A Novel Method for Designing Vaccines Against Constantly Mutating Pathogens
Eduardo A. Padlan
Marine Science Institute, College of Science
University of the Philippines, Diliman, Quezon City, Philippines
A method is described that could be used to design molecules suitable as vaccines for immunization, or for the generation of therapeutic antibodies against constantly mutating pathogens. The method consists of (1) locating the putative immunodominant epitopes of a protein antigen, and identifying the residues that contribute to the high antigenicity of the epitopes and (2) replacing those residues judiciously to reduce the antigenicity of the immunodominant epitopes, while preserving structure. The antibody response to the modified antigen would then be expected to be directed against more parts of the molecule, and not mainly against the formerly immunodominant epitopes. The method is also useful in the design of molecules suitable for immunization against pathogens that had been intentionally mutated so as to render those pathogens able to infect previously immune individuals.
Many pathogens are able to evade the immune system by constantly mutating their surface molecules. In so doing, the antibodies, which had been generated against previous strains of the pathogens, are no longer totally protective. In many instances, the pathogens are able to make the evasive move by mutating a few amino acids in a surface molecule that may contain several hundred residues.
Among the pathogens that are constantly mutating to achieve immune evasion are the influenza virus, the cold virus, and the virus that causes AIDS. These and other viruses and other pathogens have molecules on their surface, some of which are used to recognize and bind to the cells that the pathogens infect. Those surface molecules are the targets of the antibodies that our immune system produces to combat the pathogens. The external regions of those molecules can be used as vaccines. But a vaccine that utilizes a surface molecule, or part thereof, of a particular pathogen will be effective against mainly that pathogen, and may not offer protection against new or other strains of the organism.
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