title: Phase I clinical trial of O-acetylated pectin conjugate, a plant polysaccharide based typhoid vaccine.
abstract: BACKGROUND
  Typhoid fever remains an important cause of morbidity and mortality in the developing countries. Vi capsular polysaccharide conjugate vaccine demonstrated safety and efficacy in young children in high endemic regions. A novel typhoid conjugate vaccine based on plant polysaccharide pectin was studied in a phase I trial.
  
  
  METHODS
  Fruit pectin, having the same carbohydrate backbone structure as Vi, was purified from citrus peel and used as the polysaccharide source to prepare a semi-synthetic typhoid conjugate vaccine. Pectin was chemically O-acetylated (OAcPec) to antigenically resemble Vi and conjugated to carrier protein rEPA, a recombinant exoprotein A from Pseudomonas aeruginosa. 25 healthy volunteers, 18-45 years old, were injected once with OAcPec-rEPA. Safety and IgG antibodies reactive with Vi and pectin were analyzed.
  
  
  RESULTS
  No vaccine associated serious adverse reaction was reported. Six weeks after the injection of OAcPec-rEPA, 64% of the volunteers elicited >4-fold rise of anti-Vi IgG. At 26 weeks the level declined, but the difference between the levels at 6 and 26 weeks are not statistically significant. There is a direct correlation between the level of anti-Vi IgG before and after the injection (R(2)=0.96). The anti-Vi IgG can be absorbed by Vi, but not by pectin. There was no corresponding increase of anti-pectin after the injection, indicating the antibody response to OAcPec-rEPA was specific to Vi. There is no Vi-rEPA data in US adults for comparison of immune responses. The OAcPec-rEPA elicited significantly less IgG anti-Vi in US adults than those by Vi-rEPA in Vietnamese adults.
  
  
  CONCLUSIONS
  The O-acetylated pectin conjugate, a plant based typhoid vaccine, is safe and immunogenic in adult volunteers. ClinicalTrial.gov identifier: NCT00277147, NIH Protocol ID number: OH06-CH-0070, FDA BB Investigation New Drug (IND) number 6989.
authors.affiliation: Eunice Kennedy Shriver, National Institute of Child Health & Human Development, National Institutes of Health, USA. Electronic address: Szus@mail.nih.gov.
authors.forename: Shousun C
authors.initials: SC
authors.lastname: Szu
authors.affiliation: Eunice Kennedy Shriver, National Institute of Child Health & Human Development, National Institutes of Health, USA.
authors.forename: Kimi F-Y
authors.initials: KF
authors.lastname: Lin
authors.affiliation: Eunice Kennedy Shriver, National Institute of Child Health & Human Development, National Institutes of Health, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Hunt
authors.affiliation: Eunice Kennedy Shriver, National Institute of Child Health & Human Development, National Institutes of Health, USA.
authors.forename: Chiayung
authors.initials: C
authors.lastname: Chu
authors.affiliation: Division of Food Safety, Department of Agriculture, Ho Chi Ming City, Viet Nam.
authors.forename: Nguyen Duc
authors.initials: ND
authors.lastname: Thinh
mesh_terms: D000107:Acetylation; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D002957:Citrus / Q000737:chemistry; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D010368:Pectins / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000276:immunology; D014435:Typhoid Fever / Q000517:prevention & control*; D014436:Typhoid-Paratyphoid Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D018074:Vaccines, Conjugate / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D011135:Polysaccharides, Bacterial; D011994:Recombinant Proteins; D014436:Typhoid-Paratyphoid Vaccines; D018074:Vaccines, Conjugate; C057664:Vi polysaccharide vaccine, typhoid; D010368:Pectins
keywords: Phase I pectin-based; Plant polysaccharide; Safety immunogenicity; Semi-synthetic; Typhoid conjugate vaccine