Susceptibility and Protective Immunity to Noroviruses
Principal Investigator: Ralph Baric
Affiliation: University of North Carolina
Abstract: Norwalk-like viruses (NLV), a genus within the Caliciviridae, are the major cause of epidemic gastroenteritis in the US and a significant cause of severe diarrhea in young children. Based on their low infectious dose, high transmissibility and economic impact, NLVs have been classified as Bioterrorism Category B Priority Pathogens by the U.S. Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases. The long-term goals of this proposal are to elucidate the molecular mechanisms governing human susceptibility to NLV infection. In this capacity, we will use human challenge models to test various hypotheses that specific human susceptibility alleles and acquired immune factors determine NLV infection outcomes and pathogenicity. It is anticipated that the identification of host factors and responses that influence NLV pathogenesis will reveal fundamental insights into the molecular biology of these viruses, simultaneously allowing for the development of NLV vaccine and therapeutic strategies. A second goal is to develop NLV vaccines using alphaviruses as heterologous vaccine vectors. Venezuelan equine encephalitis virus (VEE)-based vaccines elicit high levels of mucosal and systemic immunity against NLVs. We will test various hypotheses that VEE replicon particles (VRPs) encoding different genogroup I and II (GI and GII) NLV capsid genes elicit strong systemic, cellular and mucosal immune responses against homologous and heterologous NLVs and are superior to the current standards for NLV vaccine development (NLV recombinant virus-like particles (VLPs) and edible vaccines).
Funding Period: 2003-07-01 - 2007-12-31
more information: NIH RePORT
- Cellular and humoral immunity following Snow Mountain virus challengeLisa Lindesmith
School of Public Health, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA
J Virol 79:2900-9. 2005..To our knowledge, this is the first report characterizing T-cell and cytokine responses following live norovirus challenge...
- Multivalent norovirus vaccines induce strong mucosal and systemic blocking antibodies against multiple strainsAnna D LoBue
Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7435, United States
Vaccine 24:5220-34. 2006..These data suggest that multivalent vaccination may provide better protection from a broader range of noroviruses than monovalent vaccination...
- Mechanisms of GII.4 norovirus persistence in human populationsLisa C Lindesmith
University of North Carolina Chapel Hill, Chapel Hill, North Carolina, USA
PLoS Med 5:e31. 2008..4 strains is common in human populations. In this article, we analyze molecular mechanisms governing GII.4 epidemiology, susceptibility, and persistence in human populations...
- Herd immunity to GII.4 noroviruses is supported by outbreak patient seraJennifer L Cannon
Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA
J Virol 83:5363-74. 2009..4 NoV. These results support the hypothesis that herd immunity is a driving force for GII.4 evolution in the U.S. population. The data also suggest that complex patterns of cross-protection may exist across NoV genotypes in humans...
- Heterotypic humoral and cellular immune responses following Norwalk virus infectionLisa C Lindesmith
Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
J Virol 84:1800-15. 2010..1-1968-challenged individuals and highlight a potential complication in the design of efficacious norovirus vaccines...