title: Vaccine-induced mucosal immunity to poliovirus: analysis of cohorts from an open-label, randomised controlled trial in Latin American infants.
abstract: BACKGROUND
  Identification of mechanisms that limit poliovirus replication is crucial for informing decisions aimed at global polio eradication. Studies of mucosal immunity induced by oral poliovirus (OPV) or inactivated poliovirus (IPV) vaccines and mixed schedules thereof will determine the effectiveness of different vaccine strategies to block virus shedding. We used samples from a clinical trial of different vaccination schedules to measure intestinal immunity as judged by neutralisation of virus and virus-specific IgA in stools.
  
  
  METHODS
  In the FIDEC trial, Latin American infants were randomly assigned to nine groups to assess the efficacy of two schedules of bivalent OPV (bOPV) and IPV and challenge with monovalent type 2 OPV, and stools samples were collected. We selected three groups of particular interest-the bOPV control group (serotypes 1 and 3 at 6, 10, and 14 weeks), the trivalent attenuated OPV (tOPV) control group (tOPV at 6, 10, and 14 weeks), and the bOPV-IPV group (bOPV at 6, 10, and 14 weeks plus IPV at 14 weeks). Neutralising activity and poliovirus type-specific IgA were measured in stool after a monovalent OPV type 2 challenge at 18 weeks of age. Mucosal immunity was measured by in-vitro neutralisation of a type 2 polio pseudovirus (PV2). Neutralisation titres and total and poliovirus-type-specific IgG and IgA concentrations in stools were assessed in samples collected before challenge and 2 weeks after challenge from all participants.
  
  
  RESULTS
  210 infants from Guatemala and Dominican Republic were included in this analysis. Of 38 infants tested for mucosal antibody in the tOPV group, two were shedding virus 1 week after challenge, compared with 59 of 85 infants receiving bOPV (p<0·0001) and 53 of 87 infants receiving bOPV-IPV (p<0·0001). Mucosal type 2 neutralisation and type-specific IgA were noted primarily in response to tOPV. An inverse correlation was noted between virus shedding and both serum type 2 neutralisation at challenge (p<0·0001) and mucosal type 2 neutralisation at challenge (p<0·0001).
  
  
  CONCLUSIONS
  Mucosal type-2-specific antibodies can be measured in stool and develop in response to receipt of OPV type 2 either in the primary vaccine series or at challenge. These mucosal antibodies influence the amount of virus that is shed in an established infection.
  
  
  BACKGROUND
  Bill & Melinda Gates Foundation.
authors.affiliation: Department of Pediatrics, Dartmouth College, Hanover, NH, USA. Electronic address: peter.f.wright@dartmouth.edu.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Wright
authors.affiliation: Department of Microbiology and Immunology, Dartmouth College, Hanover, NH, USA.
authors.forename: Ruth I
authors.initials: RI
authors.lastname: Connor
authors.affiliation: Department of Pediatrics, Dartmouth College, Hanover, NH, USA.
authors.forename: Wendy F
authors.initials: WF
authors.lastname: Wieland-Alter
authors.affiliation: Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA.
authors.forename: Anne G
authors.initials: AG
authors.lastname: Hoen
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, NH, USA.
authors.forename: Austin W
authors.initials: AW
authors.lastname: Boesch
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, NH, USA.
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Ackerman
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: M Steven
authors.initials: MS
authors.lastname: Oberste
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Gast
authors.affiliation: Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Hanover, NH, USA.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Brickley
authors.affiliation: Departments of Pediatrics and Epidemiology, University of Colorado Denver School of Medicine, Aurora, CO, USA.
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Asturias
authors.affiliation: Fighting Infectious Diseases in Emerging Countries (FIDEC), Miami, FL, USA.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Rüttimann
authors.affiliation: Bill & Melinda Gates Foundation, Seattle, WA, USA.
authors.forename: Ananda S
authors.initials: AS
authors.lastname: Bandyopadhyay
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D005243:Feces / Q000821:virology; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D007115:Immunization Schedule; D007843:Latin America; D011051:Poliomyelitis / Q000276:immunology / Q000517:prevention & control*; D017955:Poliovirus / Q000276:immunology* / Q000302:isolation & purification; D023321:Poliovirus Vaccines / Q000276:immunology*; D065288:Serogroup; D014611:Vaccination; D017201:Virus Shedding / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D023321:Poliovirus Vaccines