Though the IgG3 responses reported here do not include HIV-1 infected cases from RV144 by design, we hypothesize that the vaccine recipients with very low V1V2-specific IgG3 were at higher risk of infection and that the comparatively low frequency of these participants in HVTN 097 and HVTN 100 may indicate comparatively lower risk of infection. This evidence concerns the gene IGHG3 and infection.