The overlapping Fluoro Sorafenib representation of antigenic VP4 capsid genotypes in rotaviruses with distinct VP7 capsid genotypes, which was demonstrated in this archival study and is also currently observed, further supports rotavirus vaccine development strategies [6], [9], [51]. It is important to note that both multivalent (RotaTeq: attenuated reassortant with human G1, G2, G3, G4, and P[8] antigenicity in a bovine backbone) and monovalent (Rotarix: attenuated human G1P[8]) vaccines have reduced the burden of rotavirus disease in countries where vaccination programs have been implemented [52]. Although the composition of RotaTeq and Rotarix differ both in valency and source of viral strain (i.e.

a reassortant with bovine backbone or an attenuated human strain), they have similar efficacies against severe rotavirus gastroenteritis, indicating that the relative importance of VP7 and VP4 antigenicity is unclear [53]. Moreover, the first live, attenuated rotavirus vaccine, RRV-TV, composed of a closely homologous simian backbone strain, including a simian VP4, was efficacious against severe rotavirus gastroenteritis [54]. Regardless of the specificity of vaccine formulations implemented to protect against the conserved VP7 and VP4 genotypes, additional surveillance data will need to be analyzed in the post-vaccine era to determine whether rotavirus evolution differs with the widespread introduction of vaccines [51]. On the other hand, noroviruses exhibit a large reservoir of genetic diversity, and our current understanding of this diversity may be limited, as evidenced by the presence of unique variants (and possibly new genotypes) detected in this cohort (KL45 and T091).

Although KL45 and T091 have not been detected in current epidemiological surveys, strain C127 is an archival representative of the highly prevalent contemporary genotype GII.4, indicating that GII.4 noroviruses have maintained importance in the norovirus repertoire over more than 30 years. Thus, vaccination efforts against GII.4 noroviruses may be necessary. Several groups are currently investigating norovirus vaccine formulations for noroviruses and recent advances have been made particularly in GII.4-specific antibody epitope mapping [55]�C[60]. However, formulation of a cross-genotype, broad-spectrum norovirus vaccine is complicated by the lack of biological data, namely, it is unknown whether the designated VP1 capsid genotypes correlate with serotype specificity. Some insight was provided by a cross-challenge study in human volunteers, which demonstrated the importance of norovirus genogroups in protecting against disease, when administration of a GI.1 norovirus Batimastat failed to confer protection upon cross-challenge with a GII.2 norovirus [61].