scholarly journals Successes and Failures of the Live-attenuated Influenza Vaccine: Can We Do Better?

2019 ◽  
Vol 70 (6) ◽  
pp. 1029-1037 ◽  
Author(s):  
Laura Matrajt ◽  
M Elizabeth Halloran ◽  
Rustom Antia
Keyword(s):  
Influenza Vaccine ◽  
Mathematical Models ◽  
Vaccine Strain ◽  
Influenza Season ◽  
Mechanistic Explanation ◽  
Vaccine Effectiveness ◽  
Challenge Strain ◽  
Influenza Strain ◽  
Live Attenuated Influenza Vaccine ◽  
The World

Abstract Background The effectiveness of the live-attenuated influenza vaccine (LAIV) can vary widely, ranging from 0% to 50%. The reasons for these discrepancies remain largely unclear. Methods We use mathematical models to explore how the efficacy of LAIV is affected by the degree of mismatch with the currently circulating influenza strain and interference with pre-existing immunity. The models incorporate 3 key antigenic distances: the distances between the vaccine strain, pre-existing immunity, and the challenge strain. Results Our models show that an LAIV that is matched with the currently circulating strain is likely to have only modest efficacy. Our results suggest that the efficacy of the vaccine would be increased (optimized) if, rather than being matched to the circulating strain, it is antigenically slightly further from pre-existing immunity than the circulating strain. The models also suggest 2 regimes in which LAIV that is matched to circulating strains may be protective: in children before they have built immunity to circulating strains and in response to novel strains (such as antigenic shifts) which are at substantial antigenic distance from previously circulating strains. We provide an explanation for the variation in vaccine effectiveness between studies and countries of vaccine effectiveness observed during the 2014–2015 influenza season. Conclusions LAIV is offered to children across the world; however, its effectiveness significantly varies between studies. Here, we propose a mechanistic explanation to understand these differences. We further propose a way to select the LAIV strain that would have a higher chance of being protective.

scholarly journals Successes and failures of the live-attenuated influenza vaccine, can we do better?

2018 ◽  
Author(s):  
Laura Matrajt ◽  
M. Elizabeth Halloran ◽  
Rustom Antia
Keyword(s):  
United States ◽  
Influenza Vaccine ◽  
Mathematical Models ◽  
Viral Infections ◽  
Influenza Season ◽  
The United States ◽  
Vaccine Effectiveness ◽  
Effective Protection ◽  
Live Attenuated Vaccines ◽  
Live Attenuated Influenza Vaccine

Live-attenuated vaccines are usually highly effective against many acute viral infections. However, the effective- ness of the live attenuated influenza vaccine (LAIV) can vary widely, ranging from 0% effectiveness in some studies done in the United States to 50% in studies done in Europe. The reasons for these discrepancies remain largely unclear. In this paper we use mathematical models to explore how the efficacy of LAIV is affected by the degree of mismatch with the currently circulating influenza strain and interference with pre-existing immunity. The model incorporates two key antigenic distances - the distance between pre-existing immunity and the currently circulating strain as well as the LAIV strain. Our models show that a LAIV that is matched with the currently circulating strain is likely to have only modest efficacy. Our results suggest that the efficacy of the vaccine would be increased (optimized) if, rather than being matched to the circulating strain, it is antigenically slightly further from pre-existing immunity compared with the circulating strain. The models also suggest two regimes in which LAIV that is matched to circulating strains may provide effective protection. The first is in children before they have built immunity from circulating strains. The second is in response to novel strains (such as antigenic shifts) which are at substantial antigenic distance from previously circulating strains. Our models provide an explanation for the variation in vaccine effectiveness, both between children and adults as well as between studies of vaccine effectiveness observed during the 2014-15 influenza season in different countries.

Intraseason decline in influenza vaccine effectiveness during the 2016 southern hemisphere influenza season: A test-negative design study and phylogenetic assessment

Vaccine ◽  
2019 ◽  
Vol 37 (19) ◽  
pp. 2634-2641 ◽  
Author(s):  
Annette K. Regan ◽  
James E. Fielding ◽  
Monique B. Chilver ◽  
Kylie S. Carville ◽  
Cara A. Minney-Smith ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Southern Hemisphere ◽  
Influenza Season ◽  
Vaccine Effectiveness ◽  
Design Study

Influenza Vaccine Effectiveness Among Children for the 2017–2018 Season

2019 ◽  
Vol 9 (4) ◽  
pp. 468-473 ◽  
Author(s):  
Lauren N Powell ◽  
Rodolfo E Bégué
Keyword(s):  
Influenza Vaccine ◽  
Influenza A ◽  
Influenza Season ◽  
Vaccine Effectiveness ◽  
Influenza B ◽  
Immunization Registry ◽  
Previous Season ◽  
Waning Immunity ◽  
Small Benefit ◽  
Susceptible Populations

Abstract Background The 2017–2018 influenza season was of high severity. Circulating influenza strains change periodically, making it important to determine vaccine effectiveness on an annual basis, especially for susceptible populations. The primary aim of our study was to estimate the effectiveness of the influenza vaccine among children. Secondary aims were to assess the effect of previous season vaccination and intraseasonal waning of immunity. Methods Children 6 months to 17 years of age tested for influenza during the 2017–2018 season were included. Clinical charts were reviewed, and immunization status was confirmed via the Louisiana Immunization Registry. Influenza vaccine effectiveness (IVE) was estimated in a test-negative design by comparing vaccination status of influenza-positive vs influenza-negative cases. Results A total of 3595 children were included, 26% of whom tested positive for influenza, mostly type A (79%); 15% had received an influenza vaccine prior to illness: 8% among the influenza-positive and 17% among influenza-negative cases (P <.0001). IVE for the 2017–2018 influenza season was 52% overall (95% confidence interval, 38%–62%), 49% for influenza A, and 60% for influenza B. While receiving current year (2017–2018) vaccine had the most effect, receiving the previous year (2016–2017) vaccine had a small benefit and no interference. We found no evidence of waning immunity of the vaccine for the 2017–2018 season. Conclusions IVE was moderate for children. Previous year vaccination had a small but significant benefit and there was no evidence of waning immunity in our cohort. Ongoing national and local surveillance is important to understand the benefit of influenza vaccination.

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 1341. Relative Vaccine Effectiveness Against Influenza-related Hospitalizations and Respiratory Events During the 2019/20 Influenza seAson in U.S. Children and Adults. A Real-World Evidence Comparison Between Quadrivalent Cell-based and Egg-based Influenza Vaccines

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S758-S758
Author(s):  
Stephen I Pelton ◽  
Maarten Postma ◽  
Victoria Divino ◽  
Joaquin F Mould-Quevedo ◽  
Ruthwik Anupindi ◽  
...  
Keyword(s):  
High Risk ◽  
Influenza Vaccine ◽  
Influenza Season ◽  
Standard Dose ◽  
The United States ◽  
Negative Control ◽  
Vaccine Effectiveness ◽  
Administrative Claims ◽  
Real World Evidence ◽  
Quadrivalent Influenza Vaccine

Abstract Background Non-egg-based influenza vaccine manufacturing reduces egg adaptation and therefore has the potential to increase vaccine effectiveness. This study evaluated whether the cell-based quadrivalent influenza vaccine (QIVc) improved relative vaccine effectiveness (rVE) compared to standard-dose egg-based quadrivalent influenza vaccine (QIVe-SD) in the reduction of influenza-related and respiratory-related hospitalizations/emergency room (ER) visits among subjects 4-64 years old during the 2019/20 influenza season. Methods A retrospective analysis was conducted among subjects 4-64 years old vaccinated with QIVc or QIVe-SD using administrative claims data in the United States of America (U.S.) (IQVIA PharMetrics® Plus). Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounders. Post-IPTW, the number of events and rates (per 1,000 vaccinated subject-seasons) of influenza-related hospitalizations/ER visits, respiratory-related hospitalizations/ER visits and all-cause hospitalizations were assessed. Poisson regression was used to estimate adjusted rVE. To avoid any influenza outcome misclassification with COVID-19 infection, the study period ended March 7,2020. A sub-analysis for a high-risk subgroup was conducted. Urinary tract infection (UTI) hospitalization was assessed as a negative control endpoint. Results During the 2019/20 influenza season, 1,150,134 QIVc and 3,924,819 QIVe-SD recipients were identified post-IPTW. Overall adjusted analyses (4-64 years old) found that QIVc was associated with a significantly higher rVE compared to QIVe-SD against influenza-related hospitalizations/ER visits (5.3% [95% CI: 0.5%-9.9%]), all-cause hospitalizations (14.5% [95% CI: 13.1%-15.8%]) and any respiratory-related hospitalization/ER visit (8.2% [95% CI: 6.5%-9.8%]). A similar trend was seen for the high-risk subgroup; for instance, rVE for QIVc compared to QIVe-SD against influenza-related hospitalizations/ER visits was 10.5% [95% CI: 2.9%-17.4%]. No effect was identified for the negative control outcome. Conclusion QIVc was significantly more effective in preventing influenza-related and respiratory-related hospitalizations/ER visits, as well as all-cause hospitalizations, compared to QIVe-SD. Disclosures Stephen I. Pelton, MD, Seqirus (Consultant) Maarten Postma, Dr., Seqirus (Consultant) Victoria Divino, PhD, Seqirus (Consultant) Joaquin F. Mould-Quevedo, PhD, Seqirus (Employee) Ruthwik Anupindi, PhD, Seqirus (Consultant) Mitchell DeKoven, PhD, Seqirus (Consultant) myron J. levin, MD, GSK group of companies (Employee, Research Grant or Support)

scholarly journals Late season interim estimates of influenza vaccine effectiveness reliably predict end of season estimates in Victoria, Australia, 2007 to 2012

2013 ◽  
Vol 18 (41) ◽  
Author(s):  
S G Sullivan ◽  
H Kelly
Keyword(s):  
Influenza Vaccine ◽  
World Health Organization ◽  
Influenza A ◽  
Vaccine Effectiveness ◽  
Strain Selection ◽  
World Health ◽  
Percentage Points ◽  
The World ◽  
Influenza Activity ◽  
Health Organization

Twice each year the World Health Organization makes a recommendation for the composition of the influenza vaccine, based on circulating strains of influenza A(H3N2), A(H1N1) and B. Strain selection has always been based on immunogenicity studies with limited human data. Immunogenicity can be considered as a proxy for vaccine effectiveness (VE). However, only interim VE estimates for the target hemisphere can be considered in time for the strain selection meeting. Using surveillance data from Victoria, Australia, we retrospectively estimated and compared interim and final VE estimates for 2007 to 2012. In general, interim estimates were within five percentage points of final estimates. However, estimates made too early or in years of low influenza activity may be unreliable.

scholarly journals Effects of Influenza Vaccination in the United States During the 2018–2019 Influenza Season

2020 ◽  
Vol 71 (8) ◽  
pp. e368-e376 ◽  
Author(s):  
Jessie R Chung ◽  
Melissa A Rolfes ◽  
Brendan Flannery ◽  
Pragati Prasad ◽  
Alissa O’Halloran ◽  
...  
Keyword(s):  
United States ◽  
Influenza Vaccine ◽  
Influenza Vaccination ◽  
Influenza Season ◽  
The United States ◽  
Vaccine Effectiveness ◽  
Influenza Viruses ◽  
Monte Carlo Algorithm ◽  
Medical Visits ◽  
The Us

Abstract Background Multivalent influenza vaccine products provide protection against influenza A(H1N1)pdm09, A(H3N2), and B lineage viruses. The 2018–2019 influenza season in the United States included prolonged circulation of A(H1N1)pdm09 viruses well-matched to the vaccine strain and A(H3N2) viruses, the majority of which were mismatched to the vaccine. We estimated the number of vaccine-prevented influenza-associated illnesses, medical visits, hospitalizations, and deaths for the season. Methods We used a mathematical model and Monte Carlo algorithm to estimate numbers and 95% uncertainty intervals (UIs) of influenza-associated outcomes prevented by vaccination in the United States. The model incorporated age-specific estimates of national 2018–2019 influenza vaccine coverage, influenza virus–specific vaccine effectiveness from the US Influenza Vaccine Effectiveness Network, and disease burden estimated from population-based rates of influenza-associated hospitalizations through the Influenza Hospitalization Surveillance Network. Results Influenza vaccination prevented an estimated 4.4 million (95%UI, 3.4 million–7.1 million) illnesses, 2.3 million (95%UI, 1.8 million–3.8 million) medical visits, 58 000 (95%UI, 30 000–156 000) hospitalizations, and 3500 (95%UI, 1000–13 000) deaths due to influenza viruses during the US 2018–2019 influenza season. Vaccination prevented 14% of projected hospitalizations associated with A(H1N1)pdm09 overall and 43% among children aged 6 months–4 years. Conclusions Influenza vaccination averted substantial influenza-associated disease including hospitalizations and deaths in the United States, primarily due to effectiveness against A(H1N1)pdm09. Our findings underscore the value of influenza vaccination, highlighting that vaccines measurably decrease illness and associated healthcare utilization even in a season in which a vaccine component does not match to a circulating virus.

scholarly journals Poor Immunogenicity, Not Vaccine Strain Egg Adaptation, May Explain the Low H3N2 Influenza Vaccine Effectiveness in 2012–2013

2018 ◽  
Vol 67 (3) ◽  
pp. 327-333 ◽  
Author(s):  
Sarah Cobey ◽  
Sigrid Gouma ◽  
Kaela Parkhouse ◽  
Benjamin S Chambers ◽  
Hildegund C Ertl ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Vaccine Strain ◽  
Vaccine Effectiveness ◽  
H3n2 Influenza
Sign in / Sign up

Export Citation Format

Share Document