Oral immunization induces an effective mucosal immune response that protects mice against intravaginal HSV-2 challenge

Immunity against genital Herpes Simplex Virus 2 (HSV-2) infection is dependent on local memory immune responses in the genital tract. Oral immunisation can induce mucosal immune responses in the genital tract but has not been tested against viral STIs. Here we describe the mucosal immune responses elicited by an oral vaccine that protects mice against intravaginal challenge from lethal HSV-2 infection. Control of HSV-2 was attributed to  HSV-2-specific IgG and IgA in the genital mucosa together with CD4 and CD8 T cells recruited to the genital epithelia. Furthermore, combining this vaccine with vaginal application of DNFB to induce transient local inflammation led to the recruitment of CD8 tissue resident memory cells in the genital epithelia that controlled new infection with HSV-2. Thus, this represents the first oral vaccine that can protect mice against lethal intravaginal HSV challenge.