scholarly journals Challenges of Making Effective Influenza Vaccines

2020 ◽  
Vol 7 (1) ◽  
pp. 495-512
Author(s):  
Sigrid Gouma ◽  
Elizabeth M. Anderson ◽  
Scott E. Hensley
Keyword(s):  
Influenza Vaccine ◽  
Seasonal Influenza ◽  
Influenza Season ◽  
Viral Evolution ◽  
Influenza Vaccines ◽  
Antigen Production ◽  
Production Processes ◽  
Vaccine Antigens ◽  
History Of ◽  
Viral Vaccines

Seasonal influenza vaccines prevent influenza-related illnesses, hospitalizations, and deaths. However, these vaccines are not as effective as other viral vaccines, and there is clearly room for improvement. Here, we review the history of seasonal influenza vaccines, describe challenges associated with producing influenza vaccine antigens, and discuss the inherent difficulties of updating influenza vaccine strains each influenza season. We argue that seasonal influenza vaccines can be dramatically improved by modernizing antigen production processes and developing models that are better at predicting viral evolution. Resources should be specifically dedicated to improving seasonal influenza vaccines while developing entirely new vaccine platforms.

scholarly journals Rapid assessment of influenza vaccine effectiveness: analysis of an internet-based cohort

2011 ◽  
Vol 140 (7) ◽  
pp. 1309-1315 ◽  
Author(s):  
K. T. D. EAMES ◽  
E. BROOKS-POLLOCK ◽  
D. PAOLOTTI ◽  
M. PEROSA ◽  
C. GIOANNINI ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Pandemic Influenza ◽  
Seasonal Influenza ◽  
Influenza Season ◽  
Rapid Assessment ◽  
Vaccine Effectiveness ◽  
Influenza Vaccines ◽  
Seasonal Influenza Vaccine ◽  
Effectiveness Analysis ◽  
Self Reports

SUMMARYThe effectiveness of influenza vaccination programmes is seldom known during an epidemic. We developed an internet-based system to record influenza-like symptoms and response to infection in a participating cohort. Using self-reports of influenza-like symptoms and of influenza vaccine history and uptake, we estimated vaccine effectiveness (VE) without the need for individuals to seek healthcare. We found that vaccination with the 2010 seasonal influenza vaccine was significantly protective against influenza-like illness (ILI) during the 2010–2011 influenza season (VE 52%, 95% CI 27–68). VE for individuals who received both the 2010 seasonal and 2009 pandemic influenza vaccines was 59% (95% CI 27–77), slightly higher than VE for those vaccinated in 2010 alone (VE 46%, 95% CI 9–68). Vaccinated individuals with ILI reported taking less time off work than unvaccinated individuals with ILI (3·4 days vs. 5·3 days, P<0·001).

scholarly journals Healthcare Workers’ Perspectives on the Upcoming COVID-19 Vaccine in Terms of Their Exposure to the Influenza Vaccine in Riyadh, Saudi Arabia: A Cross-Sectional Study

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 465
Author(s):  
Leena R. Baghdadi ◽  
Shatha G. Alghaihb ◽  
Alanoud A. Abuhaimed ◽  
Dania M. Alkelabi ◽  
Rawan S. Alqahtani
Keyword(s):  
Saudi Arabia ◽  
Influenza Vaccine ◽  
Work Experience ◽  
Healthcare Workers ◽  
Seasonal Influenza ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Seasonal Influenza Vaccine ◽  
History Of

In 2019, a novel severe acute respiratory syndrome (SARS-CoV-2 (COVID-19)) caused a global pandemic. There was an urgent need to develop a vaccine against COVID-19 to reduce its spread and economic burden. The main objective of this study was to understand the attitudes and concerns of healthcare workers (HCWs) towards the upcoming COVID-19 vaccine, whether their decision was influenced by their history of taking the seasonal influenza vaccine, and factors that influence the acceptance of the upcoming COVID-19 vaccine. This was a cross-sectional study conducted in Riyadh, Saudi Arabia. We selected and surveyed 356 HCWs via an electronic self-administered questionnaire. A total of 61.16% of HCWs were willing to receive the COVID-19 vaccine, and 55.9% of them had received the seasonal influenza vaccine in the preceding year (2019–2020). The strongest predictors for taking the COVID-19 vaccine were the HCWs’ belief that the COVID-19 vaccine would be safe, needed even for healthy people, that all HCWs should be vaccinated against COVID-19, and that HCWs will have time to take the vaccine. Being female, being middle aged, having <5 years of work experience, having no fear of injections, and being a non-smoker were predictive factors for taking the upcoming COVID-19 vaccine. No associations were found between the intention to take the COVID-19 vaccine and a history of taking the seasonal influenza vaccine.

scholarly journals An Antigenic Thrift-Based Approach to Influenza Vaccine Design

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 657
Author(s):  
Jai S. Bolton ◽  
Hannah Klim ◽  
Judith Wellens ◽  
Matthew Edmans ◽  
Uri Obolski ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Influenza Season ◽  
Vaccine Design ◽  
Antigenic Drift ◽  
Influenza Vaccines ◽  
Immune Protection ◽  
Immune Selection ◽  
Drift Theory ◽  
Gradual Accumulation ◽  
Additional Constraints

The antigenic drift theory states that influenza evolves via the gradual accumulation of mutations, decreasing a host’s immune protection against previous strains. Influenza vaccines are designed accordingly, under the premise of antigenic drift. However, a paradox exists at the centre of influenza research. If influenza evolved primarily through mutation in multiple epitopes, multiple influenza strains should co-circulate. Such a multitude of strains would render influenza vaccines quickly inefficacious. Instead, a single or limited number of strains dominate circulation each influenza season. Unless additional constraints are placed on the evolution of influenza, antigenic drift does not adequately explain these observations. Here, we explore the constraints placed on antigenic drift and a competing theory of influenza evolution – antigenic thrift. In contrast to antigenic drift, antigenic thrift states that immune selection targets epitopes of limited variability, which constrain the variability of the virus. We explain the implications of antigenic drift and antigenic thrift and explore their current and potential uses in the context of influenza vaccine design.

Relative Effectiveness of Cell-Cultured versus Egg-Based Seasonal Influenza Vaccines in Preventing Influenza-Related Outcomes in Subjects 18 Years Old or Older: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Joan Puig-Barberà ◽  
Sonia Tamames-Gómez ◽  
Pedro Plans-Rubio ◽  
José María Eirós-Bouza
Keyword(s):  
Systematic Review ◽  
Seasonal Influenza ◽  
Influenza Season ◽  
Meta Analysis ◽  
Relative Effectiveness ◽  
Risk Of Bias ◽  
Influenza Vaccines ◽  
Sensitivity Analyses ◽  
Exclusion Criteria ◽  
Seed Cell

Avian mutations in vaccine strains obtained from embryonated eggs could impair vaccine effec-tiveness. We performed a systematic review and meta-analysis of the adjusted relative vaccine effectiveness (arVE) of seed cell-cultured influenza vaccines (ccIV) compared to egg-based influ-enza vaccines (eIV) in preventing laboratory-confirmed influenza related outcomes (IRO) or IRO by clinical codes, in subjects 18 and over. We completed the literature search in January 2021; ap-plied exclusion criteria, evaluated risk of bias of the evidence, and performed heterogeneity, pub-lication bias, qualitative, quantitative and sensitivity analyses. All estimates were computed us-ing a random approach. International Prospective Register of Systematic Reviews, CRD42021228290. We identified 12 publications that reported 26 adjusted arVE results. Five publications reported 13 laboratory confirmed arVE and seven reported 13 code-ascertained arVE. Nine publications with 22 results were at low risk of bias. Heterogeneity was explained by season and risk of bias. We found a significant 11% (8 to 14%) adjusted arVE favoring ccIV in preventing any IRO in the 2017-2018 influenza season. The arVE was 3% (-01 to 7%) in the 2018-2019 influenza season. We found moderate evidence of a significant advantage of the ccIV in preventing IRO, compared to eIV, in a well-matched A(H3N2) predominant season.

scholarly journals Relative Effectiveness of the Cell-Cultured Quadrivalent Influenza Vaccine Compared to Standard, Egg-derived Quadrivalent Influenza Vaccines in Preventing Influenza-like Illness in 2017–2018

2020 ◽  
Vol 71 (10) ◽  
pp. e665-e671 ◽  
Author(s):  
Constantina Boikos ◽  
Gregg C Sylvester ◽  
John S Sampalis ◽  
James A Mansi
Keyword(s):  
Cell Culture ◽  
Health Status ◽  
Influenza Vaccine ◽  
Influenza Season ◽  
Relative Effectiveness ◽  
Geographic Region ◽  
Influenza Vaccines ◽  
Study Cohort ◽  
Influenza Like Illness ◽  
Adaptive Mutations

Abstract Background Influenza antigens may undergo adaptive mutations during egg-based vaccine production. In the 2017–2018 influenza season, quadrivalent, inactivated cell-derived influenza vaccine (ccIIV4) vaccine was produced using A(H3N2) seed virus propagated exclusively in cell culture, thus lacking egg adaptive changes. This United States study estimated relative vaccine effectiveness (rVE) of ccIIV4 vs egg-derived quadrivalent vaccines (egg-derived IIV4) for that season. Methods Vaccination, outcome, and covariate data were ascertained retrospectively from a electronic medical record (EMR) dataset and analyzed. The study cohort included patients ≥ 4 years of age. rVE was estimated against influenza-like illness (ILI) using diagnostic International Classification of Diseases, Ninth or Tenth Revision codes. The adjusted odds ratios used to derive rVE estimates were estimated from multivariable logistic regression models adjusted for age, sex, race/ethnicity, geographic region, and health status. Results Overall, 92 187 individuals had a primary care EMR record of ccIIV4 and 1 261 675 had a record of egg-derived IIV4. In the ccIIV4 group, 1705 narrowly defined ILI events occurred, and 25 645 occurred in the standard egg-derived IIV4 group. Crude rVE was 9.2% (95% confidence interval [CI], 4.6%–13.6%). When adjusted for age, sex, health status, comorbidities, and geographic region, the estimated rVE changed to 36.2% (95% CI, 26.1%–44.9%). Conclusions ccIIV4, derived from A(H3N2) seed virus propagated exclusively in cell culture, was more effective than egg-derived IIV4 in preventing ILI during the 2017–2018 influenza season. This result suggests that cell-derived influenza vaccines may have greater effectiveness than standard egg-derived vaccines.

scholarly journals Influenza Vaccine Match with Circulating Strains and Indicators of Influenza Strain Impact - Canada 1980 to 1992

1998 ◽  
Vol 9 (3) ◽  
pp. 143-148 ◽  
Author(s):  
Edward Ellis ◽  
John M Weber ◽  
Wilf Cuff ◽  
Susan G Mackenzie
Keyword(s):  
Influenza Vaccine ◽  
Ecological Study ◽  
Influenza Season ◽  
National Laboratory ◽  
Mortality Rates ◽  
Mortality Data ◽  
Influenza Strain ◽  
Previous Season ◽  
Vaccine Antigens ◽  
Excess Deaths

OBJECTIVES: To determine the similarity between influenza vaccine antigens and viruses associated with laboratory-confirmed infections by virus type/subtype, strain and influenza season; to correlate pneumonia and influenza hospitalization and mortality rates with the number of laboratory-confirmed influenza infections in an influenza season; and to develop predictive indicators of the likely incidence of current strains in the following season.DESIGN: Ecological study using national laboratory, pneumonia and influenza hospitalization and mortality data.SETTING: Canada, influenza seasons from 1980 to 1992.POPULATION STUDIED: Individuals with laboratory-confirmed influenza infections, pneumonia and influenza hospitalizations or deaths.INTERVENTION: Influenza immunization.MAIN RESULTS: Similarity of circulating strains and vaccine antigens was 99% for A(H1N1), 65% for A(H3N2) and 65% for B strains. During outbreaks, pneumonia and influenza hospitalization, and mortality rates increased 19% or less and 21% or less for A(H1N1), respectively; 28% or less and 51% or less for A(H3N2), and 19% or less and 16% or less for B strains. There were usually fewer than 25 laboratory-confirmed A(H1N1) infections with a particular strain in a season if there had been more than 25 infections with similar strains the previous season. For A(H3N2), the figure was 100, and for B it was 150.CONCLUSIONS: Matches were excellent for A(H1N1) and good for A(H3N2) plus B strains. Hospitalization and mortality rates increased substantially during outbreaks, eg, estimated 1609 excess deaths during a widespread A(H3N2) outbreak. This study identifies relationships that provide some ability to predict the incidence of a particular influenza strain in a coming season based on the incidence of strains similar to it in the previous season.

scholarly journals A Real-World Clinical and Economic Analysis of Cell-derived Quadrivalent Influenza Vaccine Compared to Standard Egg-derived Quadrivalent Influenza Vaccines During the 2019-20 Influenza Season in the United States

2021 ◽  
Author(s):  
Victoria Divino ◽  
Vamshi Ruthwik Anupindi ◽  
Mitch DeKoven ◽  
Joaquin Mould-Quevedo ◽  
Stephen I Pelton ◽  
...  
Keyword(s):  
High Risk ◽  
Influenza Vaccine ◽  
Influenza Season ◽  
The United States ◽  
Vaccine Effectiveness ◽  
Influenza Vaccines ◽  
Sensitivity Analyses ◽  
Administrative Claims ◽  
Adaptive Mutations ◽  
Quadrivalent Influenza Vaccine

Abstract Background Cell-derived influenza vaccines are not subject to egg adaptive mutations that have potential to decrease vaccine effectiveness. This retrospective analysis estimated the relative vaccine effectiveness (rVE) of cell-derived quadrivalent influenza vaccine (IIV4c) compared to standard egg-derived quadrivalent influenza vaccines (IIV4e) among recipients aged 4-64 years in the US during the 2019-20 influenza season. Methods The IQVIA PharMetrics® Plus administrative claims database was utilized. Study outcomes were assessed post-vaccination through the end of the study period (March 7, 2020). Inverse probability of treatment weighting (IPTW) was implemented to adjust for covariate imbalance. Adjusted rVE against influenza-related hospitalizations/emergency room (ER) visits and other clinical outcomes was estimated through IPTW-weighted Poisson regression models for the IIV4c and IIV4e cohorts and for the subgroup with ≥1 high-risk condition. Sensitivity analyses modifying the outcome assessment period as well as a doubly-robust analysis were also conducted. IPTW-weighted generalized linear models were used to estimate predicted annualized all-cause costs. Results The final sample comprised 1,138,969 IIV4c and 3,926,357 IIV4e recipients following IPTW adjustment. IIV4c was more effective in preventing influenza-related hospitalizations/ER visits as well as respiratory-related hospitalizations/ER visits compared to IIV4e. IIV4c was also more effective for the high-risk subgroup and across the sensitivity analyses. IIV4c was also associated with significantly lower annualized all-cause total costs compared to IIV4e (-$467), driven by lower costs for outpatient medical services and inpatient hospitalizations. Conclusions IIV4c was significantly more effective in preventing influenza-related hospitalizations/ER visits compared to IIV4e and was associated with significantly lower all-cause costs.

scholarly journals Allergic adverse events following 2015 seasonal influenza vaccine, Victoria, Australia

2017 ◽  
Vol 22 (20) ◽  
Author(s):  
Hazel J Clothier ◽  
Nigel Crawford ◽  
Melissa A Russell ◽  
Jim P Buttery
Keyword(s):  
Adverse Events ◽  
Confidence Interval ◽  
Influenza Vaccine ◽  
Allergic Reaction ◽  
Seasonal Influenza ◽  
Vaccine Safety ◽  
Clinical Severity ◽  
Influenza Vaccines ◽  
Seasonal Influenza Vaccine ◽  
Initial Investigation

Australia was alerted to a possible increase in allergy-related adverse events following immunisation (AEFI) with 2015 seasonal trivalent influenza vaccines (TIV) by the Victorian state vaccine safety service, SAEFVIC. We describe SAEFVIC’s initial investigation and upon conclusion of the 2015 influenza vaccination programme, to define the signal event and implications for vaccine programmes. Allergy-related AEFI were defined as anaphylaxis, angioedema, urticaria or generalised allergic reaction. Investigations compared 2015 TIV AEFI reports to previous years as proportions and reporting risk (RR) per 100,000, stratified by influenza vaccine brand. The initial investigation showed an increased proportion of allergy-related AEFI compared with 2014 (25% vs 12%), predominantly in adults, with insufficient clinical severity to alter the programme risk-benefit. While overall TIV AEFI RR in 2015 was similar to previous years (RR: 1.07, 95% confidence interval (CI): 0.88–1.29), we identified a near-doubling RR for allergy-related AEFI in 2015 (RR: 1.78, 95% CI: 1.14­– 2.80) from 2011 to 2014 with no difference by vaccine brand or severity increase identified. This increase in generalised allergy-related AEFI, across all used vaccine brands, supports evidence of variable reactogenicity arising from influenza vaccine strain variations. This investigation underlines the importance of effective seasonal influenza vaccine pharmacovigilance.

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