Progress and challenges toward an AIDS vaccine: Brother, can you spare a paradigm?

The development of a safe and effective vaccine for prevention of AIDS has thus far proven to be exceedingly difficult due to the complexities associated with HIV pathogenesis including but not limited to antigenic hypervariability, multiple routes and modes of transmission, a lack of defined correlates of protective immunity, and a tropism for infection of immunoregulatory cells which are essential for orchestrating an effective host immune response. Recent observations, including the identification of significant differences between primary isolates of HIV circulating in the population and laboratory-adapted isolates, animal model protection studies demonstrating prevention of AIDS-like disease progression in nonhuman primates in the absence of sterilizing immunity, and epidemiologic studies which question the current dogma surrounding HIV variation and control, have led to the development of novel approaches for antigen presentation and adjuvant development targeted at AIDS vaccine development. The goal of developing a safe and effective AIDS vaccine will likely occur when continued advances in understanding the immunopathogenesis of HIV is balanced with a healthy dose of empirical testing of innovative candidate AIDS vaccines.