The purpose of this reissued Funding Opportunity Announcement (FOA) is to support high-risk, high-impact, early discovery research on vaccine approaches to prevent acquisition of or ongoing infection by HIV. In keeping with the high-risk, high-impact nature of this research, this FOA supports a Go/No-Go approach to funding high risk research, which is significantly different from most R01 projects. Continued funding for the full award duration is dependent upon achieving negotiated Go/No-Go criteria by the end of Year 2.