BackgroundInfluenza vaccine effectiveness (VE) is generally interpreted in the context of vaccine match/mismatch to circulating strains with evolutionary drift in the latter invoked to explain reduced protection. During the 2012–13 season, however, detailed genotypic and phenotypic characterization shows that low VE was instead related to mutations in the egg-adapted H3N2 vaccine strain rather than antigenic drift in circulating viruses.Methods/FindingsComponent-specific VE against medically-attended, PCR-confirmed influenza was estimated in Canada by test-negative case-control design. Influenza A viruses were characterized genotypically by amino acid (AA) sequencing of established haemagglutinin (HA) antigenic sites and phenotypically through haemagglutination inhibition (HI) assay. H3N2 viruses were characterized in relation to the WHO-recommended, cell-passaged vaccine prototype (A/Victoria/361/2011) as well as the egg-adapted strain as per actually used in vaccine production. Among the total of 1501 participants, influenza virus was detected in 652 (43%). Nearly two-thirds of viruses typed/subtyped were A(H3N2) (394/626; 63%); the remainder were A(H1N1)pdm09 (79/626; 13%), B/Yamagata (98/626; 16%) or B/Victoria (54/626; 9%). Suboptimal VE of 50% (95%CI: 33–63%) overall was driven by predominant H3N2 activity for which VE was 41% (95%CI: 17–59%). All H3N2 field isolates were HI-characterized as well-matched to the WHO-recommended A/Victoria/361/2011 prototype whereas all but one were antigenically distinct from the egg-adapted strain as per actually used in vaccine production. The egg-adapted strain was itself antigenically distinct from the WHO-recommended prototype, and bore three AA mutations at antigenic sites B [H156Q, G186V] and D [S219Y]. Conversely, circulating viruses were identical to the WHO-recommended prototype at these positions with other genetic variation that did not affect antigenicity. VE was 59% (95%CI:16–80%) against A(H1N1)pdm09, 67% (95%CI: 30–85%) against B/Yamagata (vaccine-lineage) and 75% (95%CI: 29–91%) against B/Victoria (non-vaccine-lineage) viruses.ConclusionsThese findings underscore the need to monitor vaccine viruses as well as circulating strains to explain vaccine performance. Evolutionary drift in circulating viruses cannot be regulated, but influential mutations introduced as part of egg-based vaccine production may be amenable to improvements.

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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.

Failure of passive transfer of immunity (FPT) in dairy replacement calves has been linked to increased neonatal morbidity and mortality and long-term decreases in productivity. The purpose of this study was to estimate the prevalence of FPT in US dairy heifer calves in 2007 and to use nationally representative data to investigate associations of FPT with colostrum and calf management practices. A cross-sectional study was conducted by the USDA's National Animal Health Monitoring System between January and August 2007. Producers from 394 operations in 17 states completed survey questions about colostrum and calf management practices, and serum samples were collected from 1,816 healthy heifer calves on those operations. Serum immunoglobulin G (IgG) levels were determined by radial immunodiffusion, and calves were classified as having FPT if the IgG concentration was less than 10 mg/mL. To investigate associations between FPT and management practices, a multivariable analysis was completed using a weighted logistic regression model. The estimated prevalence of FPT in US dairy heifer calves was 19.2%. The odds of FPT were higher for calves on operations that pooled colostrum [odds ratio (OR = 2.2)], allowed nursing (OR = 2.4), or hand fed colostrum more than 4 h after birth (OR = 2.7). The odds of FPT were also higher for calves on operations that did not provide a source of heat during cold weather for calves experiencing a dystocia (OR = 1.6), would not seek veterinary assistance when unable to correctly position a calf for delivery (OR = 2.6), or did not routinely monitor serum proteins in calves as a measure of passive transfer (OR = 13.8). The prevalence of FPT in dairy heifer calves has decreased in the last 15 yr, so progress has been made in this important area of calf management. This study identified several management practices associated with FPT that could be targeted for educational campaigns or further research.

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.