Overcoming original (antigenic) sin

Original antigenic sin describes a phenomenon in which the antibody respons e elicited in an individual after a secondary viral infection reacts more s trongly to the viral variant that originally infected the individual. As T helper cells play critical roles in promoting antibody responses, a similar phenomenon may hold true for T helper cell responses. This concept is part icularly relevant to the development of vaccines. against viruses such as h uman immunodeficiency virus and hepatitis C virus, in which myriad viral va riants are present throughout the human population. We have compared the ef fects of priming the immune system with a single peptide epitope or with a cocktail of related peptides based on the epitope. Our data demonstrate tha t immunization with multiple peptide variants expands a more broadly reacti ve and durable T helper cell response than does immunization with a single peptide. This vaccine strategy may circumvent original antigenic sin. (C) 2 001 Academic Press.