An effective vaccine against human immunodeficiency virus (HIV) should not only protect from infection and development of acquired immunodeficiency syndrome (AIDS), but also prevent potential transmission to naïve partners. We recently reported protection of rhesus macaques from chronic simian-human immunodeficiency virus (SHIV) infection and AIDS by an HIV envelope peptide-cocktail vaccine. In the present case study, we observed that one of the vaccinated females, with undetectable circulating virus, when housed in a pair with a naïve male, did not transmit the infection over a 35-week period of social contact. Subsequent experimental challenge of the male with the same SHIV strain resulted in high-level infection and transmission to its female cage-mate. However, the virus was undetectable in the female by 12 weeks without further vaccination, validating the multivalent peptide cocktail vaccine approach in the SHIV-rhesus model, and suggesting its potential utility as an HIV vaccine strategy for humans.