Serial Vaccination and the Antigenic Distance Hypothesis: Effects on Influenza Vaccine Effectiveness During A(H3N2) Epidemics in Canada, 2010-2011 to 2014-2015.
The antigenic distance hypothesis (ADH) predicts that negative interference from prior season's influenza vaccine (v1) on the current season's vaccine (v2) protection may occur when the antigenic distance is small between v1 and v2 (v1 ≈ v2) but large between v1 and the current epidemic (e) strain (v1 ≠ e).



Vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza A(H3N2) illness was estimated by test-negative design during 3 A(H3N2) epidemics (2010-2011, 2012-2013, 2014-2015) in Canada. Vaccine effectiveness was derived with covariate adjustment across v2 and/or v1 categories relative to no vaccine receipt among outpatients aged ≥9 years. Prior vaccination effects were interpreted within the ADH framework.



Prior vaccination effects varied significantly by season, consistent with the ADH. There was no interference by v1 in 2010-2011 when v1 ≠ v2 and v1 ≠ e, with comparable VE for v2 alone or v2 + v1: 34% (95% confidence interval [CI] = -51% to 71%) versus 34% (95% CI = -5% to 58%). Negative interference by v1 was suggested in 2012-2013 with nonsignificant reduction in VE when v1 ≈ v2 and v1 ≠ e: 49% (95% CI = -47% to 83%) versus 28% (95% CI = -12% to 54%). Negative effects of prior vaccination were pronounced and statistically significant in 2014-2015 when v1 ≡ v2 and v1 ≠ e: 65% (95% CI = 25% to 83%) versus -33% (95% CI = -78% to 1%).



Effects of repeat influenza vaccination were consistent with the ADH and may have contributed to findings of low VE across recent A(H3N2) epidemics since 2010 in Canada.
Communicable Disease Prevention and Control Services, British Columbia Centre for Disease Control, Vancouver.|School of Population and Public Health, University of British Columbia, Vancouver.
Danuta M
DM
Skowronski
Communicable Disease Prevention and Control Services, British Columbia Centre for Disease Control, Vancouver.
Catharine
C
Chambers
Direction of Biological and Occupational Risks, Institut national de santé publique du Québec.|Department of Social and Preventive Medicine, Laval University, Québec.|Infection and Immunity, Centre Hospitalier Universitaire de Québec Research Centre.
Gaston
G
De Serres
British Columbia Centre for Disease Control Public Health Laboratory, Vancouver.
Suzana
S
Sabaiduc
Communicable Diseases, Emergency Preparedness and Response, Public Health Ontario, Toronto.
Anne-Luise
AL
Winter
Departments of Family Medicine and Community Health Sciences, University of Calgary.
James A
JA
Dickinson
Public Health Ontario Laboratory, Public Health Ontario, Toronto.|Departments of Laboratory Medicine and Pathobiology and Paediatrics, University of Toronto.
Jonathan B
JB
Gubbay
Diagnostic Virology, Alberta Provincial Laboratory, Calgary.|Department of Microbiology, Immunology and Infectious Diseases, University of Calgary.
Kevin
K
Fonseca
Diagnostic Virology, Alberta Provincial Laboratory, Edmonton.|Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton.
Steven J
SJ
Drews
Laboratoire de santé publique du Québec, Institut national de santé publique du Québec.|Département de microbiologie, d'infectiologie et d'immunologie, l'Université de Montréal.
Hugues
H
Charest
Laboratoire de santé publique du Québec, Institut national de santé publique du Québec.
Christine
C
Martineau
British Columbia Centre for Disease Control Public Health Laboratory, Vancouver.|Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver.
Mel
M
Krajden
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver.
Martin
M
Petric
Infectious Disease Prevention and Control Branch, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada; and.
Nathalie
N
Bastien
Infectious Disease Prevention and Control Branch, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada; and.
Yan
Y
Li
Department of Zoology, University of Cambridge, England.
Derek J
DJ
Smith
D000293:Adolescent; D000328:Adult; D000368:Aged; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D002648:Child; D058872:Epidemics / Q000517:prevention & control*; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype; D007252:Influenza Vaccines / Q000276:immunology / Q000627:therapeutic use*; D007251:Influenza, Human / Q000453:epidemiology / Q000517:prevention & control*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012621:Seasons; D018571:Sentinel Surveillance; D014611:Vaccination / Q000706:statistics & numerical data*; D055815:Young Adult
D007252:Influenza Vaccines
antigenic distance hypothesis; antigenic site.; genomic sequencing; hemagglutination inhibition; influenza; influenza A(H3N2) subtype; influenza vaccine; negative interference; repeat vaccination; vaccine effectiveness