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Existing RV vaccines are successful in many developed countries, but their efficacy remains poor in developing countries, which could be due to lack of cross protection between RV genotypes more common in developed countries and other P-type RVs less common in developed countries but common in developing countries. In this study, crystal structures of major P[II] genogroup VP8* receptor domains in complex with Lewis epitope\u2013containing histo-blood group antigen (HBGA) glycans were determined, revealing the structural basis for RV HBGA receptor specificities that determine RV host ranges. 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