Distinguishing Causation From Correlation in the Use of Correlates of Protection to Evaluate and Develop Influenza Vaccines.

Wey Wen Lim, Nancy H L Leung, Sheena G Sullivan, Eric J Tchetgen Tchetgen, Benjamin J Cowling

American journal of epidemiology 2020 Mar 02

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There is increasing attention to the need to identify new immune markers for the evaluation of existing and new influenza vaccines. Immune markers that could predict individual protection against infection and disease, commonly called correlates of protection (CoPs), play an important role in vaccine development and licensing. Here, we discuss the epidemiologic considerations when evaluating immune markers as potential CoPs for influenza vaccines and emphasize the distinction between correlation and causation. While an immune marker that correlates well with protection from infection can be used as a predictor of vaccine efficacy, it should be distinguished from an immune marker that plays a mechanistic role in conferring protection against a clinical endpoint-the latter might be a more reliable predictor of vaccine efficacy and a more appropriate target for rational vaccine design. To clearly distinguish mechanistic and nonmechanistic CoPs, we suggest using the term "correlates of protection" for nonmechanistic CoPs, and ''mediators of protection'' for mechanistic CoPs. Furthermore, because the interactions among and relative importance of correlates or mediators of protection can vary according to age or prior vaccine experience, the effect sizes and thresholds for protective effects for CoPs could also vary in different segments of the population. © The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Citation

Wey Wen Lim, Nancy H L Leung, Sheena G Sullivan, Eric J Tchetgen Tchetgen, Benjamin J Cowling. Distinguishing Causation From Correlation in the Use of Correlates of Protection to Evaluate and Develop Influenza Vaccines. American journal of epidemiology. 2020 Mar 02;189(3):185-192