Threshold Methods for Immunological Correlates of Protection

• Activity Number: 474
• Type: Contributed
• Date/Time: Wednesday, August 3, 2011 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Andrew Dunning and Xuan Chen and Huiling Xiong*+ and Fabrice Bailleux and Li Qin and Kamal Desai
• Companies: Sanofi Pasteur and Sanofi-Pasteur and Sanofi-Pasteur and Fred Hutchinson Cancer Research Center and University of London
• Keywords: vaccine ; correlate of protection ; correlate of immunity ; protective threshold ; immunological assay

Abstract

Immunological correlates of protection, here we refer to the immunological responses which are associated with protection from disease, play a central role in vaccines research. Although in reality the relationship is likely continuous: increasing assay values corresponding to increased protection from disease, in practice the use of threshold protective levels is ubiquitous. Yet limited quantitative methods exist for inferring protective thresholds from data on immunological assay values and subsequent disease occurrence. Standard methods are often unsuitable, since in most study designs a large number of unprotected subjects do not develop disease, in addition to those protected. This research examines nine threshold models and methods in terms of their suitability for estimating threshold immunological correlates of protection, and develops tests and measures of discrimination and goodness-of-fit for evaluating thresholds so found. Results are illustrated using fifteen datasets.