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The Canadian Sentinel Practitioner Surveillance Network estimated vaccine effectiveness (VE) during the unusually early 2022/23 influenza A(H3N2) epidemic. Like vaccine, circulating viruses were clade 3C.2a1b.2a.2, but with genetic diversity affecting haemagglutinin positions 135 and 156, and reassortment such that H156 viruses acquired neuraminidase from clade 3C.2a1b.1a. Vaccine provided substantial protection with A(H3N2) VE of 54% (95% CI: 38 to 66) overall. VE was similar against H156 and vaccine-like S156 viruses, but with potential variation based on diversity at position 135.

The evolving proportion of the population considered immunologically naive versus primed for more efficient immune memory response to SARS-CoV-2 has implications for risk assessment. We sought to chronicle vaccine- and infection-induced seroprevalence across the first 7 waves of the COVID-19 pandemic in British Columbia, Canada.During 8 cross-sectional serosurveys conducted between March 2020 and August 2022, we obtained anonymized residual sera from children and adults who attended an outpatient laboratory network in the Lower Mainland (Greater Vancouver and Fraser Valley). We used at least 3 immunoassays per serosurvey to detect SARS-CoV-2 spike and nucleocapsid antibodies. We assessed any seroprevalence (vaccineor infection-induced, or both), defined by positivity on any 2 assays, and infection-induced seroprevalence, also defined by dual-assay positivity but requiring both antinucleocapsid and antispike detection. We used estimates of infection-induced seroprevalence to explore underascertainment of infections by surveillance case reports.By January 2021, we estimated that any seroprevalence remained less than 5%, increasing with vaccine rollout to 56% by May-June 2021, 83% by September-October 2021 and 95% by March 2022. Infection-induced seroprevalence remained less than 15% through September-October 2021, increasing across Omicron waves to 42% by March 2022 and 61% by July-August 2022. By August 2022, 70%-80% of children younger than 20 years and 60%-70% of adults aged 20-59 years had been infected, but fewer than half of adults aged 60 years and older had been infected. Compared with estimates of infection-induced seroprevalence, surveillance case reports underestimated infections 12-fold between September 2021 and March 2022 and 92-fold between March 2022 and August 2022.By August 2022, most children and adults younger than 60 years had evidence of both SARS-CoV-2 vaccination and infection. As previous evidence suggests that a history of both exposures may induce stronger, more durable hybrid immunity than either exposure alone, older adults - who have the lowest infection rates but highest risk of severe outcomes - continue to warrant prioritized vaccination.

Influenza virus circulation virtually ceased in Canada during the COVID-19 pandemic, re-emerging with the relaxation of restrictions in spring 2022. Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network reports 2021/22 vaccine effectiveness of 36% (95% CI: −38 to 71) against late-season illness due to influenza A(H3N2) clade 3C.2a1b.2a.2 viruses, considered antigenically distinct from the 3C.2a1b.2a.1 vaccine strain. Findings reinforce the World Health Organization’s decision to update the 2022/23 northern hemisphere vaccine to a more representative A(H3N2) clade 3C.2a1b.2a.2 strain.

BackgroundWe chronicle SARS-CoV-2 sero-prevalence through eight cross-sectional sero-surveys (snapshots) in the Lower Mainland (Greater Vancouver and Fraser Valley), British Columbia, Canada from March 2020 to August 2022.MethodsAnonymized-residual sera were obtained from children and adults attending an outpatient laboratory network. Sera were tested with at least three immuno-assays per snapshot to detect spike (S1) and/or nucleocapsid protein (NP) antibodies. Sero-prevalence was defined by dual-assay positivity, including any or infection-induced, the latter requiring S1+NP antibody detection from January 2021 owing to vaccine availability. Infection-induced estimates were used to assess the extent to which surveillance case reports under-estimated infections.ResultsSero-prevalence was ≤1% by the 3rd snapshot in September 2020 and th). Following vaccine roll-out, sero-prevalence increased to >55% by May/June 2021 (5th), ∼80% by September/October 2021 (6th), and >95% by March 2022 (7th). In all age groups, infection-induced sero-prevalence remained th) and ∼60% by July/August 2022 (8th). By August 2022, at least 70-80% of children ≤19 years, 60-70% of adults 20-59 years, but ∼40% of adults ≥60 years had been infected. Surveillance case reports under-estimated infections by 12-fold between the 6th-7th and 92-fold between the 7th-8th snapshots.InterpretationBy August 2022, most children and adults had acquired SARS-CoV-2 vaccine and infection exposures, resulting in more robust hybrid immunity. Conversely the elderly, still at greatest risk of severe outcomes, remain largely-dependent on vaccine-induced protection alone, and should be prioritized for additional doses.

Influenza viruses continually evolve to evade population immunity, and the different lineages are assigned into clades based on shared mutations. We have developed a publicly available computational workflow, the Influenza Classification Suite, for rapid clade mapping of sequenced influenza viruses. This suite provides a user‐friendly workflow implemented in Galaxy to automate clade calling and antigenic site extraction. Workflow input includes clade definition and amino acid index array files, which can be customized to identify any clades of interest. The Influenza Classification Suite provides rapid, high‐resolution understanding of circulating influenza strain evolution to inform influenza vaccine effectiveness and the need for potential vaccine reformulation.

BackgroundThe province of British Columbia (BC) has been recognized for successful SARS-CoV-2 control, with surveillance data showing amongst the lowest case and death rates in Canada. We estimate sero-prevalence for two periods flanking the start (March) and end (May) of first-wave mitigation measures in BC.MethodsSerial cross-sectional sampling was conducted using anonymized residual sera obtained from an outpatient laboratory network, including children and adults in the Greater Vancouver Area (population ∼3 million) where community attack rates were expected to be highest. Screening used two chemiluminescent immuno-assays for spike (S1) and nucleocapsid antibodies. Samples sero-positive on either screening assay were assessed by a third assay targeting the S1 receptor binding domain plus a neutralization assay. Age-standardized sero-prevalence estimates were based on dual-assay positivity. The May sero-prevalence estimate was extrapolated to the source population to assess surveillance under-ascertainment, quantified as the ratio of estimated infections versus reported cases.ResultsSerum collection dates spanned March 5-13 and May 15-27, 2020. In March, two of 869 specimens were dual-assay positive, with age-standardized sero-prevalence of 0.28% (95%CI=0.03-0.95). Neither specimen had detectable neutralizing antibodies. In May, four of 885 specimens were dual-assay positive, with age-standardized sero-prevalence of 0.55% (95%CI=0.15-1.37%). All four specimens had detectable neutralizing antibodies. We estimate ∼8 times more infections than reported cases.ConclusionsLess than 1% of British Columbians had been infected with SARS-CoV-2 when first-wave mitigation measures were relaxed in May 2020. Our findings indicate successful suppression of community transmission in BC, but also substantial residual susceptibility. Further sero-survey snapshots are planned as the pandemic unfolds.Key pointsCross-sectional sampling of anonymized residual sera at the start and end of first-wave mitigation measures in British Columbia, Canada shows SARS-CoV-2 sero-prevalence below 1% throughout the winter-spring 2020. Findings indicate successful suppression of community transmission but also substantial residual susceptibility.

Influenza vaccine effectiveness against influenza and noninfluenza respiratory viruses (NIRVs) was assessed by test-negative design using historic datasets of the community-based Canadian Sentinel Practitioner Surveillance Network, spanning 2010–2011 to 2016–2017. Vaccine significantly reduced the risk of influenza illness by >40% with no effect on coronaviruses or other NIRV risk.

Interim results from Canada's Sentinel Practitioner Surveillance Network show that during a season characterised by early co-circulation of influenza A and B viruses, the 2019/20 influenza vaccine has provided substantial protection against medically-attended influenza illness. Adjusted VE overall was 58% (95% confidence interval (CI): 47 to 66): 44% (95% CI: 26 to 58) for A(H1N1)pdm09, 62% (95% CI: 37 to 77) for A(H3N2) and 69% (95% CI: 57 to 77) for influenza B viruses, predominantly B/Victoria lineage.

Striped skunks (skunks) are susceptible to respiratory infection by influenza A viruses (IAV). As they are common synanthropes, maintenance of IAV in skunks could provide a source of infection for humans. We previously studied the nasal turbinates, lungs and faeces of 50 free-ranging skunks for the presence of IAV and identified two individuals with influenza A(H1N1)pdm09 infection during the 2009/2010 and 2013/2014 flu seasons. Subsequent to publication of that study, ferrets were shown to preferentially replicate and harbour A(H1N1)pdm09 in the soft palate, a site which had not been investigated in the skunks. From March 2015 to May 2016, we surveyed a convenience sample of 80 free-ranging urban skunks for IAV in soft palate, nasal turbinates and lungs. The newly emergent influenza A(H1N1)pdm09 clade 6B.1 was detected at all three sites in one skunk with acute rhinitis in February 2016. Clade 6B.1 was the dominant clade in circulation during the 2015/2016 flu season. As the skunk was detected at the height of flu season, reverse zoonosis was considered the most probable source of infection.

Vaccine effectiveness (VE) against influenza B was derived separately for Victoria and Yamagata lineages across 8 seasons (2010–2011 to 2017–2018) in Canada when trivalent influenza vaccine was predominantly used. VE was ≥50% regardless of lineage match to circulating viruses, except when the vaccine strain was unchanged from the prior season.

Summary Age-related differences in influenza B lineage infection were assessed by the community-based Canadian Sentinel Practitioner Surveillance Network between 2010–2011 and 2015–2016. Influenza B(Victoria) cases were on average 20 years younger than B(Yamagata) cases, with the latter showing a bimodal age distribution., Age-related differences in influenza B lineage detection were explored in the community-based Canadian Sentinel Practitioner Surveillance Network (SPSN) from 2010–2011 to 2015–2016. Whereas >80% of B(Victoria) cases were

Background 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). Methods 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. Results 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%). Conclusions 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.

An increase in hospital admissions for influenza occurred during the summer of 2015 at an acute care facility in Vancouver, British Columbia, Canada. Investigation identified 25 patients with recent history of cruise ship travel to Alaska. All characterized influenza A viruses were A(H3N2). We describe patient treatment regimens and outcomes.

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 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.

Background The influenza A(H3N2) vaccine was updated from clade 3C.3a in 2015–2016 to 3C.2a for 2016–2017 and 2017–2018. Circulating 3C.2a viruses showed considerable hemagglutinin glycoprotein diversification and the egg-adapted vaccine also bore mutations. Methods Vaccine effectiveness (VE) in 2016–2017 and 2017–2018 was assessed by test-negative design, explored by A(H3N2) phylogenetic subcluster and prior season’s vaccination history. Results In 2016–2017, A(H3N2) VE was 36% (95% confidence interval [CI], 18%–50%), comparable with (43%; 95% CI, 24%–58%) or without (33%; 95% CI, −21% to 62%) prior season’s vaccination. In 2017–2018, VE was 14% (95% CI, −8% to 31%), lower with (9%; 95% CI, −18% to 30%) versus without (45%; 95% CI, −7% to 71%) prior season’s vaccination. In 2016–2017, VE against predominant clade 3C.2a1 viruses was 33% (95% CI, 11%–50%): 18% (95% CI, −40% to 52%) for 3C.2a1a defined by a pivotal T135K loss of glycosylation; 60% (95% CI, 19%–81%) for 3C.2a1b (without T135K); and 31% (95% CI, 2%–51%) for other 3C.2a1 variants (with/without T135K). VE against 3C.2a2 viruses was 45% (95% CI, 2%–70%) in 2016–2017 but 15% (95% CI, −7% to 33%) in 2017–2018 when 3C.2a2 predominated. VE against 3C.2a1b in 2017–2018 was 37% (95% CI, −57% to 75%), lower at 12% (95% CI, −129% to 67%) for a new 3C.2a1b subcluster (n = 28) also bearing T135K. Conclusions Exploring VE by phylogenetic subcluster and prior vaccination history reveals informative heterogeneity. Pivotal mutations affecting glycosylation sites, and repeat vaccination using unchanged antigen, may reduce VE.

Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network assessed interim 2018/19 vaccine effectiveness (VE) against predominant influenza A(H1N1)pdm09 viruses. Adjusted VE was 72% (95% confidence interval: 60 to 81) against medically attended, laboratory-confirmed influenza A(H1N1)pdm09 illness. This substantial vaccine protection was observed in all age groups, notably young children who appeared to be disproportionately affected. Sequence analysis identified heterogeneity in emerging clade 6B.1 viruses but no dominant drift variant.

Introduction Findings from the community-based Canadian Sentinel Practitioner Surveillance Network (SPSN) suggest children were more affected by the 2018/19 influenza A(H1N1)pdm09 epidemic. Aim To compare the age distribution of A(H1N1)pdm09 cases in 2018/19 to prior seasonal influenza epidemics in Canada. Methods The age distribution of unvaccinated influenza A(H1N1)pdm09 cases and test-negative controls were compared across A(H1N1)pdm09-dominant epidemics in 2018/19, 2015/16 and 2013/14 and with the general population of SPSN provinces. Similar comparisons were undertaken for influenza A(H3N2)-dominant epidemics. Results In 2018/19, more influenza A(H1N1)pdm09 cases were under 10 years old than controls (29% vs 16%; p Conclusion Children under 10 years old contributed more to outpatient A(H1N1)pdm09 medical visits in 2018/19 than prior seasonal epidemics in Canada. In 2018/19, all children under 10 years old were born after the 2009 A(H1N1)pdm09 pandemic and therefore lacked pandemic-induced immunity. In addition, more than half those born after 2009 now attend school (i.e. 5–9-year-olds), a socio-behavioural context that may enhance transmission and did not apply during prior A(H1N1)pdm09 epidemics.

BACKGROUND Canada's Sentinel Physician Surveillance Network links genetic, antigenic, and vaccine effectiveness (VE) measures in an integrated platform of influenza monitoring, described here for the 2013-2014 influenza season of resurgent A(H1N1)pdm09 and late-season type B activity. METHODS VE was estimated as [1 - odds ratio] × 100% and compared vaccination status between individuals who tested positive (cases) and those who tested negative (controls) for influenza virus. Vaccine-virus relatedness was assessed by genomic sequence analysis and hemagglutination inhibition assays. RESULTS Analyses included 1037 controls (of whom 33% were vaccinated) and 663 cases (of whom 14% were vaccinated). A total of 415 cases tested positive for A(H1N1)pdm09 virus, 15 tested positive for A(H3N2) virus, 191 tested positive for B/Yamagata-lineage virus, 6 tested positive for B/Victoria-lineage virus, and 36 tested positive for viruses of unknown subtype or lineage. A(H1N1)pdm09 viruses belonged to clade 6B, distinguished by a K163Q substitution, but remained antigenically similar to the A/California/07/2009-like vaccine strain, with an adjusted VE of 71% (95% confidence interval [CI], 58%-80%). Most B/Yamagata-lineage viruses (83%) clustered phylogenetically with the prior (ie, 2012-2013) season's B/Wisconsin/01/2010-like clade 3 vaccine strain, while only 17% clustered with the current (ie, 2013-2014) season's B/Massachusetts/02/2012-like clade 2 vaccine strain. The adjusted VE for B/Yamagata-lineage virus was 73% (95% CI, 57%-84%), with a lower VE obtained after partial calendar-time adjustment for clade-mismatched B/Wisconsin/01/2010-like virus (VE, 63%; 95% CI, 41%-77%), compared with that for clade-matched B/Massachusetts/02/2012-like virus (VE, 88%; 95% CI, 48%-97%). No A(H3N2) viruses clustered with the A/Texas/50/2012-like clade 3C.1 vaccine strain, and more than half were antigenically mismatched, but sparse data did not support VE estimation. CONCLUSIONS VE corresponded with antigenically conserved A(H1N1)pdm09 and lineage-matched B/Yamagata viruses with clade-level variation. Surveillance linking genotypic, phenotypic, and epidemiologic measures of vaccine-virus relatedness and effectiveness could better inform predictions of vaccine performance and reformulation.

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.

Background We estimate vaccine effectiveness (VE) against both influenza A/subtypes and B/lineages in Canada for the 2011-2012 trivalent inactivated influenza vaccine (TIV) with components entirely unchanged from the 2010-2011 TIV and in the context of phenotypic and genotypic characterization of circulating viruses. Methods In a test-negative case-control study VE was estimated as [1-(adjusted)OddsRatio] × 100 for RT-PCR-confirmed influenza in vaccinated vs nonvaccinated participants. Viruses were characterized by hemagglutination inhibition (HI) and sequencing of antigenic sites of the hemagglutinin (HA) gene. Results There were 1507 participants. VE against A(H1N1)pdm09 was 80% (95% confidence interval [CI], 52%-92%): circulating viruses were HI-characterized as vaccine-matched and bore just 2 aminoacid (AA) differences from vaccine. VE against A/H3N2 was 51% (95% CI, 10%-73%): circulating viruses were HI-characterized as vaccine-related but bore ≥11AA differences from vaccine. VE against influenza B was 51% (95% CI, 26%-67%) in total: 71% (95% CI, 40%-86%) for lineage-matched B/Victoria and 27% (95% CI, -21% to 56%) for lineage-mismatched B/Yamagata. For both influenza A and B types, VE was similar among recipients of either 2010-2011 or 2011-2012 TIV alone, higher when vaccinated both seasons. Conclusions Phenotypic and genotypic characterization of circulating and vaccine viruses enhances understanding of TIV performance, shown in 2011-2012 to be substantial against well-conserved A(H1N1)pdm09 and lineage-matched influenza B, suboptimal against genetic-variants of A/H3N2, and further reduced against lineage-mismatched influenza B. With unchanged vaccine components, protection may extend beyond a single season.

Using a test-negative design, the Canadian Sentinel Practitioner Surveillance Network (SPSN) assessed interim 2015/16 vaccine effectiveness (VE) against influenza A(H1N1)pdm09 viruses. Adjusted VE showed significant protection of 64% (95% confidence interval (CI): 44–77%) overall and 56% (95%CI: 26–73%) for adults between 20 and 64 years-old against medically attended, laboratory-confirmed A(H1N1)pdm09 illness. Among the 67 A(H1N1)pdm09-positive specimens that were successfully sequenced, 62 (> 90%) belonged to the emerging genetic 6B.1 subclade, defined by S162N (potential gain of glycosylation) and I216T mutations in the haemagglutinin protein. Findings from the Canadian SPSN indicate that the 2015/16 northern hemisphere vaccine provided significant protection against A(H1N1)pdm09 illness despite genetic evolution in circulating viruses.

Background. Cases of infection due to a novel swine-origin variant of influenza A virus subtype H3N2 (H3N2v) have recently been identified in the United States, primarily among children. We estimate levels of cross-reactive antibody to H3N2v by age and assess whether seasonal trivalent inactivated influenza vaccine (TIV), with or without adjuvant, may increase seroprotection. Methods. Antibody to H3N2v was assessed by hemagglutination inhibition (HI) assay and, for a subset, also by microneutralization assay. Seroprevalence and seroprotection were defined as an HI titer of ≥40, and levels were compared with those for ancestral and contemporary human strains. The analysis included 1116 sera collected during fall 2010, corresponding to approximately 100 sera per decade of life. Vaccine-induced antibody levels were also assessed in sera from 136 children aged

Background. During the 2010–2011 winter, a large number of outbreaks due to influenza A/H3N2 at longterm care facilities, including higher-than-expected attack rates among vaccinated staff, were reported in some regions of Canada. Interim analysis from the community-based sentinel surveillance system showed circulating H3N2 variants and suboptimal vaccine effectiveness (VE), assessed here for the entire season’s data set. Methods. Nasal/nasopharyngeal swabs and epidemiologic details were collected from patients presenting to sentinel sites within 7 days of onset of influenza-like illness. Cases tested positive for influenza by real-time reverse-transcription polymerase chain reaction; controls tested negative. Odds ratios for medically attended, laboratory-confirmed influenza in vaccinated vs nonvaccinated participants were used to derive adjusted VE. Viruses were characterized by hemagglutination inhibition (HI), and the hemagglutinin genes of a subset were sequenced to explore vaccine relatedness. Results. Final 2010–2011 VE analysis included 1718 participants (half aged 20–49 years), 93 with A(H1N1) pdm09, 408 with A/H3N2, and 199 with influenza B. Among adults aged 20–49 years, adjusted VE was 65% (95% confidence interval [CI], 8%–87%) for A(H1N1)pdm09 and 66% (95% CI, 10%–87%) for influenza B. Vaccine effectiveness was substantially lower for A/H3N2, at 39% (95% CI, 0%–63%). Phylogenetic analysis identified 2 circulating H3N2 variant clades, A/HongKong/2121/2010 (87%) and A/Victoria/208/2009 (11%), bearing multiple amino acid substitutions at antigenic sites (12 and 8, respectively) compared with the H3N2 vaccine component used in Canada (A/Victoria/210/2009[NYMC X-187]). However, HI characterized all H3N2 isolates as well matched to the vaccine. Conclusions. Public health observations of increased facility H3N2 outbreaks were consistent with the sentinel network’s detection of genetic variants and suboptimal VE but not with conventional HI characterization. We highlight the utilityof a multicomponent sentinel surveillance platform that incorporates genotypic, phenotypic, and epidemiologic indicators into the assessment of influenza virus, new variant circulation, vaccine relatedness, and VE.

Trivalent inactivated influenza vaccine (TIV) contains 1 of 2 influenza B/lineages (B/Yamagata or B/Victoria) annually. We assessed prime-boost responses in young children following a change in the B/lineage included in TIV.Participants were primed during a clinical trial as infants or toddlers with two 0.25 or two 0.5 mL doses of 2008-2009 TIV containing B/Florida/4/06(Yamagata) antigen. In subsequent years, sequential subsets received annual age-appropriate doses of 2009-2010 and 2010-2011 TIV containing the changed influenza B/lineage antigen (B/Brisbane/60/08(Victoria)). Serologic response was assessed pre- and postimmunization by hemagglutination inhibition (HI; with/without ether treatment of influenza B antigen) and microneutralization. The primary immunogenicity outcome was the seroprotection rate (SPR) measured by HI without ether treatment (SPR:HI titers ≥40).Fifty-six children were included in 2009-2010 and 36 in 2010-2011 analyses. Before the 2009-2010 TIV dose, antibody to all 2008-2009 TIV components had fallen to low levels: SPR10% for B/Florida/4/06(Yamagata) and B/Brisbane/60/08(Victoria) antigens. A single 2009-2010 TIV dose boosted antibody to the shared 2008-2009/2009-2010 influenza A antigens and to the priming 2008-2009 B/Florida/4/06(Yamagata) antigen with SPRs85%. In contrast, antibody to the B/Brisbane/60/08(Victoria) antigen included in the 2009-2010 TIV remained low: SPR25%. Antibody to the B/Brisbane/60/08(Victoria) antigen was not improved from a further dose in the 2010-2011 TIV: SPR 31% versus SPR 69% to B/Yamagata. A similar pattern of B/Yamagata dominance was observed when HI testing was conducted with antigen prepared by ether treatment.Repeated annual TIV doses containing B/Victoria-lineage antigen strongly recalled antibodies to the B/Yamagata antigen of first exposure, but elicited lower B/Victoria responses.

OBJECTIVES: We assessed whether 2 full versus 2 half-doses of trivalent inactivated influenza vaccine (TIV) could improve immunogenicity without increasing reactogenicity in infants (aged 6–11 months) and toddlers (aged 12–23 months). METHODS: Previously unimmunized infants and toddlers were separately randomly assigned to receive 2 full (0.5-mL) or 2 half (0.25-mL) doses of 2008–2009 split TIV. Sera were collected at enrollment and at 27 to 45 days after the second injection. Parents recorded adverse events after each injection. The primary immunogenicity outcome was superiority (1-sided, α = 0.025) of the full versus the half-dose based on a >10% increase in rates of seroprotection (hemagglutination inhibition titer of ≥40). The primary reactogenicity outcome was fever of ≥38°C within 3 days of either injection. RESULTS: In per-protocol analyses, 252 participants (full dose: n = 124; half-dose: n = 128) were included. In toddlers, postimmunization seroprotection rates exceeded 85% for all 3 vaccine components without significant difference by dose. In infants, the full dose induced higher responses for all 3 vaccine components, meeting the 10% test of superiority for the H3N2 (75.4% vs 47.6%; Δ = 27.8% [95% confidence interval (CI): 11.2–44.5]; P = .02) and B/Yamagata (70.2% vs 41.3%; Δ = 28.9% [95% CI: 11.9–45.9]; P = .02) components but not H1N1 (71.9% vs 54.0%; Δ = 18.0% [95% CI: 1.0–34.9]; P = .2). Rates of fever were not increased among full- versus half-dose recipients in either age group (5.6% vs 12.7% combined). CONCLUSIONS: Administration of 2 full TIV doses may improve immunogenicity without increasing reactogenicity in infants. Current TIV dosing recommendations for young children warrant additional evaluation.

Background. In April 2009, an elementary school outbreak of pandemic H1N1 (pH1N1) influenza was reported in a community in northern British Columbia, Canada-an area that includes both non-Aboriginal and Aboriginal residents living on or off a reserve. During the outbreak investigation, we explored the relationship between prior receipt of trivalent inactivated influenza vaccine (TIV) and pH1N1-related illness. Methods. A telephone survey was conducted from 15 May through 5 June 2009 among households of children attending any school in the affected community. Members of participating households where influenza-like illness (ILI) was described were then invited to submit blood samples for confirmation of pH1N1 infection by hemagglutination inhibition and microneutralization assays. Circulation of pH1N1 was concentrated among households of the elementary school and elsewhere on-reserve to which analyses of TIV effect were thus restricted. Odds ratios (ORs) for the TIV effect on ILI were computed through logistic regression, with adjustment for age, comorbidity, household density, and Aboriginal status. The influence of within-household clustering was assessed through generalized-linear-mixed models. Results. Of 408 participants, 92 (23%) met ILI criteria: 29 (32%) of 92 persons with ILI, compared with 61 (19%) 316 persons without ILI, had received the 2008–2009 formulation of TIV. Fully adjusted ORs for 2008- 2009 TIV effect on ILI were 2.45 (95% confidence interval, 1.34–4.48) by logistic regression and 2.68 [95% confidence interval, 1.37–5.25) by generalized-linear-mixed model. Conclusions. An outbreak investigation in British Columbia during the late spring of 2009 provided the first indication of an unexpected association between receipt of TIV and pH1N1 illness. This led to 5 additional studies through the summer 2009 in Canada, each of which corroborated these initial findings.

Using an integrated surveillance platform, we incorporated genetic, antigenic, and epidemiologic indicators to evaluate agent–host factors that contributed to low vaccine effectiveness during the 2014–2015 influenza season, including variation in the viral genome and negative effects of serial vaccination., Background. The 2014–2015 influenza season was distinguished by an epidemic of antigenically-drifted A(H3N2) viruses and vaccine components identical to 2013–2014. We report 2014–2015 vaccine effectiveness (VE) from Canada and explore contributing agent–host factors. Methods. VE against laboratory-confirmed influenza was derived using a test-negative design among outpatients with influenza-like illness. Sequencing identified amino acid mutations at key antigenic sites of the viral hemagglutinin protein. Results. Overall, 815/1930 (42%) patients tested influenza-positive: 590 (72%) influenza A and 226 (28%) influenza B. Most influenza A viruses with known subtype were A(H3N2) (570/577; 99%); 409/460 (89%) sequenced viruses belonged to genetic clade 3C.2a and 39/460 (8%) to clade 3C.3b. Dominant clade 3C.2a viruses bore the pivotal mutations F159Y (a cluster-transition position) and K160T (a predicted gain of glycosylation) compared to the mismatched clade 3C.1 vaccine. VE against A(H3N2) was −17% (95% confidence interval [CI], −50% to 9%) overall with clade-specific VE of −13% (95% CI, −51% to 15%) for clade 3C.2a but 52% (95% CI, −17% to 80%) for clade 3C.3b. VE against A(H3N2) was 53% (95% CI, 10% to 75%) for patients vaccinated in 2014-2015 only, significantly lower at −32% (95% CI, −75% to 0%) if also vaccinated in 2013–2014 and −54% (95% CI, −108% to −14%) if vaccinated each year since 2012–2013. VE against clade-mismatched B(Yamagata) viruses was 42% (95% CI, 10% to 62%) with less-pronounced reduction from prior vaccination compared to A(H3N2). Conclusions. Variation in the viral genome and negative effects of serial vaccination likely contributed to poor influenza vaccine performance in 2014–2015.

As elsewhere, few (

Respiratory specimens collected from outpatients with influenza-like illness in three Canadian provinces (British Columbia (BC), Alberta and Quebec) participating in a community-based sentinel surveillance network were prospectively screened for enterovirus-D68 (EV-D68) from 1 August to 31 December 2014 and compared to specimens collected from 1 October 2013 to 31 July 2014. Eighteen (1%) of 1,894 specimens were EV-D68-positive: 1/348 (0.3%) collected from October to December 2013 and 11/460 (2.4%) from October to December 2014, an eight-fold increase in detection rates (p=0.01), consistent with epidemic circulation in autumn 2014. The remaining EV-D68 detections were in September 2014 (6/37). Enhanced passive surveillance was also conducted on all inpatient and outpatient EV-D68 cases (n=211) detected at the BC provincial reference laboratory from 28 August to 31 December 2014. Incidence of hospitalisations was 3/100,000 overall and 21, 17, 4 and 1/100,000 among those 1 among paediatric but not adult cases. Three cases in BC with comorbidity or co-infection died and five exhibited neurological features persisting >9 months. Active surveillance in outpatient and inpatient settings is needed from more areas and additional seasons to better understand EV-D68 epidemiology and potential at-risk groups for severe or unusual manifestations.

Objectives. To estimate influenza vaccine effectiveness (VE) for the 2007–2008 season and assess the sentinel surveillance system in Canada for monitoring virus evolution and impact on VE. Methods. Nasal/nasopharyngeal swabs and epidemiologic details were collected from patients presenting to a sentinel physician within 7 days of influenza-like illness onset. Cases tested positive for influenza A/B virus by real-time polymerase chain reaction; controls tested negative. Hemagglutination inhibition (HI) and gene sequencing explored virus relatedness to vaccine. VE was calculated as 1 minus the odds ratio for influenza in vaccinated versus nonvaccinated participants, with adjustment for confounders. Results. Of 1425 participants, 21% were vaccinated. Influenza virus was detected in 689 (48%), of which isolates from 663 were typed/subtyped: 189 (29%) were A/H1, 210 (32%) were A/H3, and 264 (40%) were B. Of A/H1N1 isolates, 6% showed minor HI antigenic mismatch to vaccine, with greater variation based on genetic identity. All A/H3N2 isolates showed moderate antigenic mismatch, and 98% of influenza B virus isolates showed major lineage-level mismatch to vaccine. Adjusted VE for A/H1N1, A/H3N2, and B components was 69% (95% confidence interval [CI], 44%–83%), 57% (95% CI, 32%–73%), and 55% (95% CI, 32%–70%), respectively, with an overall VE of 60% (95% CI, 45%–71%). Conclusions. Detailed antigenic and genotypic analysis of influenza viruses was consistent with epidemiologic estimates of VE showing cross-protection. A routine sentinel surveillance system that combines detailed virus and VE monitoring annually, as modeled in Canada, may guide improved vaccine selection and protection.

Background. Pandemic H1N1 (pH1N1) surveillance data showed lower attack rates but higher risk of severe outcomes with advanced age. We explored immuno-epidemiologic correlates of surveillance findings including humoral and cell-mediated immunity (CMI). Methods. In an age-based design, ∼100 banked/residual sera per 10-year age stratum were assessed by hemagglutination inhibition (HI) and microneutralization (MN) assays for preexisting antibody to pH1N1 and recent seasonal H1N1 and H3N2 strains. In a separate birth cohort design defined by childhood influenza A/subtype priming (1919–1929: H1N1; 1945–1949: H1N1; 1958–1960: H2N2; 1969–1970: H3N2; 1978–1989: H3N2/H1N1), whole blood was collected from up to 50 volunteers per birth cohort. The ratio of Th1(IFN-γ):Th2(IL-10) cytokine responses was evaluated in vitro. Results. Antibody to seasonal viruses was highest in school-age children. Cross-reactive HI/MN antibody to pH1N1 was low among participants

Background: Before pandemic (H1N1) 2009, less than 10% of serum samples collected from all age groups in the Lower Mainland of British Columbia, Canada, showed seroprotection against the pandemic (H1N1) 2009 virus, except those from very elderly people. We reassessed this profile of seroprotection by age in the same region six months after the fall 2009 pandemic and vaccination campaign. Methods: We evaluated 100 anonymized serum samples per 10-year age group based on convenience sampling. We measured levels of antibody against the pandemic virus by hemagglutination inhibition and microneutralization assays. We assessed geometric mean titres and the proportion of people with seroprotective antibody levels (hemagglutination inhibition titre ≥ 40). We performed sensitivity analyses to evaluate titre thresholds of 80, 20 and 10. Results: Serum samples from 1127 people aged 9 months to 101 years were obtained. The overall age-standardized proportion of people with seroprotective antibody levels was 46%. A U-shaped age distribution was identified regardless of assay or titre threshold applied. Among those less than 20 years old and those 80 years and older, the prevalence of seroprotection was comparably high at about 70%. Seroprotection was 44% among those aged 20–49 and 30% among those 50–79 years. It was lowest among people aged 70–79 years (21%) and highest among those 90 years and older (88%). Interpretation: We measured much higher levels of seroprotection after the 2009 pandemic compared than before the pandemic, with a U-shaped age distribution now evident. These findings, particularly the low levels of seroprotection among people aged 50–79 years, should be confirmed in other settings and closer to the influenza season.