More than 25 million people have died of AIDS as a result of infection with the human immunodeficiency virus (HIV), and between 36 and 45 million individuals are living with the virus. While HIV is rampant in sub-Saharan Africa and the Caribbean, there are growing epidemics in Eastern Europe and Central Asia. Despite significant advances in our understanding of the virus, increased public awareness and intervention, and the development of effective treatment regimens, the annual rate of new HIV infections threatens to increase around the world without some kind of novel intervention, according to recent projections by UNAIDS. There is, thus, a desperate need for the development of a preventative vaccine against HIV infection. HIV vaccine development has been hindered primarily by the difficulty of inducing antibodies capable of neutralizing the virus. Antibody-producing B cells recognize the variable loops of gp120, but the high error rate of viral reverse transcriptase (RT), along with the rapid turnover of plasma virions, provides a broad base of variants that escape detection by humoral immunity [1, 2]. The infidelity of RT during viral replication also promotes changes in envelope glycosylation patterns that render neutralization-sensitive domains inaccessible to HIV-specific antibodies [3–6]. In the simian immunodeficiency virus (SIV)/non-human primate model of HIV infection, no vaccine candidate to date has been shown to stimulate effective neutralizing antibodies capable of protecting its host against a heterologous virus challenge. Furthermore, a study in which neutralizing antibodies were passively transferred into rhesus macaques necessitated unreasonably high titers of antibody to achieve protection from infection [7]. Similar studies in HIV-infected humans have not only yielded very limited evidence of protection but have even suggested the promotion of viral escape [8]. Although efforts continue in the hope of developing an immunogen that will induce neutralizing antibodies, researchers have more recently focused on vaccine candidates that will primarily stimulate cellular immune responses against HIV. The cellular immune responses are known to provide effective control of several chronic human pathogens, including Epstein–Barr virus (EBV)[9, 10], cytomegalovirus (CMV)[11–13], and hepatitis viruses B [14–16] and C [17]. The cytotoxic CD8+ T lymphocytes (CTL) are thought to be the primary mediators of control of viral replication due to their ability to recognize and eliminate infected autologous cells. CD4+ T helper (Th) cells also play a critical role in protection from viral and bacterial pathogens, as these cells provide support for both cellular and humoral immune responses. The precise mechanism (s) of control in different pathogenic settings, however, remains elusive.

The SIV/rhesus macaque experimental system has provided compelling evidence in support of a role for T cells in the control of HIV/SIV replication. The depletion of CD8+ T cells during either primary or chronic SIV infection in Mamu A* 01-positive rhesus macaques is directly correlated to an increase in SIV viral load [18, 19]. In addition, the presence of vaccine-induced SIV-specific CD4+ and CD8+ T cells leads to a reduction in viral load during primary SIV infection [20–22]. A similar in vivo evidence in the setting of HIV infection has been difficult to