Shousun C Szu1, Keith P Klugman2, Steven Hunt3. 1. National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD, USA. Electronic address: szus@mail.nih.gov. 2. Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA. 3. National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD, USA.
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. CONCLUSION: The 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.
RCT Entities:
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. CONCLUSION: The 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.
Entities:
Keywords:
Vi antibody protective threshold against typhoid fever Vi conjugate efficacy trial
Authors: Ngoc Lanh Mai; Van Bay Phan; Anh Ho Vo; Cong Thanh Tran; Feng Ying C Lin; Dolores A Bryla; Chiayung Chu; Joseph Schiloach; John B Robbins; Rachel Schneerson; Shousun C Szu Journal: N Engl J Med Date: 2003-10-02 Impact factor: 91.245
Authors: P Balmer; J North; D Baxter; E Stanford; A Melegaro; E B Kaczmarski; E Miller; R Borrow Journal: Clin Exp Immunol Date: 2003-09 Impact factor: 4.330
Authors: H Peltola; H Mäkelä; H Käyhty; H Jousimies; E Herva; K Hällström; A Sivonen; O V Renkonen; O Pettay; V Karanko; P Ahvonen; S Sarna Journal: N Engl J Med Date: 1977-09-29 Impact factor: 91.245
Authors: F Y Lin; V A Ho; H B Khiem; D D Trach; P V Bay; T C Thanh; Z Kossaczka; D A Bryla; J Shiloach; J B Robbins; R Schneerson; S C Szu Journal: N Engl J Med Date: 2001-04-26 Impact factor: 176.079
Authors: Do Gia Canh; Feng-ying Kimi Lin; Vu Dinh Thiem; Dang Duc Trach; Nguyen Dinh Trong; Nguyen Duc Mao; Steven Hunt; Rachel Schneerson; John B Robbins; Chiayung Chu; Joseph Shiloach; Dolores A Bryla; Marie-Claude Bonnet; Dominique Schulz; Shousun C Szu Journal: Infect Immun Date: 2004-11 Impact factor: 3.609