Avoiding deceptive imprinting of the immune response to HIV-1 infection in vaccine development

Lymphocyte clonal restriction is caused by priming the immune system with an antigen and has been referred to infectious disease study as "original antigenic sin" (OAS), described first for influenza by Francis [1]. OAS is a dominant feature of a normal immune response. Benefits of OAS come from the initial contact with the pathogen, which induces immunological memory. Memory is achieved by priming B and T cells of an immunologically naive host, and confers protection against infection with the antigen-related pathogen. Thus, a restricted antibody response to viral or parasite antigens is not per se pathogenic. However, the interplay between a "locked-in" immune response and the high genetic variation of the pathogenic agent can result in a deception of the immune system. In the following, clonal restriction of the immune response to HIV is described by giving examples of restricted anti-HIV antibody formation in maternally infected children. Clonal restriction results in host resistance of infected individuals to emerging HIV variants and quasispecies. The problems of classical approaches of vaccine design in AIDS and the lack of protection in vaccinated patients is reviewed.