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Open Forum Infect Dis. 2015 May 14;2(2):ofv067. doi: 10.1093/ofid/ofv067. eCollection 2015 Apr.

Hemagglutination Inhibition Antibody Titers as a Correlate of Protection Against Seasonal A/H3N2 Influenza Disease.

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Institut de Statistique, Biostatistique et Sciences Actuarielles, Université Catholique de Louvain , Louvain-la-Neuve , Belgium.
Vaccination and Travel Medicine Centre , Poliklinika II , Hradec Králové , Czech Republic.
GSK Vaccines , Rixensart , Belgium.
Institut für Tropenmedizin, Universitätsklinikum Tübingen , Germany.
Université Paris Descartes, Sorbonne Paris Cité; Assistance Publique Hôpitaux de Paris, Hôpital Cochin, CIC Cochin-Pasteur; Inserm, CIC 1417-REIVAC , Paris , France.
Centre for Vaccinology , Ghent University and Hospital , Belgium.
Alan M. McGavin Chair in Geriatrics Research, Department of Medicine , University of British Columbia , Vancouver , Canada.
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&M Health Science Center College of Medicine , Temple.
Group Health Research Institute , Seattle, Washington.
Vaccine Research Center , University of Tampere , Finland.
GSK Vaccines , King of Prussia, Pennsylvania.



 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.


 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.


 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.


 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.


A/H3N2; influenza; modeling; serologic correlates; vaccine

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