On the other hand, newborns infected with other strains had high titers against 116E that did not differ significantly from the noninfected controls. strain 116E, a vaccine candidate, in its ability to evoke a potent RV-specific immunoglobulin A and neutralizing antibody response in serum and saliva among the infected babies. Our findings have important implications for the development of an effective RV vaccine. In India, where G9 strains are common in the community, the use of 116E as a vaccine, together with the rhesus tetravalent vaccine, may provide a broader protection against all the circulating RV serotypes, including serotype G9, which is not represented in the current rhesus RV tetravalent vaccine (G1-G4). The asymptomatic Amorolfine HCl nature of rotavirus (RV) infection in neonates has raised many questions and provided numerous insights into the pathogenesis of RV diarrhea in older children (15). Early observations that newborns infected with RV were protected against subsequent RV diarrhea provided evidence for natural immunity and laid the groundwork for the development of RV vaccines based on live attenuated strains (1a, 2). Similarly, the observation that primary RV infections Amorolfine HCl in children aged 3 to 24 months were associated with diarrhea whereas infections in neonates were usually asymptomatic suggested that understanding the difference between these infections might yield insights into an approach for preventing RV diarrhea. Initial attempts to explain the asymptomatic nature of neonatal infections were based on the hypothesis that neonatal RV strains were naturally avirulent and distinct from RVs that caused diarrhea in older infants and Amorolfine HCl children. This hypothesis was supported by the early discovery that RV strains isolated independently from newborns on four continents contained a distinct VP4 protein (P2A[6]) (8, 12). This protein, which is important in virus neutralization and virulence, was distinct from the VP4 proteins present in RV strains that caused diarrhea in older children (P1A[8] and P1B[4]) (12). Furthermore, in limited global surveys, RV strains with a distinct P serotype, P2A[6], were rarely found in older children with diarrhea. Two neonatal RV vaccines have been developed based on the potential avirulence of these neonatal (i.e., P2A[6]) strains (3, 22). Recently, we characterized RVs in diarrheal samples from Indian children and found an unusual diversity in strains (21). In contrast with earlier studies, P2A[6] strains were common among children with diarrhea, contradicting the earlier observation that these strains were naturally avirulent and found only in neonates. This observation suggested the need to examine other factors, including the levels of maternal neutralizing antibodies, which may be important in preventing symptomatic diarrhea in neonates. The present study took advantage of a long-term investigation of nosocomial RV infection among neonates born in the maternity unit at the All India Institute of Medical Sciences (AIIMS) in New Delhi that has been previously described (1a, 6, 16, 20). The purpose of this study was to compare the levels of cord blood neutralizing antibodies of the infected and noninfected neonates against the Amorolfine HCl four common RV serotypes as well as the AIIMS prototype neonatal strain, 116E, to determine whether the differences between the preexisting levels of neutralizing antibodies in the infected and noninfected neonates play an important role in prevention of neonatal RV infection. Further, we also assessed the breadth of immune response elicited by 116E-like strains by measuring the RV-specific immunoglobulin A (IgA) and neutralizing antibody Rabbit Polyclonal to DLGP1 response in serum and saliva samples of the infected and noninfected babies against common and neonatal RV strains. MATERIALS AND METHODS Subjects and study design. The study was conducted between June 1992 and March 1993 at the AIIMS, an urban hospital in.