Role of Egg-adaptation Mutations in Low Influenza A(H3N2) Vaccine Effectiveness During the 2012-2013 Season.
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SUBMITTER: Skowronski DM
PROVIDER: S-EPMC6186855 | biostudies-literature | 2018 Oct
REPOSITORIES: biostudies-literature
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Role of Egg-adaptation Mutations in Low Influenza A(H3N2) Vaccine Effectiveness During the 2012-2013 Season.
Skowronski Danuta M DM De Serres Gaston G
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20181001 9
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Project description:BackgroundInfluenza vaccination aims to prevent infection by influenza virus and reduce associated morbidity and mortality; however, vaccine effectiveness (VE) can be modest, especially for subtype A(H3N2). Low VE has been attributed to mismatches between the vaccine and circulating influenza strains and to the vaccine's elicitation of protective immunity in only a subset of the population. The low H3N2 VE in the 2012-2013 season was attributed to egg-adaptive mutations that created antigenic mismatch between the actual vaccine strain (IVR-165) and both the intended vaccine strain (A/Victoria/361/2011) and the predominant circulating strains (clades 3C.2 and 3C.3).MethodsWe investigated the basis of low VE in 2012-2013 by determining whether vaccinated and unvaccinated individuals were infected by different viral strains and by assessing the serologic responses to IVR-165, A/Victoria/361/2011, and 3C.2 and 3C.3 strains in an adult cohort before and after vaccination.ResultsWe found no significant genetic differences between the strains that infected vaccinated and unvaccinated individuals. Vaccination increased titers to A/Victoria/361/2011 and 3C.2 and 3C.3 representative strains as much as to IVR-165. These results are consistent with the hypothesis that vaccination boosted cross-reactive immune responses instead of specific responses against unique vaccine epitopes. Only approximately one-third of the cohort achieved a ≥4-fold increase in titer.ConclusionsIn contrast to analyses based on ferret studies, low H3N2 VE in 2012-2013 in adults does not appear to be due to egg adaptation of the vaccine strain. Instead, low VE might have been caused by low vaccine immunogenicity in a subset of the population.
| S-EPMC6051447 | biostudies-literature
Project description: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.
| S-EPMC3965421 | biostudies-literature
Project description:BACKGROUND:Since 2007, trivalent inactivated influenza vaccine has been provided free-of-charge to older adults aged ≥60 years in Beijing, China, but the data regarding influenza vaccine effectiveness (VE) among these people are very limited so far. We sought to estimate influenza VE against medically-attended laboratory-confirmed influenza illness among older adults during the 2013-2014 season. METHODS:The influenza-like illness (ILI) patients aged 60 years and older who participated in the influenza virological surveillance of Beijing during 2013-2014 influenza season were recruited in this study. A test-negative design was employed to estimate influenza VE among older adults by using logistic regression models. VE was estimated using logistic regression, adjusted for sex, age, interval (days) between illness onset and specimen collection, and week of illness onset. RESULTS:Between 1 November, 2013 and 30 April, 2014, a total of 487 elderly ILI patients were enrolled in the study, including 133 influenza-positive cases (of whom 6.8% were vaccinated) and 354 influenza-negative controls (of whom 10.2% were vaccinated). Among 133 influenza-positive cases, 51 tested positive for A(H1N1)pdm09 virus, 22 positive for A(H3N2) virus, 52 tested positive for B/Yamagata-lineage virus, 2 positive for B/Victoria-lineage virus, 1 positive for both A(H1N1)pdm09 and A(H3N2) viruses, and 5 tested positive for viruses of unknown subtype or lineage. The adjusted overall VE was estimated as 32% (95% CI:-48-69), with 59% (95% CI: -79-90) against A(H1N1)pdm09, 22% (95% CI: -253-83) against A(H3N2) and -20% (95% CI: -239-58) against B/Yamagata-lineage viruses. CONCLUSIONS:These results suggested a modest protective effect of the 2013-2014 influenza vaccine among older adults in Beijing which was not statistically significant, with higher VE against the A(H1N1)pdm09 viruses compared to A(H3N2) and B viruses.
| S-EPMC6037442 | biostudies-literature
Project description:BackgroundMost evidence of the effectiveness of influenza vaccines comes from studies conducted in primary care, but less is known about their effectiveness in preventing serious complications. Here, we examined the influenza vaccine effectiveness (IVE) against hospitalization with PCR-confirmed influenza in the predominant A(H3N2) 2011-2012 influenza season.MethodsA hospital-based, test-negative study was conducted in nine hospitals in Valencia, Spain. All emergency admissions with a predefined subset of symptoms were eligible. We enrolled consenting adults age 18 and over, targeted for influenza vaccination because of comorbidity, with symptoms of influenza-like-illness within seven days of admission. We estimated IVE as (1-adjusted vaccination odds ratio)*100 after accounting for major confounders, calendar time and recruitment hospital.ResultsThe subjects included 544 positive for influenza A(H3N2) and 1,370 negative for influenza admissions. Age was an IVE modifying factor. Regardless of vaccine administration, IVE was 72% (38 to 88%) in subjects aged under 65 and 21% (-5% to 40%) in subjects aged 65 and over. By type of vaccine, the IVE of classical intramuscular split-influenza vaccine, used in subjects 18 to 64, was 68% (12% to 88%). The IVE for intradermal and virosomal influenza vaccines, used in subjects aged 65 and over, was 39% (11% to 58%) and 16% (-39% to 49%), respectively.ConclusionsThe split-influenza vaccine was effective in preventing influenza-associated hospitalizations in adults aged under 65. The intradermal vaccine was moderately effective in those aged 65 and over.
| S-EPMC4230985 | biostudies-literature
Project description:Influenza A is a serious disease that causes significant morbidity and mortality, and vaccines against the seasonal influenza disease are of variable effectiveness. In this article, we discuss the use of the pepitope method to predict the dominant influenza strain and the expected vaccine effectiveness in the coming flu season. We illustrate how the effectiveness of the 2014/2015 A/Texas/50/2012 [clade 3C.1] vaccine against the A/California/02/2014 [clade 3C.3a] strain that emerged in the population can be estimated via pepitope In addition, we show by a multidimensional scaling analysis of data collected through 2014, the emergence of a new A/New Mexico/11/2014-like cluster [clade 3C.2a] that is immunologically distinct from the A/California/02/2014-like strains.
| S-EPMC4955871 | biostudies-literature
Project description:Here, we sequenced 10 influenza A(H3N2) virus genomes isolated from Finnish patients diagnosed with flu-like illness during the 2012-2013 influenza season. The alignment showed a high number of amino acid substitutions (238 in total) in only 10 samples, proving that a high mutation rate exists in seasonal influenza A viruses.
| S-EPMC3968323 | biostudies-literature
Project description:BackgroundWe compared effects of prior vaccination and added or lost protection from current season vaccination among those previously vaccinated.MethodsOur analysis included data from the US Flu Vaccine Effectiveness Network among participants ≥9 years old with acute respiratory illness from 2012-2013 through 2017-2018. Vaccine protection was estimated using multivariate logistic regression with an interaction term for effect of prior season vaccination on current season vaccine effectiveness. Models were adjusted for age, calendar time, high-risk status, site, and season for combined estimates. We estimated protection by combinations of current and prior vaccination compared to unvaccinated in both seasons or current vaccination among prior vaccinated.ResultsA total of 31 819 participants were included. Vaccine protection against any influenza averaged 42% (95% confidence interval [CI], 38%-47%) among those vaccinated only the current season, 37% (95% CI, 33-40) among those vaccinated both seasons, and 26% (95% CI, 18%-32%) among those vaccinated only the prior season, compared with participants vaccinated neither season. Current season vaccination reduced the odds of any influenza among patients unvaccinated the prior season by 42% (95% CI, 37%-46%), including 57%, 27%, and 55% against A(H1N1), A(H3N2), and influenza B, respectively. Among participants vaccinated the prior season, current season vaccination further reduced the odds of any influenza by 15% (95% CI, 7%-23%), including 29% against A(H1N1) and 26% against B viruses, but not against A(H3N2).ConclusionsOur findings support Advisory Committee on Immunization Practices recommendations for annual influenza vaccination. Benefits of current season vaccination varied among participants with and without prior season vaccination, by virus type/subtype and season.
| S-EPMC8326585 | biostudies-literature
Project description:Recently, we developed a seasonal influenza prediction system that uses an advanced data assimilation technique and real-time estimates of influenza incidence to optimize and initialize a population-based mathematical model of influenza transmission dynamics. This system was used to generate and evaluate retrospective forecasts of influenza peak timing in New York City. Here we present weekly forecasts of seasonal influenza developed and run in real time for 108 cities in the USA during the recent 2012-2013 season. Reliable ensemble forecasts of influenza outbreak peak timing with leads of up to 9 weeks were produced. Forecast accuracy increased as the season progressed, and the forecasts significantly outperformed alternate, analogue prediction methods. By week 52, prior to peak for the majority of cities, 63% of all ensemble forecasts were accurate. To our knowledge, this is the first time predictions of seasonal influenza have been made in real time and with demonstrated accuracy.
| S-EPMC3873365 | biostudies-literature
Project description:There is concern that influenza vaccine effectiveness (VE) may be attenuated by passage in eggs during manufacture. We compared quadrivalent cell-culture vaccine with egg-based vaccines, most of which were trivalent, against influenza A and B during 2017-2018 when A(H3N2) and B/Yamagata (present only in quadrivalent vaccines) predominated. We retrospectively examined risk of PCR-confirmed influenza A and B in members of Kaiser Permanente Northern California aged 4-64 years. We estimated the relative VE (rVE) of cell-culture vaccine versus egg-based vaccines, and the absolute VE (aVE) of each vaccine comparing vaccinated to unvaccinated individuals. Analyses used Cox regression with a calendar timeline, stratified by birth year, and adjusted for demographics, co-morbidities and utilization. One-third (1,016,965/3,053,248) of the population was vaccinated; 932,545 (91.7% of vaccinees) received egg-based and 84,420 (8.3%) received cell-culture vaccines. The rVE against influenza A was 8.0% (95% CI: -10, 23); aVE was 31.7% (CI: 18.7, 42.6) for cell-culture and 20.1% (CI: 14.5, 25.4) for egg-based vaccines. The rVE against influenza B was 39.6% (CI: 27.9, 49.3); aVE was 40.9% (CI: 30, 50.1) for cell-culture and 9.7% (CI 3.5, 15.6) for egg-based trivalent vaccines. Inclusion of the B/Yamagata lineage in the quadrivalent cell-based vaccine provided better protection against influenza B but vaccine effectiveness against influenza A was low for both the cell-culture vaccine and the egg-based vaccines. Improving influenza vaccines requires ongoing comparative vaccine effectiveness monitoring.
| S-EPMC7043803 | biostudies-literature
Project description:BackgroundThe effectiveness of currently licensed vaccines against influenza has not been clearly established, especially among individuals at increased risk for complications from influenza. We used a test-negative approach to estimate influenza vaccine effectiveness (IVE) against hospitalization with laboratory-confirmed influenza based on data collected from the Global Influenza Hospital Surveillance Network (GIHSN).Methods and findingsThis was a multi-center, prospective, active surveillance, hospital-based epidemiological study during the 2012-2013 influenza season. Data were collected from hospitals participating in the GIHSN, including five in Spain, five in France, and four in the Russian Federation. Influenza was confirmed by reverse transcription-polymerase chain reaction. IVE against hospitalization for laboratory-confirmed influenza was estimated for adult patients targeted for vaccination and who were swabbed within 7 days of symptom onset. The overall adjusted IVE was 33% (95% confidence interval [CI], 11% to 49%). Point estimates of IVE were 23% (95% CI, -26% to 53%) for influenza A(H1N1)pdm09, 30% (95% CI, -37% to 64%) for influenza A(H3N2), and 43% (95% CI, 17% to 60%) for influenza B/Yamagata. IVE estimates were similar in subjects <65 and ≥65 years of age (35% [95% CI, -15% to 63%] vs.31% [95% CI, 4% to 51%]). Heterogeneity in site-specific IVE estimates was high (I2 = 63.4%) for A(H1N1)pdm09 in patients ≥65 years of age. IVE estimates for influenza B/Yamagata were homogenous (I2 = 0.0%).ConclusionsThese results, which were based on data collected from the GIHSN during the 2012-2013 influenza season, showed that influenza vaccines provided low to moderate protection against hospital admission with laboratory-confirmed influenza in adults targeted for influenza vaccination. In this population, IVE estimates against A(H1N1)pdm09 were sensitive to age group and study site. Influenza vaccination was moderately effective in preventing admissions with influenza B/Yamagata for all sites and age groups.
| S-EPMC4063939 | biostudies-literature