Even after almost 30 years of HIV research and the ongoing search for correlates of protection, there is still a critical need to determine how effective different types of antibody effector mechanisms can be in prevention of HIV-1 infection. Although many groups have tried to identify which neutralization assay can predict in vivo protection, this issue is still open to debate [33] . In several SIV and SHIV macaque studies neutralizing mAbs have correlated with protection [34, 35, 36, 37, 38, 39, 40, 41, 42, 43] , but there are also multiple counter examples [44, 45] . In this context, the most compelling demonstration that pre-existing Abs can be protective comes from passive immunization studies with either IgG or mAbs [28, 34, 38, 39, 40, 41, 42, 43, 46, 47, 48, 49] . The most recent study uses the HGN194 mAb against a SHIV strain containing an 'early' envelope and emphasizes the importance of potent neutralizing Abs that confer protection against a heterologous mucosal challenge [4] . The latter is highly significant since future vaccines will need to be effective against these relatively resistant early founder strains before infection is established in vivo [50] .