The recent Keystone Symposia meeting on HIV Vaccines was held on 21-26 March 2012 in Keystone (CO, USA) back-to-back with the Viral Immunity meeting, creating synergy between the two areas of research. In this short report of the meeting, the authors will highlight three areas of interest that emerged from the two meetings: the recently emerging role of NK cells in modulating dendritic cell function, new data on the importance of dendritic cell antigen processing on priming of adaptive immunity and intriguing data suggesting that narrow targeting of very few protective epitopes restricted by a single MHC class I allele might be sufficient to mediate control of otherwise highly pathogenic SIV infection.