Immunogenicity of AS03-adjuvanted and non-adjuvanted trivalent inactivated influenza vaccines in elderly adults: A Phase 3, randomized trial and post-hoc correlate of protection analysis


Guillermo M. Ruiz-Palacios, Department of Infectious Diseases , Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Tlalpan, C.P. México City , México.
Geert Leroux-Roels, Centre for Vaccinology , Ghent University and Ghent University Hospital , Ghent , Belgium.
Jiri Beran, Vaccination and Travel Medicine Centre, Hradec Kralove, Czech Republic; and 2nd Faculty of Medicine , Charles University in Prague , Czech Republic.
Jeanne-Marie Devaster, Jeanne-Marie Devaster , MD, GSK Vaccines , Rixensart , Belgium.
Meral Esen, Institut für Tropenmedizin , Tübingen , Germany.
Odile Launay, Inserm, CIC 1417 and French Network of Clinical Investigation in Vaccinology (I-REIVAC), France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Cochin , CIC Cochin Pasteur, Paris , France.
Janet E. McElhaney, HSN Volunteer Association Chair in Geriatric Research , Health Sciences North Research Institute , Sudbury , ON , Canada.
Gerrit A. van Essen, Julius Center for Health Sciences and Primary Care , University Medical Center Utrecht , Utrecht , The Netherlands.
Anne Benoit, Institute of Statistics, Biostatistics and Actuarial Sciences, Université Catholique de Louvain , Louvain-la-Neuve , Belgium.
Carine Claeys, GSK Vaccines , Wavre , Belgium.
Walthère Dewé, GSK Vaccines , Rixensart , Belgium.
Christelle Durand, GSK Vaccines , Wavre , Belgium.
Xavier Duval, Hôpital Bichat Claude Bernard, GH BICHAT. Paris cedex 18, France; Inserm, CIC 007 for the French Network of Clinical Investigation in Vaccinology (REIVAC) , Paris Cedex 18, France.
Ann R. Falsey, Rochester General Hospital , Rochester , NY , USA.
Gregory Feldman, Carolina Pharmaceutical Research , Spartanburg , South Carolina , United States.
Florence Galtier, CHRU de Montpellier, Hôpital Saint Eloi, Montpellier, France; Inserm, CIC 1001 for the French Network of Clinical Investigation in Vaccinology (REIVAC) , Montpellier , France.
Pierre Gervais, Q&T Research Sherbrooke , Sherbrooke , QC , Canada.
Shinn-Jang Hwang, Department of Family Medicine , Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University School of Medicine , Taipei , Taiwan.
Shelly McNeil, Queen Elizabeth Health Sciences Centre , Dalhousie University, PCIRN, NACI, CCfV, CAIRE, QEII HSC - VG Site Infectious Diseases , Halifax, Nova Scotia , Canada.
Jan Hendrik Richardus, GGD Rotterdam-Rijnmond , Rotterdam , The Netherlands.
Andrew Trofa, GSK Vaccines , King of Prussia , PA , USA.
Lidia Oostvogels, GSK Vaccines , Wavre , Belgium.



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Human Vaccines & Immunotherapeutics


In this study we describe the immunogenicity results from a subset of older people (N = 5187) who participated in a Phase 3 randomized, observer-blinded trial of AS03-TIV versus TIV (Fluarix™) (ClinicalTrials.gov, NCT00753272). Participants received one dose of AS03-TIV or TIV in each study year and antibody titers against the vaccine strains were assessed using hemagglutination-inhibition (HI) assay at 21 d and 180 d post-vaccination in each vaccine group in the 2008/09 (Year 1) and 2009/10 (Year 2) influenza seasons. Manufacturing consistency of 3 lots of AS03-TIV for HI antibody responses in Year 1 was a co-primary objective. In a post-hoc analysis, a statistical regression model included 4830 subjects in whom immunogenicity and laboratory-confirmed attack rate data were available; the analysis was performed to assess HI antibody titers against A/H3N2 as a correlate of protection for laboratory-confirmed A/H3N2 influenza. AS03-TIV and TIV elicited strong HI antibody responses against each vaccine strain 21 d post-vaccination in both years. The manufacturing consistency of 3 lots of AS03-TIV was demonstrated. In both years and each vaccine group, HI antibody responses were lower for A/H1N1 than the other vaccine strains. Day 180 seroconversion rates (proportion with ≥4-fold increase in titer compared with pre-vaccination titer) in Year 1 in the AS03-TIV and TIV groups, respectively, were 87.7% and 74.1% for A/H3N2, 69.7% and 59.6% for influenza B, and 58.3% and 47.4% for A/H1N1. The post-hoc statistical model based on A/H3N2 attack rates and HI antibody titers estimated that a 4-fold increase in post-vaccination titers against A/H3N2 was associated with a 2-fold decrease in the odds of A/H3N2 infection.

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Medical Subject Headings

Aged; Aged, 80 and over; Antibodies, Viral (blood); Drug Combinations; Female; Hemagglutination Inhibition Tests; Humans; Influenza A Virus, H3N2 Subtype (immunology); Influenza Vaccines (administration & dosage, immunology); Influenza, Human (prevention & control, virology); Male; Polysorbates (administration & dosage); Single-Blind Method; Squalene (administration & dosage); Treatment Outcome; Vaccines, Inactivated (administration & dosage, immunology); alpha-Tocopherol (administration & dosage)

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