Richard Ward

..Even so, the Rotarix vaccine developed from attenuated 89-12 was found to elicit excellent protection against non-G1 rotaviruses...

..Human rotaviruses have also been developed as candidate vaccines and Rotarix, which is attenuated by passage in cell culture, has been launched in Mexico and may soon be available worldwide...

..Immune effectors have overlapping functions, and protection against rotavirus by either live or non-living vaccines is probably enhanced by this redundancy...

..In total, 16, 19, and 15 vaccine recipients had increases after 1, 2, and 3 doses, respectively, indicating that a 3-dose regimen increased the immune response elicited by this vaccine...

..This article describes the history of the development of the RIX4414 vaccine...

..The results of further research to elucidate the immunologic mechanism of protection will provide insight into improving the efficacy of current vaccines...

..In contrast to live rotavirus vaccines, CD4(+) T cells were found to be the only lymphocytes required for protection. If VP6 elicits comparable protection in humans, it would represent a potential second-generation vaccine candidate...

..These candidates are composed of single rotavirus strains and include the other vaccine being licensed worldwide (Rotarix). Studies that provide the basis for each approach will be presented and discussed...

..Cell-surface expression of the alpha2beta1-integrin plays a role in the mechanism that confers cholangiocyte susceptibility to RRV infection...

..Here, we investigate this question by examining the role of T lymphocytes in the destruction of extrahepatic bile ducts of neonatal mice using an experimental model of biliary atresia...

..The Mitogen Associated Protein Kinase (MAPK) signaling pathway can be activated by viral binding to cell-surface receptors. We hypothesized that RRV infection of cholangiocytes results in activation of MAPK signaling...

..RRV gene segment 4 plays a significant role in governing tropism for the cholangiocyte and the ability to induce murine BA. Gene segment 3 did not affect RRV infectivity in vitro but altered its in vivo effect...

..The objective of this study was to determine the effectiveness of the RotaShield vaccine against rotavirus gastroenteritis requiring hospitalization and to evaluate factors associated with vaccine receipt...

..These results indicate that strain-specific characteristics dictate tropism for cells of hepatobiliary origin which in turn impact the ability to induce the murine model of biliary atresia...

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..Vaccine virus was shed on days 3, 7 or 28 in 11/30 infants of the 116E and none in the other two groups. The 116E strain is attenuated, clinically safe and highly immunogenic with a single dose...

..As was previously found after oral and intranasal immunization, intrarectal immunization with MBP::VP6 and adjuvant was associated with T cell responses (IFNgamma and IL-17) but not B cell (antibody) responses...

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..05) protected. Intramuscular needle injection of VP6/LT(R192G)-plasmids also induced significant protection (66%)...

..This was not observed but instead the only VP6 epitope identified was AA(242-259), the dominant CD4(+) T cell epitope previously reported after oral, live rotavirus immunization...

..Thus, IFN-gamma was the only cytokine identified in stimulated CD4+ T cells from immunized mice that directly inhibited rotavirus replication...

..Together, these studies show that functional mapping is useful in locating epitopes that are relevant to the development of subunit rotavirus vaccines...

..Therefore, protection induced by intranasal immunization of mice with VP6 and adjuvant does not depend on intestinal rotavirus IgA antibody but appears to be associated with CD4 T cells...

..Thus, different adjuvants induced different degrees of protection and oral immunization was generally less effective then the i.n. route...

..n. immunization with EDIM or CJN VP6 was no different when the mice were challenged with McN, another strain of murine rotavirus. These results support further evaluation of VP6 as a vaccine...

..001 for each). These encouraging results have led to continued evaluation, in several countries, of a vaccine candidate derived from strain 89-12...

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..The results of studies in the adult mouse model that appear to be most pertinent to the present vaccine candidates are presented and discussed...

..No intussusception cases were reported, but the small sample size precluded a definitive conclusion. A large international clinical study is under way to address safety and efficacy of an S/B formulation of a pentavalent version of HRRV...

..CONCLUSIONS: QRV was generally well tolerated, immungenic, and highly effective against rotavirus gastroenteritis...

..Therefore, it is recommended that the EMcN strain be used for future challenge studies with mice on this background...

..These observations will help refine our understanding of effector and memory CD8 T cell migration patterns...

..Thus, IFN-gamma-driven obstruction of bile ducts is a key pathogenic mechanism of disease and may constitute a therapeutic target to block disease progression in patients with biliary atresia...

..Herein, we report the results from the largest prospective study in the United States determining the nonmedical costs of severe rotavirus infections...

..Thus, the rhesus model of rotavirus infection can be exploited further in studies with vaccine candidates designed to prevent or abrogate rotavirus infection...

..This unique project, which is developing a new rotavirus vaccine in India with the use of Indian strains, an Indian manufacturer, and an Indian clinical development program, aims to expedite introduction of rotavirus vaccines in India...

..Together, these results establish CD4 T cells as effectors of protection against rotavirus after intranasal immunization of mice with VP6 and LT(R192G)...

..Rotavirus is a major cause of gastroenteritis in children worldwide and is estimated to be responsible for more than 500,000 physician visits, 50,000 hospitalizations and 20 deaths in the United States each year...

..Therefore, TUCH infection of macaques provides a useful nonhuman primate model for studies on rotavirus protection...

..Thus, expression of complete rotavirus VP6 protein was greatly enhanced by codon optimization, and the protection elicited was not affected by denaturation of recombinant VP6...

..The data also suggest that chronic colitis in rhesus macaques may have potential as a model of inflammatory bowel disease in humans...

..Although rotaviruses (RVs) are the most common cause of severe gastroenteritis in children, there is a lack of information detailing the spectrum of clinical manifestations of RV disease resulting in hospitalization...