日本質量分析学会 第67回質量分析総合討論会

演題概要

ポスター発表

第1日 5月15日(水)  P会場(多目的ホール)

異なる緩衝剤中での抗体の安定性と構造の関係

(1阪大院工2自然科学研究機構)
o尾山博章1榎本敢太1鳥巣哲夫1内山進1,2

Introduction
It has been recently recognized that antibody aggregates may result in adverse effects such as immunogenicity and decrease in drag efficacy. Thus, formulation optimizations of antibody drugs are necessary to minimize aggregation. Mechanistic understanding of buffer contribution to the stability could pave the way for the rational formulation development.
Results
Higher aggregation propensity was observed in citrate buffer. Zeta potential of antibody molecule in citrate buffer was lower than that in acetate buffer. Secondary virial coefficient showed repulsive interaction between antibody molecules in acetate buffer while attractive interaction in citrate buffer. HDX-MS detected some regions with less conformational flexibility in citrate buffer than acetate buffer.
Discussion
Lower absolute value of zeta potential in citrate buffer suggested, upon binding of citrate ions which has higher valence number than acetate ions on antibody molecules, leading to higher shielding effect of the ions. This preferential binding of citrate ions could cause structural change on specific regions, which induce difference of interaction. Higher aggregation property in citrate buffer could be attributed to attractive interaction between antibody molecules. In conclusion, aggregation difference between acetate buffer and citrate buffer was rationally explained by biophysical parameter.