tetanus monoclonal antibody TT0067
.

Previous studies on tetanus toxin have found that tetanus toxin requires its C segment to bind to the ganglioside lipopolysaccharide receptor GD1a and GM1a on the surface of nerve cells to exert toxicity
.

In the study of tetanus monoclonal antibody, the researchers obtained the co-crystal structure of TT0067Fab and the C segment of recombinant tetanus toxin, and found that TT0067Fab can replace the GD1a receptor of ganglioside and bind to the C segment of tetanus toxin, thus acting Effectively neutralize the effects of toxins
.

In addition, the researchers also found that the structure and dosage of tetanus monoclonal antibody showed its high efficiency in neutralizing tetanus toxin
.
Compared with the traditional blood products TAT ​​and HTIG, the production capacity of tetanus monoclonal antibody is not restricted by the amount of plasma collection, which can meet the domestic demand for safe passive tetanus immune preparations on a large scale

Related paper information: https://doi.