Inadequate antigen presentation and/or suboptimal immunogenicity are considered major causes in the failure of human immunodeficiency vaccine to adequately protect against wild-type virus. Several approaches have been attempted to circumvent these hurdles. Here we reviewed some recent vaccinal strategies tested against the feline immunodeficiency virus and focused on: (i) improving antigen presentation by taking advantage of the exquisite ability of dendritic cells to process and present immunogens to the immune system; (ii) boosting immune responses with vaccinal antigens presented in a truly native conformation by the natural target cells of infection. Significance of the studies, possible correlates of protection involved, and implications for developing anti-human immunodeficiency virus vaccines are discussed. (C) 2009 Elsevier B.V. All rights reserved.