While the generation of bNAbs is considered a gold standard in vaccine-induced antibody responses, results from the RV144 trial showed that nonneutralizing antibodies directed toward the V1V2 loop of HIV-1 gp120, specifically the V2 loop region, were associated with decreased risk of infection, demonstrating the need for the development of Env immunogens that induce a broad anti-V1V2 antibody response. This evidence concerns the gene ITIH4 and infection.