Importantly, antibody-mediated antigenic drift of GII.4 strains coupled with both mucosal IgA and T cell responses in challenged but uninfected volunteers strongly support the existence of longterm protective immunity against norovirus strains. In fact, the unique antibody reactivity patterns characterized herein are most likely explained as an archeological immune record of successive waves of contemporary GII.4 infections in this individual over time, implying that successful vaccine design is possible, as previously proposed by our group and others [37, 44, 54] .