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.
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.
a Department of Infectious Diseases , Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Tlalpan, C.P. México City , México.
Guillermo M
GM
Ruiz-Palacios
b Centre for Vaccinology , Ghent University and Ghent University Hospital , Ghent , Belgium.
Geert
G
Leroux-Roels
c Vaccination and Travel Medicine Centre, Hradec Kralove, Czech Republic; and 2nd Faculty of Medicine , Charles University in Prague , Czech Republic.
Jiri
J
Beran
d Jeanne-Marie Devaster , MD, GSK Vaccines , Rixensart , Belgium.
Jeanne-Marie
JM
Devaster
e Institut für Tropenmedizin , Tübingen , Germany.
Meral
M
Esen
f 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.
Odile
O
Launay
g HSN Volunteer Association Chair in Geriatric Research , Health Sciences North Research Institute , Sudbury , ON , Canada.
Janet E
JE
McElhaney
h Julius Center for Health Sciences and Primary Care , University Medical Center Utrecht , Utrecht , The Netherlands.
Gerrit A
GA
van Essen
i Institute of Statistics, Biostatistics and Actuarial Sciences, Université Catholique de Louvain , Louvain-la-Neuve , Belgium.
Anne
A
Benoit
j GSK Vaccines , Wavre , Belgium.
Carine
C
Claeys
k GSK Vaccines , Rixensart , Belgium.
Walthère
W
Dewé
l GSK Vaccines , Wavre , Belgium.
Christelle
C
Durand
m 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.
Xavier
X
Duval
n University of Rochester Medical Center , Rochester General Hospital , Rochester , NY , USA.
Ann R
AR
Falsey
o Carolina Pharmaceutical Research , Spartanburg , South Carolina , United States.
Gregory
G
Feldman
p CHRU de Montpellier, Hôpital Saint Eloi, Montpellier, France; Inserm, CIC 1001 for the French Network of Clinical Investigation in Vaccinology (REIVAC) , Montpellier , France.
Florence
F
Galtier
q Q&T Research Sherbrooke , Sherbrooke , QC , Canada.
Pierre
P
Gervais
r Department of Family Medicine , Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University School of Medicine , Taipei , Taiwan.
Shinn-Jang
SJ
Hwang
s Queen Elizabeth Health Sciences Centre , Dalhousie University, PCIRN, NACI, CCfV, CAIRE, QEII HSC - VG Site Infectious Diseases , Halifax, Nova Scotia , Canada.
Shelly
S
McNeil
t GGD Rotterdam-Rijnmond , Rotterdam , The Netherlands.
Jan Hendrik
JH
Richardus
u GSK Vaccines , King of Prussia , PA , USA.
Andrew
A
Trofa
v GSK Vaccines , Wavre , Belgium.
Lidia
L
Oostvogels
D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D004338:Drug Combinations; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control* / Q000821:virology; D008297:Male; D011136:Polysorbates / Q000008:administration & dosage*; D016037:Single-Blind Method; D013185:Squalene / Q000008:administration & dosage*; D016896:Treatment Outcome; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D024502:alpha-Tocopherol / Q000008:administration & dosage*
D000914:Antibodies, Viral; D004338:Drug Combinations; D007252:Influenza Vaccines; D011136:Polysorbates; D015164:Vaccines, Inactivated; D013185:Squalene; C550253:AS03 adjuvant; D024502:alpha-Tocopherol
AS03; correlates of protection; immunogenicity; older; seasonal influenza; vaccine
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