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.

scholarly journals Strategies Targeting Hemagglutinin as a Universal Influenza Vaccine

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 257
Author(s):  
Brianna L. Bullard ◽  
Eric A. Weaver
Keyword(s):  
Influenza Virus ◽  
Influenza Vaccine ◽  
Vaccine Efficacy ◽  
Influenza Season ◽  
Surface Protein ◽  
Antigenic Drift ◽  
Influenza Vaccines ◽  
Viral Diversity ◽  
Universal Influenza Vaccine ◽  
Ha Protein

Influenza virus has significant viral diversity, both through antigenic drift and shift, which makes development of a vaccine challenging. Current influenza vaccines are updated yearly to include strains predicted to circulate in the upcoming influenza season, however this can lead to a mismatch which reduces vaccine efficacy. Several strategies targeting the most abundant and immunogenic surface protein of influenza, the hemagglutinin (HA) protein, have been explored. These strategies include stalk-directed, consensus-based, and computationally derived HA immunogens. In this review, we explore vaccine strategies which utilize novel antigen design of the HA protein to improve cross-reactive immunity for development of a universal influenza vaccine.

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 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 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 2753. Induction of Broadly Cross-Reactive Immune Responses Against A(H3N2) Airuses: Results of a Phase 2 Trial of a Novel Recombinant Hemagglutinin Saponin-Adjuvanted Nanoparticle Seasonal Influenza Vaccine

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S970-S970
Author(s):  
Vivek Shinde ◽  
Rongman Cai ◽  
Joyce S Plested ◽  
Bin Zhou ◽  
Haixia Zhou ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza Vaccine ◽  
Seasonal Influenza ◽  
Antibody Responses ◽  
Antigenic Drift ◽  
Influenza Vaccines ◽  
High Dose ◽  
Phase 2 ◽  
Adaptive Mutations ◽  
Phase 2 Trial

Abstract Background We developed a recombinant saponin-adjuvanted (Matrix-M1) quadrivalent hemagglutinin nanoparticle influenza vaccine (qNIV; NanoFlu) for older adults to address two impediments to efficacy of current, predominantly egg-derived, seasonal influenza vaccines: (1) limited protection against antigenic drift variants, particularly H3N2 viruses; and (2) antigenic mismatch between vaccine and circulating strains due to egg-adaptive mutations arising during manufacturing. In a prior Phase 1 trial, we showed that qNIV induced robust, broadly cross-reactive antibody responses against multiple antigenically drifted H3N2 viruses, which were 47–64% better than the egg-derived comparator trivalent high-dose inactivated influenza vaccine (IIV3-HD; Fluzone-High Dose). We undertook a Phase 2 trial to optimize the formulation of qNIV, and to compare qNIV immune responses to those of IIV3-HD and quadrivalent recombinant influenza vaccine (RIV4; FluBlok). Methods In this phase 2 dose and formulation finding RCT, we randomized 1,375 subjects aged ≥65 years to be immunized with 1 of 7 test vaccines: 5 different formulations of qNIV, IIV3-HD, or RIV4; and assessed wild-type hemagglutinin-inhibition (wt-HAI) and microneutralization (wt-MN) antibody responses (Day 0/28/56). Results Matrix-M1-adjuvanted qNIV induced 15–29% higher wt-HAI titers across 5 vaccine homologous or drifted H3N2 strains at Day 28 relative to unadjuvanted qNIV (statistically significantly superior for 5 of 6 strains tested). At Day 28, several qNIV formulations induced significantly superior wt-HAI titers vs. IIV3-HD (39–45%, 17–22%, and 44–48% greater titers for homologous A/Singapore/INFIMH-16–0019/2016—H3N2, historic-drifted A/Switzerland/9715293/2013—H3N2, and forward-drifted A/Wisconsin/19/2017—H3N2, respectively); and comparable HAI titers vs. RIV4. Wt-MN and wt-HAI data showed concordant patterns across treatment groups. Conclusion qNIV induced superior wt-HAI antibody responses vs. IIV3-HD against homologous or drifted H3N2 viruses and similar responses to RIV4. qNIV may address several critical challenges confronting current egg-derived influenza vaccines, especially in the older adult population. Disclosures All authors: No reported disclosures.

scholarly journals Effectiveness of the Cell–Derived Inactivated Quadrivalent Influenza Vaccine in Individuals at High Risk of Influenza Complications in the 2018-2019 US Influenza Season

2021 ◽  
Author(s):  
Constantina Boikos ◽  
Mahrukh Imran ◽  
Van Hung Nguyen ◽  
Thierry Ducruet ◽  
Gregg C Sylvester ◽  
...  
Keyword(s):  
High Risk ◽  
Influenza Vaccine ◽  
Influenza Season ◽  
Health Condition ◽  
Geographic Region ◽  
Vaccine Effectiveness ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Study Cohort ◽  
Medical Conditions

Abstract Background Higher rates of influenza-related morbidity and mortality occur in individuals with underlying medical conditions. To improve vaccine effectiveness, cell-based technology for influenza vaccine manufacturing has been developed. Cell–derived inactivated quadrivalent influenza vaccines (cIIV4) may improve protection in seasons where egg-propagated influenza viruses undergo mutations that affect antigenicity. This study aimed to estimate the relative vaccine effectiveness (rVE) of cIIV4 versus egg-derived inactivated quadrivalent influenza vaccines (eIIV4) in preventing influenza-related medical encounters in individuals with underlying medical conditions putting them at high risk of influenza complications during the 2018-2019 U.S. influenza season. Methods An integrated dataset, linking primary care electronic medical records with claims data, was used to conduct a retrospective cohort study among individuals aged ≥4 years, with ≥1 health condition, vaccinated with cIIV4 or eIIV4 during the 2018-2019 season. Adjusted odds ratios (ORs) were derived using a doubly robust inverse probability of treatment-weighting (IPTW) model, adjusting for age, sex, race, ethnicity, geographic region, vaccination week, and health status. rVE was estimated by (1- OR)*100 and presented with 95% confidence intervals (CI). Results The study cohort included 471,301 cIIV4 and 1,641,915 eIIV4 recipients. Compared with eIIV4, cIIV4 prevented significantly more influenza-related medical encounters among individuals with ≥1 health condition (rVE 13.4% [95% CI 11.4-15.4]); chronic pulmonary disease (18.7% [16.0-21.3]); and rheumatic disease (11.8% [3.6-19.3]). Conclusions Our findings support the use of cIIV4 in individuals ≥4 years of age at high risk of influenza complications and provide further evidence supporting improved effectiveness of cIIV4 compared to eIIV4.

scholarly journals Clinical and Economic Outcomes Associated with Cell-Based Quadrivalent Influenza Vaccine vs. Standard-Dose Egg-Based Quadrivalent Influenza Vaccines during the 2018–19 Influenza Season in the United States

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 80
Author(s):  
Girishanthy Krishnarajah ◽  
Victoria Divino ◽  
Maarten J. Postma ◽  
Stephen I. Pelton ◽  
Vamshi Ruthwik Anupindi ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Influenza Season ◽  
Standard Dose ◽  
Estimating Equation ◽  
The United States ◽  
Vaccine Effectiveness ◽  
Economic Outcomes ◽  
Influenza Vaccines ◽  
Administrative Claims ◽  
Respiratory Event

Non-egg-based influenza vaccines eliminate the potential for egg-adapted mutations and potentially increase vaccine effectiveness. This retrospective study compared hospitalizations/emergency room (ER) visits and all-cause annualized healthcare costs among subjects aged 4–64 years who received cell-based quadrivalent (QIVc) or standard-dose egg-based quadrivalent (QIVe-SD) influenza vaccine during the 2018–19 influenza season. Administrative claims data (IQVIA PharMetrics® Plus, IQVIA, USA) were utilized to evaluate clinical and economic outcomes. Adjusted relative vaccine effectiveness (rVE) of QIVc vs. QIVe-SD among overall cohort, as well as for three subgroups (age 4–17 years, age 18–64 years, and high-risk) was evaluated using inverse probability of treatment weighting (IPTW) and Poisson regression models. Generalized estimating equation models among the propensity score matched sample were used to estimate annualized all-cause costs. A total of 669,030 recipients of QIVc and 3,062,797 of QIVe-SD were identified after IPTW adjustments. Among the overall cohort, QIVc had higher adjusted rVEs against hospitalizations/ER visits related to influenza, all-cause hospitalizations, and hospitalizations/ER visits associated with any respiratory event compared to QIVe-SD. The adjusted annualized all-cause total costs were higher for QIVe-SD compared to QIVc ((+$461); p < 0.05).

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 Understanding Immunity in Children Vaccinated With Live Attenuated Influenza Vaccine

2019 ◽  
Vol 9 (Supplement_1) ◽  
pp. S10-S14 ◽  
Author(s):  
Ian Shannon ◽  
Chantelle L White ◽  
Jennifer L Nayak
Keyword(s):  
Influenza Vaccine ◽  
Natural Infection ◽  
The United States ◽  
Influenza Vaccines ◽  
Upper Respiratory Tract ◽  
Immune Protection ◽  
Live Attenuated Influenza Vaccine ◽  
Current State ◽  
Upper Respiratory ◽  
Attenuated Viruses

Abstract Live attenuated influenza vaccine (LAIV), or FluMist, was approved for use in the United States in 2003. This vaccine, administered intranasally, offers the advantage of stimulating immunity at the site of infection in the upper respiratory tract and, by mimicking natural infection, has the potential to elicit a multifaceted immune response. However, the development of immunity following LAIV administration requires viral replication, causing vaccine effectiveness to be impacted by both the replicative fitness of the attenuated viruses being administered and the degree of the host’s preexisting immunity. In this review, we discuss the current state of knowledge regarding the mechanisms of protection elicited by LAIV in children, contrast this with immune protection that develops upon vaccination with inactivated influenza vaccines, and briefly discuss both the potential advantages as well as challenges offered by this vaccination platform.

scholarly journals Prediction of influenza vaccine effectiveness for the influenza season 2017/18 in the US

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2067 ◽  
Author(s):  
Slobodan Paessler ◽  
Veljko Veljkovic
Keyword(s):  
Influenza Vaccine ◽  
Seasonal Influenza ◽  
Influenza Season ◽  
Vaccine Effectiveness ◽  
Influenza Viruses ◽  
Antigenic Drift ◽  
Correct Prediction ◽  
Seasonal Influenza Vaccine ◽  
The Us ◽  
Key Factor

Vaccination against seasonal influenza viruses is the most effective way to prevent infection. A key factor in the effectiveness of the seasonal influenza vaccine is its immunological compatibility with the circulating viruses during the season. The high evolutionary rate, antigenic shift and antigenic drift of influenza viruses, represents the main obstacle for correct prediction of the vaccine effectiveness for an upcoming flu season. Conventional structural and phylogenetic approaches for assessment of vaccine effectiveness have had a limited success in prediction of vaccine efficacy in the past. Recently, a novel bioinformatics approach for assessment of effectiveness of seasonal influenza vaccine was proposed. Here, this approach was used for prediction of the vaccine effectiveness for the influenza season 2017/18 in US.

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