Susceptibility and Protective Immunity to Noroviruses

Summary

Principal Investigator: Ralph Baric
Affiliation: University of North Carolina
Country: USA
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

Top Publications

  1. ncbi Cellular and humoral immunity following Snow Mountain virus challenge
    Lisa Lindesmith
    School of Public Health, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA
    J Virol 79:2900-9. 2005
  2. ncbi Multivalent norovirus vaccines induce strong mucosal and systemic blocking antibodies against multiple strains
    Anna 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
  3. ncbi Mechanisms of GII.4 norovirus persistence in human populations
    Lisa C Lindesmith
    University of North Carolina Chapel Hill, Chapel Hill, North Carolina, USA
    PLoS Med 5:e31. 2008
  4. ncbi Herd immunity to GII.4 noroviruses is supported by outbreak patient sera
    Jennifer L Cannon
    Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA
    J Virol 83:5363-74. 2009
  5. ncbi Heterotypic humoral and cellular immune responses following Norwalk virus infection
    Lisa C Lindesmith
    Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Virol 84:1800-15. 2010

Scientific Experts

  • Jennifer L Cannon
  • Ralph Baric
  • Lisa C Lindesmith
  • Anna D LoBue
  • Lisa Lindesmith
  • Robert E Johnston
  • Christine L Moe
  • Jeffrey A Frelinger
  • Juan Leon
  • David J Weber
  • Eric Donaldson
  • Du-Ping Zheng
  • Du Ping Zheng
  • Eric F Donaldson
  • Jan Vinje
  • Patrick R Harrington
  • Boyd Yount
  • Joseph M Thompson
  • John Treanor
  • Jacques Lependu
  • Christine Moe

Detail Information

Publications5

  1. ncbi Cellular and humoral immunity following Snow Mountain virus challenge
    Lisa 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...
  2. ncbi Multivalent norovirus vaccines induce strong mucosal and systemic blocking antibodies against multiple strains
    Anna 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...
  3. ncbi Mechanisms of GII.4 norovirus persistence in human populations
    Lisa 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...
  4. ncbi Herd immunity to GII.4 noroviruses is supported by outbreak patient sera
    Jennifer 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...
  5. ncbi Heterotypic humoral and cellular immune responses following Norwalk virus infection
    Lisa 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...