title: Lack of homologous protection against Campylobacter jejuni CG8421 in a human challenge model.
abstract: BACKGROUND
  Campylobacter jejuni is a common cause of diarrhea and is associated with serious postinfectious sequelae. Although symptomatic and asymptomatic infections are recognized, protective immunity is not well understood. Previous data suggests that interferon γ (IFN-γ) may be associated with protection. To better define the clinical and immunologic development of protective immunity to C. jejuni, we assessed the ability of an initial infection to prevent clinical illness after a second experimental infection.
  
  
  METHODS
  Subjects with no clinical or immunologic evidence of prior infection with C. jejuni received an initial challenge with C. jejuni CG8421 with rechallenge 3 months later. The primary endpoint was campylobacteriosis, as defined by diarrhea and/or systemic signs. Close inpatient monitoring was performed. Serum immunoglobulin A (IgA) and immunoglobulin G (IgG), fecal IgA, IgA antibody-secreting cells (ASCs), and IFN-γ production were evaluated. All subjects were treated with antibiotics and were clinically well at discharge.
  
  
  RESULTS
  Fifteen subjects underwent a primary infection with C. jejuni CG8421; 14 (93.3%) experienced campylobacteriosis. Eight subjects received the second challenge, and all experienced campylobacteriosis with similar severity. Immune responses after primary infection included serum IgA, IgG, ASC, and IFN-γ production. Responses were less robust after secondary infection.
  
  
  CONCLUSIONS
  In naive healthy adults, a single infection with CG8421 did not protect against campylobacteriosis. Although protection has been demonstrated with other strains and after continuous environmental exposure, our work highlights the importance of prior immunity, repeated exposures, and strain differences in protective immunity to C. jejuni.
  
  
  BACKGROUND
  NCT01048112.
authors.affiliation: University of Vermont College of Medicine, Unit of Infectious Diseases and Vaccine Testing Center, Burlington, Vermont.
authors.forename: Beth D
authors.initials: BD
authors.lastname: Kirkpatrick
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Lyon
authors.forename: Chad K
authors.initials: CK
authors.lastname: Porter
authors.forename: Alex C
authors.initials: AC
authors.lastname: Maue
authors.forename: Patricia
authors.initials: P
authors.lastname: Guerry
authors.forename: Kristen K
authors.initials: KK
authors.lastname: Pierce
authors.forename: Marya P
authors.initials: MP
authors.lastname: Carmolli
authors.forename: Mark S
authors.initials: MS
authors.lastname: Riddle
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Larsson
authors.forename: Douglas
authors.initials: D
authors.lastname: Hawk
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Dill
authors.forename: A
authors.initials: A
authors.lastname: Fingar
authors.forename: Frederic
authors.initials: F
authors.lastname: Poly
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Fimlaid
authors.forename: Fahmida
authors.initials: F
authors.lastname: Hoq
authors.forename: David R
authors.initials: DR
authors.lastname: Tribble
mesh_terms: D000328:Adult; D002169:Campylobacter Infections / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D016123:Campylobacter jejuni / Q000276:immunology*; D003967:Diarrhea / Q000276:immunology / Q000382:microbiology; D005243:Feces / Q000737:chemistry; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000097:blood; D008297:Male; D055815:Young Adult
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007371:Interferon-gamma
keywords: Campylobacter jejuni; Campylobacterosis; homologous protection; human challenge model