title: On the relationship between mean antibody level, seroprotection and clinical protection from influenza.
abstract: For many vaccines the amount of antibodies induced has a positive correlation with the likelihood of clinical protection from disease. Mean antibody level is therefore frequently used as a serological surrogate endpoint for vaccine efficacy. In addition, a dichotomous surrogate endpoint is often defined: seroprotection. We explore the relationship between mean antibody level, seroprotection and clinical protection from influenza, using a simple statistical model. The model reveals that the relationship depends not only on the mean but also on the dispersion of the antibody levels, the threshold for clinical protection and the clinical protection curve. The consequences for the interpretation of mean antibody levels and seroprotection rates in terms of clinical protection from influenza are discussed.
authors.affiliation: Global Statistics, Solvay Pharmaceuticals, P.O. Box 900, NL-1380 DA Weesp, The Netherlands. jos.nauta@solvay.com
authors.forename: Jozef J P
authors.initials: JJ
authors.lastname: Nauta
authors.forename: Walter E P
authors.initials: WE
authors.lastname: Beyer
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
mesh_terms: D000906:Antibodies / Q000032:analysis / Q000097:blood*; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D006801:Humans; D007252:Influenza Vaccines / Q000276:immunology / Q000627:therapeutic use; D007251:Influenza, Human / Q000097:blood* / Q000276:immunology / Q000517:prevention & control*; D008962:Models, Theoretical; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods
chemical_list: D000906:Antibodies; D015415:Biomarkers; D007252:Influenza Vaccines