Group A rotaviruses (RVAs) are a primary cause of gastroenteritis in children under 5 years of age and are associated with over 500,000 deaths annually, of which the majority occur in developing countries (42, 43). RVAs belong to the family Reoviridae, and the infectious RVA virion is a triple-layered icosahedral particle that contains 11 segments of double-stranded RNA (18). The outer capsid layer is composed of the spike protease-sensitive attachment protein VP4 (P) and the glycoprotein VP7 (G). The nucleotide sequences of the VP7-and VP4-encoding segments form the basis of a dual classification system that defines the G and P genotypes of RVAs, respectively. Although 27 G genotypes and 35 P genotypes have been identified to date (31), only a few RVA G and P genotype combinations contribute substantially to the burden of human disease (29,30,32,53 (33,35). An increase in prevalence of G12 RVAs, mainly associated with P[8] or P [6] and to a lesser extent with P[4] or P[9] VP4s, was observed around the turn of the century. The G12 RVA strains are now considered the sixth common global genotype (29,33,35,49).Two live attenuated oral RVA vaccines, Rotarix (GlaxoSmithKline Biologicals, Belgium) and RotaTeq (Merck & Co., Inc., United States), have been licensed for use in many countries around the world. Rotarix is derived from the attenuated human G1P[8] RVA strain 89-12, which was isolated in Cincinnati, OH, in 1988 (65). RotaTeq contains five human-bovine reassortant RVA strains (WI79-9, SC2-9, WI78-9, BrB-9, and WI79-4, referred to as G1, G2, G3, G4, and P1 reassortants, respectively, for simplicity). The G1 to G4 reassortants each express one of the VP7 proteins of the human RVA parental strains WI79 (G1), SC2 (G2), WI78 (G3), and BrB (G4) and the VP4 protein of the bovine RVA strain WC3 (P7[5]), whereas the P1 reassortant expresses the VP4 protein of the human RVA strain WI79 (P1A [8]) and the VP7 protein of the bovine RVA strain WC3 (G6) (9, 34). Human RVA SC-2 was isolated in 1981 at St. Christopher's Hospital of Philadelphia, and the WI79 and WI78 RVAs were isolated in 1983 at the Children's Hospital of Philadelphia, while the BrB (originally Bricout B) RVA strain was isolated in 1984 at L'Hôpital Armand Trousseau (Paris, France) (34). Both RVA vaccines have been proven to be safe and efficacious in large-scale clinical trials (9,51,59,61,62). The mechanisms by which the vaccines induce immunologic protection in infants have not been clearly elucidated. It likely includes the induction of serum and intestinal serotypespecific neutralizing antibodies directed against VP7 and VP4 and virus-specific cytotoxic T lymphocytes (20,63,64). However, proteins other than VP7 and VP4 may be involved in immune protection as well.