Effective reproduction number (<i>R_eff</i>) according to various scenarios of population immunity by initial basic reproduction number (<i>R₀</i>) assumed.

<p><b>SPR</b> = Sero-protection rate – defined as the proportion (%) considered sero-protected on the basis of having met or exceeded the specified antibody titre threshold; <b>pre-H1N1pdm09:</b> 2009 H1N1 pandemic virus; SPR presented based on PRE-pandemic antibody levels measured in 2009 or earlier; <b>post-H1N1pdm09:</b> 2009 H1N1 pandemic virus; SPR presented based on POST-pandemic antibody levels measured in fall 2010; <b>H3N2v:</b> swine-origin H3N2 variant strain; SPR presented based on antibody levels measured in sera collected in fall 2010; <b>post-Brisbane:</b> a contemporary seasonal human influenza H3N2 virus; SPR presented based post-circulation antibody levels in sera collected in fall 2010; <b>SPR40:</b> the proportion considered sero-protected according to the standard hemagglutination inhibition (HI) titre threshold of 40; <b>½SPR40:</b> assumes half the individuals meeting SPR40 are considered sero-protected; <b>SPR80:</b> the proportion considered sero-protected according to a hemagglutination inhibition (HI) titre threshold of 80.</p

Main input parameter values for Greater Vancouver Area (GVA) contact network model.

<p>HI = hemagglutination inhibition assay; SPR = Sero-protection rate – defined as the proportion (%) considered sero-protected on the basis of having met or exceeded the specified antibody titre threshold.</p><p><b>pre-H1N1pdm09</b>: 2009 H1N1 pandemic virus; SPR based on PRE-pandemic antibody levels in 2009 or earlier.</p><p><b>post-H1N1pdm09</b>: 2009 H1N1 pandemic virus; SPR based on POST-pandemic antibody levels fall 2010.</p><p><b>H3N2v:</b> swine-origin H3N2 variant strain; SPR based on antibody levels in fall 2010.</p><p><b>post-Brisbane</b>: a seasonal human influenza H3N2 virus; SPR based on antibody levels fall 2010.</p>a<p>Statistics Canada 2006 Community Profiles [<a href="http://www12.statcan.ca/census-recensement/2006/dp-pd/prof/92-591/index.cfm?Lang=E" target="_blank">http://www12.statcan.ca/census-recensement/2006/dp-pd/prof/92-591/index.cfm?Lang=E</a>].</p>b<p>The same typical seasonal influenza parameter values were applied to each of the three influenza viruses assessed, recognizing their human influenza virus ancestral origins.</p>c<p>Based on 100% SPR defined at HI titre ≥40; ^dBased on 50%SPR defined at HI titre ≥40; ^e100%SPR defined at HI titre ≥80.</p><p>Note that a blended composite of sero-protection based on a gradient of immunity defined as <b>¼</b>SPR20, ½SPR40, ¾SPR80 and 100% SPR160 was also explored (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054015#pone.0054015.s003" target="_blank">Table S1</a> and narrative).</p

Age-stratified epidemic attack rates by scenario and assumed basic reproduction number (<i>R₀</i> = 1.40). SPR

<p> = Sero-protection rate – defined as the proportion (%) considered sero-protected on the basis of having met or exceeded the specified antibody titre threshold; <b>pre-H1N1pdm09:</b> 2009 H1N1 pandemic virus; SPR presented based on PRE-pandemic antibody levels measured in 2009 or earlier; <b>post-H1N1pdm09:</b> 2009 H1N1 pandemic virus; SPR presented based on POST-pandemic antibody levels measured in fall 2010; <b>H3N2v:</b> swine-origin H3N2 variant strain; SPR presented based on antibody levels measured in sera collected in fall 2010; <b>post-Brisbane:</b> a contemporary seasonal human influenza H3N2 virus; SPR presented based post-circulation antibody levels in sera collected in fall 2010; <b>SPR40:</b> the proportion considered sero-protected according to the standard hemagglutination inhibition (HI) titre threshold of 40; <b>½SPR40:</b> assumes half the individuals meeting SPR40 are considered sero-protected; <b>SPR80:</b> the proportion considered sero-protected according to a hemagglutination inhibition (HI) titre threshold of 80 Overall attack rates are indicated by the horizontal line. Based on simulations using age-specific parameters, these overall attack rates were derived as the total number of infections divided by the total population size.</p

Cross-strain influenza A(H3N2) antibody responses measured by HI assay.^*

<p>HI = hemagglutination inhibition; TIV  =  trivalent inactivated influenza vaccine. Note that undetectable titres <10 were assigned a value of 5.</p>*<p>Unit of analysis pooled sera from 5 mice, thus 10 pools from 50 mice were available for this experiment.</p>a<p>Measured two weeks after specified TIV dose;</p>b<p>Measured two months after specified TIV dose.</p>†<p>Compared to pre-immunization for priming antigens; compared to immediately preceding titre for boosting antigens.</p><p>Brisbane-like  =  A/Uruguay/716/2007(NYMC 175C)(H3N2) considered antigenically equivalent to the WHO recommended A/Brisbane/10/2007(H3N2) component of the 2008–09 northern hemisphere TIV.</p><p>Perth  =  A/Perth/16/2009(H3N2)-like, component of the northern hemisphere 2010–11 TIV.</p

Cross-lineage influenza B antibody responses measured by HI and MN assays.^*

<p>HI  =  hemagglutination inhibition; MN  =  microneutralization; TIV  =  trivalent inactivated influenza vaccine. Note that undetectable titres <10 were assigned a value of 5.</p>*<p>Unit of analysis pooled sera from 5 mice, thus 10 pools from 50 mice were available for this experiment.</p>a<p>Measured two weeks after specified TIV dose;</p>b<p>Measured two months after specified TIV dose.</p>†<p>Compared to pre-immunization for initiating antigens; compared to immediately preceding titre for boosting antigens.</p><p>Yamagata  =  Florida/4/06(Yamagata)-like, the Yamagata lineage antigen included in the northern hemisphere 2008–09 TIV.</p><p>Victoria  =  Brisbane/60/08(Victoria)-like, the Victoria lineage antigen included in the northern hemisphere 2009–10 and 2010–11 TIV.</p

Cross-strain influenza A(H1N1) antibody responses measured by HI assay.^*

<p>HI  =  hemagglutination inhibition; TIV  =  trivalent inactivated influenza vaccine. Note that undetectable titres <10 were assigned a value of 5.</p>*<p>Unit of analysis pooled sera from 5 mice, thus 10 pools from 50 mice were available for this experiment.</p>a<p>Measured two weeks after specified TIV dose;</p>b<p>Measured two months after specified TIV dose.</p>†<p>Compared to pre-immunization for initiating antigens; compared to immediately preceding titre for boosting antigens.</p><p>Brisbane  =  A/Brisbane/59/2007(H1N1)-like, component of the northern hemisphere 2008–09 and 2009–10 TIV.</p><p>California  =  A/California/07/2009(H1N1)-like, component of the northern hemisphere 2010–11 TIV.</p

Hospitalization (pneumonia, influenza, or acute respiratory disease; panel a) and all-cause mortality (panel b) counts and rates by immunization status and influenza vaccine effectiveness estimates against hospitalization (panel a) and all-cause mortality (panel b), adjusted for age, prior medical visits, prior influenza vaccination, and prior pneumococcal vaccination, 2000–01 to 2005–06.

<p><b>Note.</b> Numbers adjacent to rates represent numerator counts of hospitalizations per period and immunization status stratum; numbers in ‘Aggregate Years’ section represent median counts per period. There is no pre-period for 2003–04 owing to early start of influenza period. Hospitalization defined as admission with pneumonia, influenza, or acute respiratory disease listed as most responsible diagnosis. IVE = influenza vaccine effectiveness. * Aggr. = data aggregated across all 6 seasons 2000–01 to 2005–06 (2003–04 excluded for all-cause mortality). ^† Approximate influenza A versus B circulation (based on national summaries <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0022618#pone.0022618-Skowronski1" target="_blank">[45]</a>) and match to vaccine components.</p

Aggregated hospitalization (pneumonia, influenza, or acute respiratory disease; panel a) and all-cause mortality (panel b) rates by prior & current immunization status, by period, 2000–01 to 2005–06.

<p><b>Note.</b> Based on GEE model adjusting for age, prior medical visits, and prior pneumococcal vaccination, and accounting for year-to-year variation. 2003–04 excluded from pre-influenza period analyses for hospitalization and from all analysis periods for mortality owing to early start of influenza period. Hospitalization defined as admission with pneumonia, influenza, or acute respiratory disease listed as most responsible diagnosis.</p

Influenza vaccine effectiveness against hospitalization and all-cause mortality during influenza periods, 2000–01 to 2005–06 with and without adjustment for multiple and select covariates.

<p><b>Note.</b> IVE = influenza vaccine effectiveness; CI = confidence interval; Hosp = hospitalization with pneumonia, influenza, or acute respiratory disease listed as most responsible admission diagnosis; Death = all-cause mortality; SES = socioeconomic status.</p>a<p>Adjusted for all following covariates: age, sex, socio-economic status, urban residency, prior influenza immunization (two year), prior pneumococcal immunization, medical visits prior year, and Elixhauser index.</p>b<p>Adjusted for select influential covariates of age, prior influenza (two year) and pneumococcal immunization and medical visits prior year.</p>c<p>Matched on propensity scores, calculated based on age, sex, socio-economic status, urban residency, prior influenza immunization (two year), prior pneumococcal immunization, medical visits prior year, and Elixhauser index.</p>d<p>Select adjustment includes pneumococcal immunization, medical visits prior year, and age.</p>e<p>Data aggregated across all six seasons for hospitalization and across all seasons except 2003–04 for mortality.</p

Aggregate influenza vaccine effectiveness against hospitalization and all-cause mortality estimated by GEE with adjustment, propensity score matching, and stratification: 2000–01 to 2005–06.

<p><b>Note.</b> IVE = influenza vaccine effectiveness; CI = confidence interval.</p>a<p>All covariates include: age, sex, socio-economic status, urban residency, prior influenza immunization (two year), prior pneumococcal immunization, medical visits prior year, and Elixhauser index;</p>b<p>Select covariates include: age, prior influenza immunization (two year), pneumococcal immunization, medical visits prior year;</p>c<p>Matched on propensity scores derived based on all covariates: age, sex, socio-economic status, urban residency, prior influenza immunization (two year), prior pneumococcal immunization, medical visits prior year, and Elixhauser index;</p>d<p>Select adjustment includes: age, prior pneumococcal immunization, medical visits prior year;</p>e<p>Pneumonia, influenza, or acute respiratory disease listed as most responsible admission diagnosis;</p>f<p>Pre-influenza period estimates for hospitalization do not include 2003–04;</p>g<p>2003–04 year excluded from all estimates related to all-cause mortality since the pre-influenza period constitutes the main comparison period for that outcome and was missing for 2003–04 owing to early influenza period.</p