• Shousun C Szu, Keith P Klugman, and Steven Hunt.
• National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD, USA. Electronic address: szus@mail.nih.gov.
• Vaccine. 2014 Apr 25; 32 (20): 2359-63.

BackgroundThe 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.MethodsThe 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.ResultsBoth 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.ConclusionThe current assignment of an anti-Vi IgG protective level may be of value when evaluating vaccine performance of future Vi conjugate vaccines.Published by Elsevier Ltd.

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