Antigenicity and immunogenicity

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Chapter: Pharmaceutical Drugs and Dosage: Protein and peptide drug delivery

The ability of a protein to generate an immune response, triggering the production of antibodies, is referred to as immunogenicity.


Antigenicity and immunogenicity

The ability of a protein to generate an immune response, triggering the production of antibodies, is referred to as immunogenicity. Sometimes, the first administration of a protein does not elicit an immune response due to low concentration or longer time required for the humoral and cellular immune processes. Repeated protein administration may often lead to the formation of antibodies, causing an immune reaction.

 Antigenicity, on the other hand, refers to the ability of specific sites (epitopes) on the protein to recognize antibodies in the host immune system. Thus, the first administration of an antigenic protein would lead to an immune reaction if the host immune system has antibodies against the for-eign protein epitope. When antibodies are developed upon repeated protein administration (immunogenicity), the protein may not be antigenic when administered first but becomes antigenic upon subsequent administration when the host has formed mature antibodies against the protein.

Although proteins made in a particular organism are recognized by the immune system as self-protein and normally do not elicit an immune response, misfolded or denatured forms of self-proteins may be immunogenic. Thus, immunogenicity may be prevented by maintaining the molecule in the properly folded native conformation as well as by minimizing or preventing protein self-association. In general, the recombinant DNA-produced proteins are likely to be relatively more immunogenic compared to the natural pro-teins. Approaches toward humanizing antibodies or adding specific human sequences to murine antibodies to make chimeras have greatly improved their therapeutic potential by reducing or eliminating their immune response.

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