Abstract
Background: Concomitant with the advent of molecular biology techniques and the ability of immunoglobulins (Ig) to recognize proteins, carbohydrates, lipopeptides and nucleic acids, vaccinologists have taken advantage to develop a variety of prophylactic and therapeutic vaccine prototypes. Presentation of epitopes to the immune system by Ig molecules as a carrier platform offers several advantages: (i) long exposure of the antigen to antigen processing cells (APCs) by virtue of their long half life, (ii) lack of the immune response to self Ig, focusing the immune response to protective epitopes rather than irrelevant epitopes, (iii) it takes advantage of the properties of Pc fragment of various isotypes like crossing the placenta (IgG) or homing in epithelia (IgA), and (iv) targeting various antigens by virtue of their binding specificity. Objectives: This study was aimed to genetically and enzymatically engineer immunoglobulins (Igs) able to express and to deliver concomitantly immunodominant T and B viral epitopes. Study design: Using a genetic engineering approach we replaced the complementary determining region 3 (CDR3) and complementary determining region 2 (CDR2) of an anti-arsonate 91A3 mAb with the immunodominant HA110-120 T cell epitope and HA150-159 B cell epitope of hemagglutinin (HA) of influenza A/PR8 virus, respectively. The second doubly antigenized Ig (Ig-HA-Gal-B) was constructed on an Ig in which CDR3 was replaced with HA110-120 T cell epitope while the HA150-159 B cell epitope was enzymatically assembled through an imidic bond on the galactose (Gal) residues of the carbohydrate moiety. Results and conclusions: Both genetically and genetically/enzymatically doubly antigenized Ig constructs (dAIg) were properly folded and they were able to activate peptide-specific T cells and to elicit anti-viral antibody response in mice. This demonstrates that the CDR loops as well as carbohydrate moieties of immunoglobulins represent permissive sites for grafting foreign epitopes without altering the structural integrity of immunoglobulins and the immunogenicity of the viral peptides.
Original language | English |
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Pages (from-to) | 85-95 |
Number of pages | 11 |
Journal | Immunotechnology |
Volume | 2 |
Issue number | 2 |
DOIs | |
State | Published - Jun 1996 |
Externally published | Yes |
Keywords
- Antigenized immunoglobulins
- Enzymatic engineering
- Genetic engineering
- Influenza virus
- Viral epitopes