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.

Alan M McGavin Chair in Geriatrics Research Department of Medicine University of British Columbia Vancouver Canada

Centre for Vaccinology Ghent University and Hospital Belgium

Group Health Research Institute Seattle Washington

GSK Vaccines King of Prussia Pennsylvania

GSK Vaccines Rixensart Belgium

Institut de Statistique Biostatistique et Sciences Actuarielles Université Catholique de Louvain Louvain la Neuve Belgium

Institut für Tropenmedizin Universitätsklinikum Tübingen Germany

Julius Center for Health Sciences and Primary Care University Medical Center Utrecht The Netherlands

Section of Pediatric Infectious Diseases Baylor Scott and White Health Texas A and M Health Science Center College of Medicine Temple

Université Paris Descartes Sorbonne Paris Cité; Assistance Publique Hôpitaux de Paris Hôpital Cochin CIC Cochin Pasteur; Inserm CIC 1417 REIVAC Paris France

Vaccination and Travel Medicine Centre Poliklinika 2 Hradec Králové Czech Republic

Vaccine Research Center University of Tampere Finland

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