Deciphering the rule of antigen-antibody amino acid interaction

Abstract Antigenic drift is the biggest challenge for mutagenic RNA virus vaccine development. The most fundamental but neglected thing is to determine the immune escape mutation map (IEMM) of 20 amino acids to reveal the rule of the viral immune escape. We use universal protein tags as a linear epitope model to determine the relationship between the epitope mutation and immune escape. To describe and draw amino acid interaction maps, mutations of protein tags are classified into four types: IEM (immune escape mutation), ADERM (antibody-dependent enhancement risk mutation), EQM (equivalent mutation), and IVM (invalid mutation). To make up for the data limitation, the amino acid interaction pairs determined by 3D structure through literature search are simultaneously used to form a more systematic and universal antigen-antibody interaction maps. The results are: (i) one residue interacts with multiple amino acids in antigen-antibody interaction; (ii) Most amino acid replacements are IVM and EQM. (iii) Once aromatic amino acids replace non-aromatic amino acids, the mutation is often inactive. (iv) Substituting residues with the same physical and chemical properties easily lead to IEM. Therefore, this study had important theoretical significance for future research on antigenic drift, antibody rescue and vaccine renewal design. Importance We typed the antigenic epitope mutations into IEM, ADERM, EQM, and IVM types to describe and quantify the results of antigenic mutations. According to the results, the antigen-antibody interaction rule was summarized as one-to-many interaction rule. To sum up, the Epitope mutation rules were defined as IVM and EQM predomination rule, aryl mutation escape rule and homogeneous mutation escape rule.