title: Hemagglutination Inhibition Antibody Titers as a Correlate of Protection Against Seasonal A/H3N2 Influenza Disease.
abstract: Background.  To investigate the relationship between hemagglutinin-inhibition (HI) antibody levels to the risk of influenza disease, we conducted a correlate of protection analysis using pooled data from previously published randomized trials. Methods.  Data on the occurrence of laboratory-confirmed influenza and HI levels pre- and postvaccination were analyzed from 4 datasets: 3 datasets included subjects aged <65 years who received inactivated trivalent influenza vaccine (TIV) or placebo, and 1 dataset included subjects aged ≥65 years who received AS03-adjuvanted TIV (AS03-TIV) or TIV. A logistic model was used to evaluate the relationship between the postvaccination titer of A/H3N2 HI antibodies and occurrence of A/H3N2 disease. We then built a receiver-operating characteristic curve to identify a potential cutoff titer between protection and no protection. Results.  The baseline odds ratio of A/H3N2 disease was higher for subjects aged ≥65 years than <65 years and higher in seasons of strong epidemic intensity than moderate or low intensity. Including age and epidemic intensity as covariates, a 4-fold increase in titer was associated with a 2-fold decrease in the risk of A/H3N2 disease. Conclusions.  The modeling exercise confirmed a relationship between A/H3N2 disease and HI responses, but it did not allow an evaluation of the predictive power of the HI response.
authors.affiliation: Institut de Statistique, Biostatistique et Sciences Actuarielles, Université Catholique de Louvain , Louvain-la-Neuve , Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Benoit
authors.affiliation: Vaccination and Travel Medicine Centre , Poliklinika II , Hradec Králové , Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Beran
authors.affiliation: GSK Vaccines , Rixensart , Belgium.
authors.forename: Jeanne-Marie
authors.initials: JM
authors.lastname: Devaster
authors.affiliation: Institut für Tropenmedizin, Universitätsklinikum Tübingen , Germany.
authors.forename: Meral
authors.initials: M
authors.lastname: Esen
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité; Assistance Publique Hôpitaux de Paris, Hôpital Cochin, CIC Cochin-Pasteur; Inserm, CIC 1417-REIVAC , Paris , France.
authors.forename: Odile
authors.initials: O
authors.lastname: Launay
authors.affiliation: Centre for Vaccinology , Ghent University and Hospital , Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
authors.affiliation: Alan M. McGavin Chair in Geriatrics Research, Department of Medicine , University of British Columbia , Vancouver , Canada.
authors.forename: Janet E
authors.initials: JE
authors.lastname: McElhaney
authors.affiliation: GSK Vaccines , Rixensart , Belgium.
authors.forename: Lidia
authors.initials: L
authors.lastname: Oostvogels
authors.affiliation: Julius Center for Health Sciences and Primary Care , University Medical Center Utrecht , The Netherlands.
authors.forename: Gerrit A
authors.initials: GA
authors.lastname: van Essen
authors.affiliation: Section of Pediatric Infectious Diseases, Baylor Scott and White Health , Texas A&M Health Science Center College of Medicine , Temple.
authors.forename: Manjusha
authors.initials: M
authors.lastname: Gaglani
authors.affiliation: Group Health Research Institute , Seattle, Washington.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Jackson
authors.affiliation: Vaccine Research Center , University of Tampere , Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Vesikari
authors.affiliation: Institut de Statistique, Biostatistique et Sciences Actuarielles, Université Catholique de Louvain , Louvain-la-Neuve , Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Legrand
authors.affiliation: GSK Vaccines , Rixensart , Belgium.
authors.forename: Fabian
authors.initials: F
authors.lastname: Tibaldi
authors.affiliation: GSK Vaccines , King of Prussia, Pennsylvania.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Innis
authors.affiliation: GSK Vaccines , Rixensart , Belgium.
authors.forename: Walthère
authors.initials: W
authors.lastname: Dewé
keywords: A/H3N2; influenza; modeling; serologic correlates; vaccine