Epitope mapping of botulinum neurotoxins light chains

Abstract

Botulinum neurotoxins (BoNTs) are listed among the most potent biothreat agents. Simultaneously, two out of seven known serotypes of these toxins are used in medicine and cosmetics. This situation calls for development of detailed epitope maps of these toxins. Such maps will help to develop new ways for decreasing damage caused by these toxins if they were to be used as weapons while retaining the therapeutic effect of these toxins used as medicine. Here, we used a library of random fragments of DNA encoding the catalytic domain of botulinum neurotoxin serotype A to identify short epitope-forming sequences. We demonstrated that knowledge of such sequences in a BoNT of one serotype can be used for identification of epitope-forming sequences in other serotypes of BoNTs. We also demonstrated a serodiagnostic value of identified sequences and their ability to retain epitope-specific structures and trigger production of corresponding antibodies, even when they are transferred into a background of a completely alien carrier protein.

Development of neutralizing scFv-Fc against botulinum neurotoxin A light chain from a macaque immune library

“…The large, seven aa epitope identified for SEM95-C6 is part of four discrete regions within BoNT/A-L known to induce an immune response in rabbit. 42 This work showed that an antibody directed against this epitope is not neutralizing.…”

Solid–Liquid Phase Equilibria of the Aqueous Quaternary System K+, Mg2+//Cl–, SO42–-H2O at T = 363.2 K

“…The comparison of the phase diagrams of the system K + //Cl – , SO 4 2– -H 2 O at 348.2, 363.2, and 373.2 K has been done. The composition and solid phase of the invariant points are listed in Table , and the multitemperature phase diagram is shown in Figure .…”

“…Comparison of phase diagrams of the ternary system Mg 2+ //Cl – , SO 4 2– -H 2 O at 348.2, , 363.2, and 373.2 K …”

“…The comparison of the phase diagrams of the ternary system Mg 2+ //Cl – , SO 4 2– -H 2 O at multitemperature has been done. The composition of the invariant points is listed in Table , and the multitemperature phase diagram at 348.2, , 363.2, and 373.2 K is shown in Figure . As Table and Figure show, the ternary systems Mg 2+ //Cl – , SO 4 2– -H 2 O at 348.2 363.2, and 373.2 K all belong to a simple system without double salt and solid solution formed.…”

“…The results of parameter calculation are similar to those of experiments, and the applicability is good. However, the model lacks the interaction parameters of Cl – -SO 4 2– , so in this work, parameters W 1, aa’c , Q 1, aa’c , and Y 1, aa’c are fitted according to the ternary system K + //Cl – , SO 4 2– -H 2 O and Mg 2+ //Cl – , SO 4 2– -H 2 O at 273.2–373.2 K. ,− , The parameters (binary parameters, interaction parameters, and Ksp) are listed in Tables – . The interaction parameters W aa’c , Q 1, aa’c , and Y 1, aa’c of the ternary system K + //Cl – , SO 4 2– -H 2 O and Mg 2+ //Cl – , SO 4 2– -H 2 O and Ksp of the double salt KMg­(SO 4 )­Cl·3H 2 O are obtained by fitting the solubility data in this work, and other parameters are obtained from references. , The calculation formulas and the calculated values are listed in eq S1 and Tables S1–S3.…”