Multiple sources of evidence indicated a role for vaccine-induced antibody responses targeting the V2 region of the envelope glycoprotein (Env): (1) the case-control study of immune correlates of risk showed that the magnitude of IgG antibodies binding to the V1/V2 region of Env was inversely correlated with risk of infection [2–5]; (2) the magnitude of binding of IgG antibodies to linear peptides in the V2 loop was inversely correlated with risk of infection [3,6]; and (3) sieve analysis targeted to the V2 region (described below) demonstrated vaccine pressure at two sites [7]. This evidence concerns the gene ERVW-1 and infection.