title: A framework for assessing immunological correlates of protection in vaccine trials.
abstract: 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.
authors.affiliation: Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. lqin@scharp.org
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.forename: Peter B
authors.initials: PB
authors.lastname: Gilbert
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: Steven G
authors.initials: SG
authors.lastname: Self
mesh_terms: D000906:Antibodies / Q000097:blood; D000917:Antibody Formation; D015415:Biomarkers; D002986:Clinical Trials as Topic; D006801:Humans; D007114:Immunization; D014612:Vaccines / Q000276:immunology*
chemical_list: D000906:Antibodies; D015415:Biomarkers; D014612:Vaccines