Chapter 27. HIV Vaccine Development: From Empiricism to Medicinal Chemistry

Abstract

Publisher Summary This chapter reviews the recent developments in adjuvant technology, antigen presentation, and vaccine delivery and also presents their impact on the development of a human immunodeficiency virus (HIV) vaccine. The isolation and identification of HIV as the etiologic agent for AIDS have been several important milestones toward the development of HIV vaccines. Yet, HIV continues to be an imposing foe for vaccine developers. This is due in large part to two principal issues—HIV variation and HIV transmission. Worldwide isolates of HIV are quite variable, particularly in immunodominant regions likely to be associated with protective immunity; thus, vaccine developers face a moving target of antigenic drifting. Moreover, the routes of HIV transmission, predominantly sexual transmission along with perinatal and intravenous, provide a variety of obstacles to vaccine development. As a result, there has been a tremendous push toward the new strategies for antigen presentation, adjuvant development, and vaccine vehicles. From low tech killed vaccines to high tech biolistic genetic immunization, multiple strategies are being utilized aiming at the prevention of HIV. Recently, novel strategies have been developed for induction of cytotoxic T cells by the modification of protein and peptide antigens. These strategies are now actively pursued in HIV vaccine development. Antigen presentation strategies are also utilized to optimize humoral immune responses against HIV and related retroviruses, leading to innovative vaccine candidates. In addition to accelerating the development of effective HIV vaccines, it is likely that this renewed emphasis on novel approaches to potentiate immune responses of experimental vaccines can lead to the development of effective vaccines against several other important infectious diseases.