title: Re-examination of immune response and estimation of anti-Vi IgG protective threshold against typhoid fever-based on the efficacy trial of Vi conjugate in young children.
abstract: BACKGROUND
  The capsular polysaccharide of Salmonella enterica serovar Typhi, Vi antigen, is an essential virulence factor and a protective antigen. Similar to other polysaccharide vaccines, the protective action of Vi, both to the polysaccharide alone or when presented as a conjugate, is mediated by serum IgG Vi antibodies. The evaluation of Vi capsular polysaccharide based vaccines to prevent typhoid fever would be significantly facilitated by the identification of a "protective level" of serum antibodies to Vi antigen.
  
  
  METHODS
  The protective level of anti-Vi IgG against typhoid fever was derived from the protective efficacy and immune response of a Vi-rEPA conjugate vaccine efficacy trial. The estimation was derived by two methods: correlation of the percent efficacy and the antibody distribution profile in the vaccine group at a given period of observation, and use of the relative ratio of anti-Vi IgG levels between the vaccine and placebo groups greater or equal to the Relative Risk of typhoid fever used in the efficacy determination.
  
  
  RESULTS
  Both methods predicted a similar range of a minimum protective level of anti-Vi IgG between 1.4 and 2.0μg/ml (short term threshold). When applying a protective threshold of 10μg/ml at 6 months post immunization, an IgG level in excess of 1.4μg/ml was achieved by 90% of children at 46 months post immunization, consistent with an 89% level of protection over the duration of the study. We thus suggest that the proportion of children with Vi IgG>10μg/ml (long term threshold) 6 months after immunization may reflect the proportion protected over at least a 4 year period.
  
  
  CONCLUSIONS
  The current assignment of an anti-Vi IgG protective level may be of value when evaluating vaccine performance of future Vi conjugate vaccines.
authors.affiliation: National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD, USA. Electronic address: szus@mail.nih.gov.
authors.forename: Shousun C
authors.initials: SC
authors.lastname: Szu
authors.affiliation: Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
authors.forename: Keith P
authors.initials: KP
authors.lastname: Klugman
authors.affiliation: National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Hunt
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood*; D000917:Antibody Formation; D002675:Child, Preschool; D004311:Double-Blind Method; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D012485:Salmonella typhi; D014435:Typhoid Fever / Q000517:prevention & control*; D014436:Typhoid-Paratyphoid Vaccines / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology; D014744:Vietnam
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D011135:Polysaccharides, Bacterial; D014436:Typhoid-Paratyphoid Vaccines; D018074:Vaccines, Conjugate; C054154:capsular polysaccharide, Salmonella
keywords: Vi antibody protective threshold against typhoid fever Vi conjugate efficacy trial