The potential protective role of broadly reactive, potent anti-Env neutralizing Abs (bnAbs) against HIV-1 infection at mucosal sites has been recognized for decades (Klein et al., 2013a, Moldt et al., 2012, Shingai et al., 2014, Liu et al., 2016, Hessell et al., 2009b, Barouch et al., 2013, Pegu et al., 2014, Stamatatos et al., 2009, Mascola and Haynes, 2013, Hessell et al., 2009a, Mascola et al., 2000, Veazey et al., 2003), but as yet no candidate vaccine tested has elicited these Abs in the circulation of HIV-1-uninfected persons. This evidence concerns the gene DDX41 and HIV-1 infection.