Peptide Knowledge Center

Research progress of synthetic peptide vaccine

Infectious diseases, such as hepatitis, influenza, malaria, schistosomiasis and other viral or parasitic infectious diseases, are widely spread and more people are infected by them. At present although there are chemotherapy drugs that can be used to treat and have good curative effect, the reinfection rate after cure is very high, and the reinfected people need to be treated continuously in the epidemic area, In order to prevent and cure these infectious diseases fundamentally, we must rely on vaccines.  There are more researches on vaccines for parasitic and viral diseases now

With the development of biochemical technology, more and more soluble antigens of infectious diseases have been identified, which can induce animals to produce protective antibodies. These antigens are usually proteins (including enzymes) or glycoproteins, which can be used as candidate proteins for vaccines. In order to solve the source problem of these proteins, genetic engineering recombinant vaccines have been developed, In recent years, anti idiotypic antibody vaccine and DNA vaccine have been developed.

In the early 1980s, Lerner proposed the method of developing synthetic peptide vaccine: firstly, the amino acid sequence of natural antigen (such as virus or its subunit) was determined, and the epitope peptide was found; 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 causing infection. Therefore, people have no idea about the highly dangerous infectious diseases, such as AIDS

We dare not use inactivated or attenuated vaccines. For this kind of diseases, it is particularly important to develop synthetic peptide vaccines.

  • Determination of antigenic determinant peptide

The most important step in the study of synthetic peptide vaccine is to find antigenic determinants. 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 its antigenic determinant, or antigenic site. Antigen sites are composed of some amino acid residues that play a binding role. 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 called continuous antigen sites, also known as sequence antigen sites or discontinuous antigen sites, Also known as conformational antigenic sites.

Continuous antigens are usually short linear polypeptide fragments in a protein. They can bind to antibodies induced by intact protein. However, because they usually can not maintain the conformation of intact protein, sometimes their binding may be weaker than that of intact protein. Discontinuous antigen is 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 residue of the antigenic determinant maintains its original intrinsic conformation in the protein, can the antigenic determinant bind to the antibody that binds to the antigenic site. 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 at discontinuous antigen sites.

Methods of finding antigenic determinants:

1.Enzymatic and chemical cleavage of protein fragments

This is the first method to determine the antigenic determinants. The antigenic molecules with good immune effect and known primary structure are hydrolyzed into multiple polypeptide fragments by enzymolysis or chemical cleavage, and then the antigenicity and immunogenicity of the obtained polypeptide are determined, from which the effective antigenic peptides can be determined and used to prepare vaccines

2.Deductive method

In order to find out the region of antigenic determinant accurately, a deductive method was developed to predict antigenic sites by analyzing the hydrophilicity, mobility and accessibility of antigenic protein according to its amino acid sequence.

3.Chemical peptide synthesis

Although deductive method can predict the antigenic sites of proteins, its accuracy is usually only 70% - 80%, which will not only make some predicted antigenic sites have no antigenicity and immunogenicity, but also inevitably make some effective antigenic sites missing, It is very easy to synthesize a large number of polypeptides in a short time, which makes people begin to search for effective antigenic peptides by chemical synthesis of polypeptides.These methods include synchronous multi needle peptide synthesis, peptide scanning and light guided localization synthesis.

  • Common synthetic peptide vaccine antigens

The key to the study of synthetic peptide vaccine is to prepare peptide antigen with good immunogenicity and non-toxic side effects, and use adjuvant to get better immune effect, However, there are several kinds of synthetic peptide antigens:

Antigen peptide carrier complex antigen

In the initial stage of synthetic peptide vaccine, except for the large peptide (molecular weight more than 5000) obtained by enzymatic and chemical cleavage, which can be directly inoculated with antigen, the others are inoculated with antigen peptide carrier complex as antigen, In order to enhance the immune effect, glutaraldehyde and other linkers were used to attach effective antigen peptides to carrier proteins ovalbumin (OVA), bovine serum albumin (BSA) and tetanus toxoid (TT).

Multiple antigenic peptide antigen

There are carrier proteins in the antigen peptide carrier complex antigen, which are usually allogeneic proteins, so it is easy to cause inflammation or allergic reaction during inoculation, and also affect the specificity of antigen peptide, At present, the following methods are mainly used to improve the synthesis of peptide vaccine antigen by increasing the repeat times of peptide to increase the molecular weight of antigen

They include polypeptide antigen, tandem peptide antigen, chain and circular dimer peptide antigen containing disulfide bond, dendrimer antigenic peptide, dendrimer antigenic peptide containing tandem peptide, etc

Multivalent synthetic peptide vaccine antigen

At present, most of the studies are synthetic peptide antigens of single antigenic peptide or its polymers, which only represent one antigenic site, and the induced protection is not very ideal. If several effective antigenic peptides are selected from different effective antigenic molecules, and then these antigenic peptides representing different antigenic sites are used to make multivalent synthetic peptide vaccines, the immune protection will be increased

As a direction of vaccine research, synthetic peptide vaccine is still in the stage of development, but some gratifying research results have been obtained. For example, synthetic peptide vaccine for malaria and family planning has entered the phase I and II clinical stage, and has been tried in some African countries, People often need to vaccinate a variety of vaccines. Synthetic peptide vaccine can assemble the effective antigenic peptides of a variety of diseases together to prepare an antigen containing a variety of antigenic peptides of infectious diseases, which can form a combined synthetic peptide vaccine, Combined synthetic peptide vaccine may become an important development direction of synthetic peptide vaccine in the future.

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