Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

ObjectivesEstablishing 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.MethodsWe 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.ResultsAmong 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.ConclusionSerum 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

DOI

10.1016/j.cmi.2022.10.011

Type

Journal article

Journal

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

Publication Date

12/10/2022

Addresses

Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel. Electronic address: dancohen@tauex.tau.ac.il.