Rapid communication Open Access
Like 0


Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network (SPSN) assessed interim 2016/17 influenza vaccine effectiveness (VE) against dominant influenza A(H3N2) viruses considered antigenically matched to the clade 3C.2a vaccine strain. Sequence analysis revealed substantial heterogeneity in emerging 3C.2a1 variants by province and over time. Adjusted VE was 42% (95% confidence interval: 18–59%) overall, with variation by province. Interim virological and VE findings reported here warrant further investigation to inform potential vaccine reformulation.


Article metrics loading...

Loading full text...

Full text loading...



  1. Public Health Agency of Canada (PHAC). FluWatch report: January 8 to January 14, 2017 (week 2). Ottawa: PHAC; 2017. Available from: http://www.healthycanadians.gc.ca/publications/diseases-conditions-maladies-affections/fluwatch-2016-2017-02-surveillance-influenza/index-eng.php?_ga=1.147496691.591173311.1486470400
  2. Skowronski DM, Chambers C, Sabaiduc S, De Serres G, Dickinson JA, Winter AL, et al. Interim estimates of 2014/15 vaccine effectiveness against influenza A(H3N2) from Canada’s Sentinel Physician Surveillance Network, January 2015. Euro Surveill. 2015;20(4):21022.  https://doi.org/10.2807/1560-7917.ES2015.20.4.21022  PMID: 25655053 
  3. Skowronski DM, Chambers C, Sabaiduc S, De Serres G, Winter AL, Dickinson JA, et al. A perfect storm: Impact of genomic variation and serial vaccination on low influenza vaccine effectiveness during the 2014-2015 season. Clin Infect Dis. 2016;63(1):21-32.  https://doi.org/10.1093/cid/ciw176  PMID: 27025838 
  4. Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ, et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med. 2009;360(25):2605-15.  https://doi.org/10.1056/NEJMoa0903810  PMID: 19423869 
  5. Chen Y, Cui D, Zheng S, Yang S, Tong J, Yang D, et al. Simultaneous detection of influenza A, influenza B, and respiratory syncytial viruses and subtyping of influenza A H3N2 virus and H1N1 (2009) virus by multiplex real-time PCR. J Clin Microbiol. 2011;49(4):1653-6.  https://doi.org/10.1128/JCM.02184-10  PMID: 21270233 
  6. Allplex Respiratory Panel Assay. Seoul: Seegene. Available from: http://seegene.com/neo/en/products/respiratory/allplex_Rp_fp.php
  7. NxTAG Respiratory Pathogen Panel (RUO). Luminex. Available from: https://www.luminexcorp.com/clinical/ruo-products/nxtag-respiratory-pathogen-panel/
  8. Ndifon W, Wingreen NS, Levin SA. Differential neutralization efficiency of hemagglutinin epitopes, antibody interference, and the design of influenza vaccines. Proc Natl Acad Sci USA. 2009;106(21):8701-6.  https://doi.org/10.1073/pnas.0903427106  PMID: 19439657 
  9. Koel BF, Burke DF, Bestebroer TM, van der Vliet S, Zondag GC, Vervaet G, et al. Substitutions near the receptor binding site determine major antigenic change during influenza virus evolution. Science. 2013;342(6161):976-9.  https://doi.org/10.1126/science.1244730  PMID: 24264991 
  10. Public Health Agency of Canada (PHAC). FluWatch report: August 14 to August 27, 2016 (weeks 33-34). Ottawa: PHAC; 2016. Available from: https://www.canada.ca/en/public-health/services/publications/diseases-conditions/fluwatch-report-august-14-27-2016-weeks-33-34.html
  11. Public Health Agency of Canada (PHAC). FluWatch report: August 16 to August 29, 2015 (weeks 33 & 34). Ottawa: PHAC; 2015. Available from: https://www.canada.ca/en/public-health/services/publications/diseases-conditions/fluwatch-report-august-16-29-2015-weeks-33-34.html
  12. Public Health Agency of Canada (PHAC). FluWatch report: August 11 to August 24, 2013 (weeks 33 & 34). Ottawa: PHAC; 2013. Available from: http://publications.gc.ca/collections/collection_2013/aspc-phac/HP58-1-2013-34-eng.pdf
  13. Belongia EA, Simpson MD, King JP, Sundaram ME, Kelley NS, Osterholm MT, et al. Variable influenza vaccine effectiveness by subtype: a systematic review and meta-analysis of test-negative design studies. Lancet Infect Dis. 2016;16(8):942-51.  https://doi.org/10.1016/S1473-3099(16)00129-8  PMID: 27061888 
  14. European Centre for Disease Prevention and Control (ECDC). Risk assessment of seasonal influenza, EU/EEA, 2016-2017: Update, 25 January 2017. Stockholm: ECDC; 2017. Available from: http://ecdc.europa.eu/en/publications/Publications/Risk-assessment-seasonal-influenza-2016-2017-update.pdf
  15. Schanzer DL, Sevenhuysen C, Winchester B, Mersereau T. Estimating influenza deaths in Canada, 1992-2009. PLoS One. 2013;8(11):e80481.  https://doi.org/10.1371/journal.pone.0080481  PMID: 24312225 
  16. Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289(2):179-86.  https://doi.org/10.1001/jama.289.2.179  PMID: 12517228 
  17. Smith DJ, Forrest S, Ackley DH, Perelson AS. Variable efficacy of repeated annual influenza vaccination. Proc Natl Acad Sci USA. 1999;96(24):14001-6.  https://doi.org/10.1073/pnas.96.24.14001  PMID: 10570188 
  18. World Health Organization (WHO). Recommended composition of influenza virus vaccines for use in the 2016-2017 northern hemisphere influenza season. Geneva: WHO; 2016. Available from: http://www.who.int/influenza/vaccines/virus/recommendations/2016_17_north/en/
  19. The Francis Crick Institute. September 2016 interim report. London: The Crick Worldwide Influenza Centre (WIC); 2016. Available from: https://www.crick.ac.uk/media/326439/september_2016_interim_report.pdf
  20. European Centre for Disease Prevention and Control (ECDC). Influenza virus characterisation, summary Europe, September 2016. Stockholm: ECDC; 2016. Available from: http://ecdc.europa.eu/en/publications/Publications/influenza-virus-characterisation-september-2016.pdf
  21. Neher RA, Bedford T. nextflu: real-time tracking of seasonal influenza virus evolution in humans. Bioinformatics. 2015;31(21):3546-8. . Available from: http://nextflu.org/h3n2/3y/ https://doi.org/10.1093/bioinformatics/btv381  PMID: 26115986 
  22. Skowronski DM, Sabaiduc S, Chambers C, Eshaghi A, Gubbay JB, Krajden M, et al. Mutations acquired during cell culture isolation may affect antigenic characterisation of influenza A(H3N2) clade 3C.2a viruses. Euro Surveill. 2016;21(3):30112.  https://doi.org/10.2807/1560-7917.ES.2016.21.3.30112  PMID: 26836031 
  23. Popova L, Smith K, West AH, Wilson PC, James JA, Thompson LF, et al. Immunodominance of antigenic site B over site A of hemagglutinin of recent H3N2 influenza viruses. PLoS One. 2012;7(7):e41895.  https://doi.org/10.1371/journal.pone.0041895  PMID: 22848649 
  24. Abe Y, Takashita E, Sugawara K, Matsuzaki Y, Muraki Y, Hongo S. Effect of the addition of oligosaccharides on the biological activities and antigenicity of influenza A/H3N2 virus hemagglutinin. J Virol. 2004;78(18):9605-11.  https://doi.org/10.1128/JVI.78.18.9605-9611.2004  PMID: 15331693 
  25. Tate MD, Job ER, Deng Y-M, Gunalan V, Maurer-Stroh S, Reading PC. Playing hide and seek: how glycosylation of the influenza virus hemagglutinin can modulate the immune response to infection. Viruses. 2014;6(3):1294-316.  https://doi.org/10.3390/v6031294  PMID: 24638204 
  26. An Y, McCullers JA, Alymova I, Parsons LM, Cipollo JF. Glycosylation analysis of engineered H3N2 influenza A virus hemagglutinins with sequentially added historically relevant glycosylation sites. J Proteome Res. 2015;14(9):3957-69.  https://doi.org/10.1021/acs.jproteome.5b00416  PMID: 26202417 
  27. Leung VK, Cowling BJ, Feng S, Sullivan SG. Concordance of interim and final estimates of influenza vaccine effectiveness: a systematic review. Euro Surveill. 2016;21(16):30202.  https://doi.org/10.2807/1560-7917.ES.2016.21.16.30202  PMID: 27124573 
  28. Orenstein EW, De Serres G, Haber MJ, Shay DK, Bridges CB, Gargiullo P, et al. Methodologic issues regarding the use of three observational study designs to assess influenza vaccine effectiveness. Int J Epidemiol. 2007;36(3):623-31.  https://doi.org/10.1093/ije/dym021  PMID: 17403908 

Data & Media loading...

Supplementary data

Submit comment
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error