A framework for assessing immunological correlates of protection in vaccine trials.
A central goal of vaccine research is to identify a vaccine-induced immune response that predicts protection from infection or disease. The term "correlate of protection" has been used to refer to at least 3 distinct concepts, which has resulted in confusion surrounding this topic. We propose precise definitions of these different concepts of immune correlates, using the nomenclature "correlate of risk," "level 1 surrogate of protection," and "level 2 surrogate of protection." We suggest a general framework for assessing these 3 levels of immune correlates in vaccine efficacy trials. To demonstrate the proposed principles, we analyze data from a 1943 influenza vaccine field trial, supporting Weiss strain A-specific antibody titers as a level 1 surrogate of protection. Other real and simulated examples are also discussed.
Qin
Li
L
Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. lqin@scharp.org
Gilbert
Peter B
PB
Corey
Lawrence
L
McElrath
M Juliana
MJ
Self
Steven G
SG
D000906:Antibodies / Q000097:blood; D000917:Antibody Formation; D015415:Biomarkers; D002986:Clinical Trials as Topic; D006801:Humans; D007114:Immunization; D014612:Vaccines / Q000276:immunology*
D000906:Antibodies; D015415:Biomarkers; D014612:Vaccines