Dendritic cells (DCs) are involved in human and simian immunodeficiency virus (HIV and SIV) pathogenesis but also play a critical role in orchestrating innate and adaptive vaccine-specific immune responses. Effective HIV/SIV vaccines require strong antigen-specific CD4 T cell responses, cytotoxic activity of CD8 T cells, and neutralizing/non-neutralizing antibody production at mucosal and systemic sites. To develop a protective HIV/SIV vaccine, vaccine regimens including DCs themselves, protein, DNA, mRNA, virus vectors, and various combinations have been evaluated in different animal and human models. Recent studies have shown that DCs enhanced prophylactic HIV/SIV vaccine efficacy by producing pro-inflammatory cytokines, improving T cell responses, and recruiting effector cells to target tissues. DCs are also targets for therapeutic HIV/SIV vaccines due to their ability to reverse latency, present antigen, and augment T and B cell immunity. Here, we review the complex interactions of DCs over the course of HIV/SIV prophylactic and therapeutic immunizations, providing new insights into development of advanced DC-targeted HIV/SIV vaccines.
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