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 Regional HealthFollow
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.

Department

Medicine

Document Type

Article

Publication Title

Human Vaccines & Immunotherapeutics

Abstract

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.

First Page

3043

Last Page

3055

DOI

10.1080/21645515.2016.1219809

Volume

12

Issue

12

Publication Date

12-1-2016

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)

PubMed ID

27690762

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