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Abstract

Introduction

The Canadian Sentinel Practitioner Surveillance Network reports vaccine effectiveness (VE) for the 2018/19 influenza A(H3N2) epidemic.

Aim

To explain a paradoxical signal of increased clade 3C.3a risk among 35–54-year-old vaccinees, we hypothesise childhood immunological imprinting and a cohort effect following the 1968 influenza A(H3N2) pandemic.

Methods

We assessed VE by test-negative design for influenza A(H3N2) overall and for co-circulating clades 3C.2a1b and 3C.3a. VE variation by age in 2018/19 was compared with amino acid variation in the haemagglutinin glycoprotein by year since 1968.

Results

Influenza A(H3N2) VE was 17% (95% CI: −13 to 39) overall: 27% (95% CI: −7 to 50) for 3C.2a1b and −32% (95% CI: −119 to 21) for 3C.3a. Among 20–64-year-olds, VE was −7% (95% CI: −56 to 26): 6% (95% CI: −49 to 41) for 3C.2a1b and −96% (95% CI: −277 to −2) for 3C.3a. Clade 3C.3a VE showed a pronounced negative dip among 35–54-year-olds in whom the odds of medically attended illness were > 4-fold increased for vaccinated vs unvaccinated participants (p < 0.005). This age group was primed in childhood to influenza A(H3N2) viruses that for two decades following the 1968 pandemic bore a serine at haemagglutinin position 159, in common with contemporary 3C.3a viruses but mismatched to 3C.2a vaccine strains instead bearing tyrosine.

Discussion

Imprinting by the first childhood influenza infection is known to confer long-lasting immunity focused toward priming epitopes. Our findings suggest vaccine mismatch may negatively interact with imprinted immunity. The immunological mechanisms for imprint-regulated effect of vaccine (I-REV) warrant investigation.

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/content/10.2807/1560-7917.ES.2019.24.46.1900585
2019-11-14
2019-12-12
http://instance.metastore.ingenta.com/content/10.2807/1560-7917.ES.2019.24.46.1900585
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References

  1. Skowronski DM, Leir S, Sabaiduc S, Murti M, Dickinson JA, Olsha R, et al. Interim estimates of 2018/19 vaccine effectiveness against influenza A(H1N1)pdm09, Canada, January 2019. Euro Surveill. 2019;24(4). 1900055.  https://doi.org/10.2807/1560-7917.ES.2019.24.4.1900055  PMID: 30696523 
  2. Skowronski DM, Leir S, De Serres G, Murti M, Dickinson JA, Winter A-L, et al. Children under 10 years of age were more affected by the 2018/19 influenza A(H1N1)pdm09 epidemic in Canada: ‎possible cohort effect following the 2009 influenza pandemic. Euro Surveill. 2019;24(15):1900104.  https://doi.org/10.2807/1560-7917.ES.2019.24.15.1900104  PMID: 30994107 
  3. Public Health Agency of Canada (PHAC). Influenza weekly reports 2018-19 season. FluWatch report: April 28 to May 4, 2019 (Week 18). Ottawa: PHAC; 2019. Available from: https://www.canada.ca/en/public-health/services/diseases/flu-influenza/influenza-surveillance/weekly-reports-2018-2019-season.html
  4. World Health Organization (WHO). WHO recommendations on the composition of influenza virus vaccines Geneva: WHO. [Accessed: 29 Oct 2019]. Available from: https://www.who.int/influenza/vaccines/virus/recommendations/en/
  5. Worldwide Influenza Centre, Francis Crick Institute. Annual and interim reports. London: Francis Crick Institute. [Accessed: 29 Oct 2019]. Available from: https://www.crick.ac.uk/research/worldwide-influenza-centre/annual-and-interim-reports/
  6. European Centre for Disease Prevention and Control (ECDC). Influenza virus characterization, summary Europe, June 2019. Stockholm: ECDC. [Accessed: 29 Oct 2019]. Available from: https://ecdc.europa.eu/en/publications-data/influenza-virus-characterisation-summary-europe-june-2019
  7. Nextstrain. Real-time tracking of influenza A/H3N2 evolution. [Accessed 29 October 2019]. Available from: https://nextstrain.org/flu/seasonal/h3n2/ha/6y
  8. Advisory Committee on Immunization Practices (ACIP). ACIP live meeting archive – June 2019. Agency updates; influenza vaccines. Atlanta: Centers for Disease Control and Prevention. [Accessed: 29 Oct 2019]. Available from: https://www.cdc.gov/vaccines/acip/meetings/live-mtg-2019-06.html
  9. Centers for Disease Control and Prevention (CDC). FluView: Weekly influenza surveillance report. 2018-2019 influenza season week 18 ending May 4, 2019. Atlanta: CDC. [Accessed: 29 Oct 2019]. Available from: https://www.cdc.gov/flu/weekly/weeklyarchives2018-2019/Week18.htm
  10. Flannery B, Kondor RJG, Chung JR, Gaglani M, Reis M, Zimmerman RK, et al. Spread of antigenically drifted influenza A(H3N2) viruses and vaccine effectiveness in the United States during the 2018-2019 season. J Infect Dis. 2019;jiz543.  https://doi.org/10.1093/infdis/jiz543  PMID: 31665373 
  11. 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 
  12. 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 
  13. 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 
  14. Zost SJ, Parkhouse K, Gumina ME, Kim K, Diaz Perez S, Wilson PC, et al. Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains. Proc Natl Acad Sci USA. 2017;114(47):12578-83.  https://doi.org/10.1073/pnas.1712377114  PMID: 29109276 
  15. 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 
  16. 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 
  17. Wu NC, Zost SJ, Thompson AJ, Oyen D, Nycholat CM, McBride R, et al. A structural explanation for the low effectiveness of the seasonal influenza H3N2 vaccine. PLoS Pathog. 2017;13(10):e1006682.  https://doi.org/10.1371/journal.ppat.1006682  PMID: 29059230 
  18. 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 
  19. Francis ME, King ML, Kelvin AA. Back to the future for influenza preimmunity-looking back at influenza virus history to infer the outcome of future infections. Viruses. 2019;11(2):E122.  https://doi.org/10.3390/v11020122  PMID: 30704019 
  20. Francis ME, McNeil M, Dawe NJ, Foley MK, King ML, Ross TM, et al. Historical H1N1 influenza virus imprinting increases vaccine protection by influencing the activity and sustained production of antibodies elicited at vaccination in ferrets. Vaccines (Basel). 2019;7(4):E133.  https://doi.org/10.3390/vaccines7040133  PMID: 31569351 
  21. Canadian Influenza Sentinel Practitioner Surveillance Network (SPSN). Influenza vaccine effectiveness estimates % (95% CI), 2004-05 to 2018-19 seasons. Vancouver: British Columbia Centre for Disease Control. [Accessed: 29 Oct 2019]. Available from: http://www.bccdc.ca/resource-gallery/Documents/Statistics%20and%20Research/Publications/Epid/Influenza%20and%20Respiratory/SPSN_VE_By_Year_Table.pdf
  22. Firth D. Bias reduction of maximum likelihood estimates. Biometrika. 1993;80(1):27-38.  https://doi.org/10.1093/biomet/80.1.27 
  23. Heinze G, Schemper M. A solution to the problem of separation in logistic regression. Stat Med. 2002;21(16):2409-19.  https://doi.org/10.1002/sim.1047  PMID: 12210625 
  24. Devika S, Jeyaseelan L, Sebastian G. Analysis of sparse data in logistic regression in medical research: A newer approach. J Postgrad Med. 2016;62(1):26-31.  https://doi.org/10.4103/0022-3859.173193  PMID: 26732193 
  25. Shu Y, McCauley J. GISAID: Global initiative on sharing all influenza data - from vision to reality. Euro Surveill. 2017;22(13):30494.  https://doi.org/10.2807/1560-7917.ES.2017.22.13.30494  PMID: 28382917 
  26. Katz JM, Hancock K, Xu X. Serologic assays for influenza surveillance, diagnosis and vaccine evaluation. Expert Rev Anti Infect Ther. 2011;9(6):669-83.  https://doi.org/10.1586/eri.11.51  PMID: 21692672 
  27. Katoh K, Standley DM. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol. 2013;30(4):772-80.  https://doi.org/10.1093/molbev/mst010  PMID: 23329690 
  28. Bodewes R, de Mutsert G, van der Klis FR, Ventresca M, Wilks S, Smith DJ, et al. Prevalence of antibodies against seasonal influenza A and B viruses in children in Netherlands. Clin Vaccine Immunol. 2011;18(3):469-76.  https://doi.org/10.1128/CVI.00396-10  PMID: 21209157 
  29. Public Health Agency of Canada. How healthy are Canadians? A trend analysis of the health of Canadians from a healthy living and chronic disease perspective. Ottawa: Government of Canada; 2017. Available from: https://www.canada.ca/en/public-health/services/publications/healthy-living/how-healthy-canadians.html#s3-3
  30. De Serres G, Skowronski DM, Wu XW, Ambrose CS. The test-negative design: validity, accuracy and precision of vaccine efficacy estimates compared to the gold standard of randomised placebo-controlled clinical trials. Euro Surveill. 2013;18(37):20585.  https://doi.org/10.2807/1560-7917.ES2013.18.37.20585  PMID: 24079398 
  31. Kissling E. Unprecedented low primary care influenza vaccine effectiveness against A(H3N2) among 15-64 year olds in 2018-19 in Europe. Euro Surveill. 2019. Forthcoming.
  32. Davenport FM, Hennessy AV. Predetermination by infection and by vaccination of antibody response to influenza virus vaccines. J Exp Med. 1957;106(6):835-50.  https://doi.org/10.1084/jem.106.6.835  PMID: 13481247 
  33. Francis T. On the doctrine of original antigenic sin. Proc Am Philos Soc. 1960;104(6):572-8.
  34. Monto AS, Malosh RE, Petrie JG, Martin ET. The doctrine of original antigenic sin: separating good from evil. J Infect Dis. 2017;215(12):1782-8.  https://doi.org/10.1093/infdis/jix173  PMID: 28398521 
  35. Skowronski DM, Hottes TS, McElhaney JE, Janjua NZ, Sabaiduc S, Chan T, et al. Immuno-epidemiologic correlates of pandemic H1N1 surveillance observations: higher antibody and lower cell-mediated immune responses with advanced age. J Infect Dis. 2011;203(2):158-67.  https://doi.org/10.1093/infdis/jiq039  PMID: 21288814 
  36. Worobey M, Han GZ, Rambaut A. Genesis and pathogenesis of the 1918 pandemic H1N1 influenza A virus. Proc Natl Acad Sci USA. 2014;111(22):8107-12.  https://doi.org/10.1073/pnas.1324197111  PMID: 24778238 
  37. Gostic KM, Ambrose M, Worobey M, Lloyd-Smith JO. Potent protection against H5N1 and H7N9 influenza via childhood hemagglutinin imprinting. Science. 2016;354(6313):722-6.  https://doi.org/10.1126/science.aag1322  PMID: 27846599 
  38. Viboud C, Epstein SL. First flu is forever. Science. 2016;354(6313):706-7.  https://doi.org/10.1126/science.aak9816  PMID: 27846592 
  39. Budd AP, Beacham L, Smith CB, Garten RJ, Reed C, Kniss K, et al. Birth cohort effects in influenza surveillance data: evidence that first influenza infection affects later influenza-associated illness. J Infect Dis. 2019;220(5):820-9.  https://doi.org/10.1093/infdis/jiz201  PMID: 31053844 
  40. Li Y, Myers JL, Bostick DL, Sullivan CB, Madara J, Linderman SL, et al. Immune history shapes specificity of pandemic H1N1 influenza antibody responses. J Exp Med. 2013;210(8):1493-500.  https://doi.org/10.1084/jem.20130212  PMID: 23857983 
  41. Linderman SL, Chambers BS, Zost SJ, Parkhouse K, Li Y, Herrmann C, et al. Potential antigenic explanation for atypical H1N1 infections among middle-aged adults during the 2013-2014 influenza season. Proc Natl Acad Sci USA. 2014;111(44):15798-803.  https://doi.org/10.1073/pnas.1409171111  PMID: 25331901 
  42. Linderman SL, Hensley SE. Antibodies with ‘original antigenic sin’ properties are valuable components of secondary immune responses to influenza viruses. PLoS Pathog. 2016;12(8):e1005806.  https://doi.org/10.1371/journal.ppat.1005806  PMID: 27537358 
  43. Kosikova M, Li L, Radvak P, Ye Z, Wan X-F, Xie H. Imprinting of repeated influenza A/H3 exposures on antibody quantity and antibody quality: implications for seasonal vaccine strain selection and vaccine performance. Clin Infect Dis. 2018;67(10):1523-32.  https://doi.org/10.1093/cid/ciy327  PMID: 29672713 
  44. Treanor J. What happens next depends on what happened first. Clin Infect Dis. 2018;67(10):1533-4.  https://doi.org/10.1093/cid/ciy330  PMID: 29672677 
  45. Skowronski DM, Chambers C, Sabaiduc S, De Serres G, Winter A-L, Dickinson JA, et al. Beyond antigenic match: possible agent-host and immuno-epidemiological influences on influenza vaccine effectiveness during the 2015-2016 season in Canada. J Infect Dis. 2017;216(12):1487-500.  https://doi.org/10.1093/infdis/jix526  PMID: 29029166 
  46. Flannery B, Smith C, Garten RJ, Levine MZ, Chung JR, Jackson ML, et al. Influence of birth cohort on effectiveness of 2015-2016 influenza vaccine against medically attended illness due to 2009 pandemic influenza A(H1N1) virus in the United States. J Infect Dis. 2018;218(2):189-96.  https://doi.org/10.1093/infdis/jix634  PMID: 29361005 
  47. Lewnard JA, Cobey S. Immune history and influenza vaccine effectiveness. Vaccines (Basel). 2018;6(2):E28.  https://doi.org/10.3390/vaccines6020028  PMID: 29883414 
  48. 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 
  49. Skowronski DM, Chambers C, De Serres G, Sabaiduc S, Winter AL, Dickinson JA, et al. Serial vaccination and the antigenic distance hypothesis: effects on influenza vaccine effectiveness during A(H3N2) epidemics in Canada, 2010-2011 to 2014-2015. J Infect Dis. 2017;215(7):1059-99.  https://doi.org/10.1093/infdis/jix074  PMID: 28180277 
  50. Gotoff R, Tamura M, Janus J, Thompson J, Wright P, Ennis FA. Primary influenza A virus infection induces cross-reactive antibodies that enhance uptake of virus into Fc receptor-bearing cells. J Infect Dis. 1994;169(1):200-3.  https://doi.org/10.1093/infdis/169.1.200  PMID: 8277183 
  51. Rajão DS, Chen H, Perez DR, Sandbulte MR, Gauger PC, Loving CL, et al. Vaccine-associated enhanced respiratory disease is influenced by haemagglutinin and neuraminidase in whole inactivated influenza virus vaccines. J Gen Virol. 2016;97(7):1489-99.  https://doi.org/10.1099/jgv.0.000468  PMID: 27031847 
  52. Rajao DS, Sandbulte MR, Gauger PC, Kitikoon P, Platt R, Roth JA, et al. Heterologous challenge in the presence of maternally-derived antibodies results in vaccine-associated enhanced respiratory disease in weaned piglets. Virology. 2016;491:79-88.  https://doi.org/10.1016/j.virol.2016.01.015  PMID: 26874588 
  53. Sauter P, Hober D. Mechanisms and results of the antibody-dependent enhancement of viral infections and role in the pathogenesis of coxsackievirus B-induced diseases. Microbes Infect. 2009;11(4):443-51.  https://doi.org/10.1016/j.micinf.2009.01.005  PMID: 19399964 
  54. Takada A, Kawaoka Y. Antibody-dependent enhancement of viral infection: molecular mechanisms and in vivo implications. Rev Med Virol. 2003;13(6):387-98.  https://doi.org/10.1002/rmv.405  PMID: 14625886 
  55. Skowronski DM, De Serres G, Crowcroft NS, Janjua NZ, Boulianne N, Hottes TS, et al. Canadian SAVOIR Team. Association between the 2008-09 seasonal influenza vaccine and pandemic H1N1 illness during Spring-Summer 2009: four observational studies from Canada. PLoS Med. 2010;7(4):e1000258.  https://doi.org/10.1371/journal.pmed.1000258  PMID: 20386731 
  56. Skowronski DM, Hamelin ME, De Serres G, Janjua NZ, Li G, Sabaiduc S, et al. Randomized controlled ferret study to assess the direct impact of 2008-09 trivalent inactivated influenza vaccine on A(H1N1)pdm09 disease risk. PLoS One. 2014;9(1):e86555.  https://doi.org/10.1371/journal.pone.0086555  PMID: 24475142 
  57. Monsalvo AC, Batalle JP, Lopez MF, Krause JC, Klemenc J, Hernandez JZ, et al. Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes. Nat Med. 2011;17(2):195-9.  https://doi.org/10.1038/nm.2262  PMID: 21131958 
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