With the development of immunology, it has been recognized that effective immunization means the participation of specific antigenic determinants with immunogenicity and protection. Therefore, in the early 1980s, Lerner proposed the method of developing synthetic peptide vaccine: firstly, determine the amino acid sequence of natural antigen (such as virus or its subunit), and search for antigenic determinant peptide; Then the peptide was synthesized, and its ability to induce antibody was tested, and the specific peptide with immunity and protection was selected to prepare vaccine. As a part of complete virus, peptide antigen has no risk of infectious diseases, and can be synthesized in large quantities, which has become one of the important ways of vaccine development in the future, However, it still has the possibility of infection. Therefore, people dare not use inactivated or attenuated vaccines for highly dangerous infectious diseases, such as AIDS. For such diseases, it is particularly important to develop synthetic peptide vaccines

Determination of antigenic determinant peptide

At present, we know that the antigenic reaction of a protein is the binding of some immunoglobulins recognized by the protein to the protein, and the binding region of the protein is the antigenic determinant of the protein, Antigen sites are composed of some binding amino acid residues. Because the binding is carried out in three-dimensional space, these amino acid residues can be continuous or discontinuous in the protein sequence. The corresponding antigen sites are correspondingly called continuous antigen sites, also known as sequence antigen sites; Continuous antigens are usually short linear polypeptide fragments in a protein. They can bind to antibodies induced by intact protein. However, they are usually unable to maintain the conformation of intact protein, Discontinuous antigens are formed by folding the polypeptide chain of a protein into a certain region of space. Only when the protein maintains its intrinsic conformation, or at least the amino acid residues of the antigenic determinant maintain their original intrinsic conformation in the protein, However, there are some exceptions in some cases. About 10% of the antibodies that can bind to discontinuous antigens can also bind to linear peptides composed of amino acid residues of discontinuous antigen sites

Enzymatic hydrolysis and cleavage protein fragment method

This is the first method to determine the antigen determinant cluster. The antigen molecules with good immune effect and known primary structure are hydrolyzed into multiple peptide fragments by enzymatic hydrolysis or chemical cracking method. Then the antigenicity and immunogenicity of the obtained peptides are determined, and the effective peptide segments are determined to prepare vaccine

Deductive method

In order to find out the region of antigen determinant cluster in protein, a deduction method for predicting antigen sites based on amino acid sequence analysis of antigen protein was developed

Peptide synthesis by chemical method

Although deductive method can predict the antigen sites of proteins, the accuracy of the method is usually only 70% - 80%, which will not only make some of the predicted antigen sites have no antigenicity and immunogenicity, but also inevitably some effective antigen sites will be missed. In recent years, with the development of combinatorial chemistry, the protein protein has been widely used in the future, It is very easy to synthesize a large number of peptides in a short time, which has prompted people to start to find effective peptide by chemical synthesis of peptides.