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OBJECTIVES: Establishing a correlate of protection is essential for the development and licensure of Shigella vaccines. We examined potential threshold levels of serum IgG to Shigella lipopolysaccharide (LPS) that could predict protection against shigellosis. METHODS: We performed new analyses of serologic and vaccine efficacy (VE) data from 2 randomized vaccine-controlled trials of the S. sonnei-rEPA conjugate conducted in young adults and children aged 1-4 years in Israel. Adults received either S. sonnei-rEPA (N=183) or control vaccines (N=277). Children received the S. sonnei-rEPA conjugate (N=1384) or S. flexneri 2a-rEPA conjugate (N=1315). VE against culture-proven shigellosis was determined. Sera were tested for IgG anti-S. sonnei LPS antibodies. We assessed the association of various levels of IgG anti-S. sonnei LPS antibodies with S. sonnei shigellosis risk using logistic regression models and reverse cumulative distribution of IgG levels. RESULTS: Among adults, 4 vaccinees and 23 controls developed S. sonnei shigellosis; VE 74% (95% CI 28-100). A threshold of >1:1600 IgG anti-S. sonnei LPS titer was associated with a reduced risk of S. sonnei shigellosis and predicted VE of 73.6% (95% CI 65-80). The IgG anti-S. sonnei LPS correlated with serum bactericidal titers. In children, a population-based level of 4.5 EU (corresponding to 1:1072 titer) predicted VE of 63%, versus 71% observed VE in the 3-4 year-olds. The predicted VE in 2-4 year-olds was 49%, consistent with the 52% observed VE. CONCLUSION: Serum IgG anti-S. sonnei LPS threshold levels can predict degrees of vaccine efficacy and be used for the evaluation of new vaccine candidates.

Original publication




Journal article


Clin Microbiol Infect

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