Human Immunodeficiency Virus Type 1 Vaccine Development: Recent Advances in the Cytotoxic T-Lymphocyte Platform “Spotty Business”

For human immunodeficiency virus type 1 (HIV-1) vaccine development, a central focus is developing a vaccine that primarily drives strong and broad CD8 ϩ cytotoxic T lymphocytes (CTLs).This focus is largely due to the difficulty in generating cross-neutralizing antibodies against the diverse array of HIV viral envelopes (9,40,78, 139).The ability of CD8 ϩ T cells to impact or control viral replication is supported by model primate studies and is reiterated by studies of immune control in infected individuals.For example, Cao et al. ( 28) reported that HIV-1-infected long-term nonprogressors exhibited high levels of HIV-specific CTLs.In addition, HIV-1-infected patients with high levels of virus-specific CTLs exhibited lower viral loads, slower CD4 ϩ T-cell declines as measured in peripheral blood, and relatively stable clinical statuses (23,81, 108, 112).Preclinical studies conducted with simian immunodeficiency virus (SIV)-infected monkeys showed that upon their in vivo depletion of CD8 ϩ T cells, a rapid and dramatic increase in viremia was observed (70, 131).While no correlates of immunity for protection against HIV-1 have been concretely established, these data as well as those of others (6, 13, 137) strongly suggest that CD8 ϩ T cells are important in controlling viral infection and may be an important component of an effective HIV-1 vaccine.In this review, we summarize recent advances in HIV vaccine development utilizing various platforms that target the induction of cellular immunity.In particular, we draw inferences, as appropriate, for the induction of cellular immune responses at mucosal as well as systemic sites.