title: Mucosal and Cellular Immune Responses to Norwalk Virus.
abstract: BACKGROUND
  Noroviruses are a leading cause of acute gastroenteritis worldwide. Mucosal and cellular immune responses remain poorly understood, with most studies of noroviruses having focused on serological responses to infection.
  
  
  METHODS
  We used saliva, feces, and peripheral blood mononuclear cells collected from persons who were administered Norwalk virus (NV) to characterize mucosal (salivary and fecal immunoglobulin A [IgA]) and cellular (NV-specific IgA and immunoglobulin G [IgG] antibody-secreting cells and total and NV-specific IgA and IgG memory B cells) immune responses following infection.
  
  
  RESULTS
  Prechallenge levels of NV-specific salivary IgA and NV-specific memory IgG cells correlated with protection from gastroenteritis, whereas prechallenge levels of NV-specific fecal IgA correlated with a reduced viral load. Antibody-secreting cell responses were biased toward IgA, while memory B-cell responses were biased toward IgG. NV-specific memory B cells but not antibody-secreting cells persisted 180 days after infection.
  
  
  CONCLUSIONS
  NV-specific salivary IgA and NV-specific memory IgG cells were identified as new correlates of protection against NV gastroenteritis. Understanding the relative importance of mucosal, cellular, and humoral immunity is important in developing vaccine strategies for norovirus disease prevention.
authors: Department of Molecular Virology and Microbiology.
authors: Sasirekha
authors: S
authors: Ramani
authors: Department of Molecular Virology and Microbiology.
authors: Frederick H
authors: FH
authors: Neill
authors: Department of Medicine.
authors: Antone R
authors: AR
authors: Opekun
authors: Department of Pediatrics, Baylor College of Medicine, Houston Children's Hospital of San Antonio, Texas.
authors: Mark A
authors: MA
authors: Gilger
authors: Department of Molecular Virology and Microbiology Department of Medicine.
authors: David Y
authors: DY
authors: Graham
authors: Department of Molecular Virology and Microbiology Department of Medicine.
authors: Mary K
authors: MK
authors: Estes
authors: Department of Molecular Virology and Microbiology Department of Medicine.
authors: Robert L
authors: RL
authors: Atmar
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D017250:Caliciviridae Infections / Q000276:immunology* / Q000821:virology; D005243:Feces / Q000737:chemistry; D005759:Gastroenteritis / Q000276:immunology* / Q000821:virology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009663:Norwalk virus / Q000276:immunology*; D012463:Saliva / Q000737:chemistry
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G
keywords: IgA; IgG; Norovirus; Norwalk virus; antibody-secreting cells; correlate of protection; fecal IgA; immune response; memory B cells; salivary IgA
references: J Infect Dis. 1995 Mar;171(3):566-9
references: 7876602
references: J Immunol Methods. 1988 May 25;110(1):85-91
references: 3373004
references: J Med Virol. 2005 Sep;77(1):116-20
references: 16032732
references: J Virol. 2007 Jan;81(1):215-28
references: 17050593
references: J Infect Dis. 2010 Oct 15;202(8):1212-8
references: 20815703
references: J Infect Dis. 2010 Dec 1;202(11):1649-58
references: 20979455
references: Clin Vaccine Immunol. 2011 Jul;18(7):1187-90
references: 21593238
references: N Engl J Med. 2011 Dec 8;365(23):2178-87
references: 22150036
references: Clin Immunol. 2012 Aug;144(2):98-108
references: 22710446
references: Clin Vaccine Immunol. 2012 Jun;19(6):842-8
references: 22518009
references: Clin Infect Dis. 2012 Jun;54(11):1615-7
references: 22437237
references: Clin Vaccine Immunol. 2012 Dec;19(12):1980-3
references: 23035177
references: Emerg Infect Dis. 2013 Aug;19(8):1198-205
references: 23876403
references: Emerg Infect Dis. 2013 Aug;19(8):1260-7
references: 23876612
references: Curr Opin Gastroenterol. 2014 Jan;30(1):25-33
references: 24232370
references: J Infect Dis. 2014 Apr 1;209(7):1016-22
references: 24253285
references: Lancet Infect Dis. 2014 Aug;14(8):725-30
references: 24981041
references: J Infect Dis. 2014 Dec 1;210(11):1763-71
references: 24951828
references: Infect Immun. 2000 May;68(5):2692-7
references: 10768961
references: Nat Med. 2003 May;9(5):548-53
references: 12692541
references: J Immunol Methods. 2004 Mar;286(1-2):111-22
references: 15087226
references: J Virol. 2005 Mar;79(5):2900-9
references: 15709009