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.

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 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 Influenza vaccine effectiveness against hospitalization in the United States, 2019-2020

2020 ◽  
Author(s):  
Mark W Tenforde ◽  
H Keipp Talbot ◽  
Christopher H Trabue ◽  
Manjusha Gaglani ◽  
Tresa M McNeal ◽  
...  
Keyword(s):  
United States ◽  
Influenza Vaccine ◽  
Influenza Vaccination ◽  
Respiratory Illness ◽  
The United States ◽  
Vaccine Effectiveness ◽  
Influenza Viruses ◽  
Current Season ◽  
Hospital Resources ◽  
Negative Controls

Abstract Background Influenza causes significant morbidity and mortality and stresses hospital resources during periods of increased circulation. We evaluated the effectiveness of the 2019-2020 influenza vaccine against influenza-associated hospitalizations in the United States. Methods We included adults hospitalized with acute respiratory illness at 14 hospitals and tested for influenza viruses by reserve transcription polymerase chain reaction. Vaccine effectiveness (VE) was estimated by comparing the odds of current-season influenza vaccination in test-positive influenza cases versus test-negative controls, adjusting for confounders. VE was stratified by age and major circulating influenza types along with A(H1N1)pdm09 genetic subgroups. Results 3116 participants were included, including 18% (553) influenza-positive cases. Median age was 63 years. Sixty-seven percent (2079) received vaccination. Overall adjusted VE against influenza viruses was 41% (95% confidence interval [CI]: 27-52). VE against A(H1N1)pdm09 viruses was 40% (95% CI: 24-53) and 33% against B viruses (95% CI: 0-56). Of the two major A(H1N1)pdm09 subgroups (representing 90% of sequenced H1N1 viruses), VE against one group (5A+187A,189E) was 59% (95% CI: 34-75) whereas no significant VE was observed against the other group (5A+156K) [-1%, 95% CI: -61-37]. Conclusions In a primarily older population, influenza vaccination was associated with a 41% reduction in risk of hospitalized influenza illness.

scholarly journals Influenza Vaccine Effectiveness in the United States During the 2016–2017 Season

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S451-S452
Author(s):  
Brendan Flannery ◽  
Jessie Chung ◽  
Arnold S Monto ◽  
Emily T Martin ◽  
Edward Belongia ◽  
...  
Keyword(s):  
United States ◽  
Influenza Vaccine ◽  
The United States ◽  
Vaccine Effectiveness

scholarly journals Influenza vaccine effectiveness among patients with high-risk medical conditions in the United States, 2012–2016

Vaccine ◽  
2018 ◽  
Vol 36 (52) ◽  
pp. 8047-8053 ◽  
Author(s):  
Mei Shang ◽  
Jessie R. Chung ◽  
Michael L. Jackson ◽  
Lisa A. Jackson ◽  
Arnold S. Monto ◽  
...  
Keyword(s):  
United States ◽  
High Risk ◽  
Influenza Vaccine ◽  
The United States ◽  
Vaccine Effectiveness ◽  
Medical Conditions

scholarly journals 150. Relative Effectiveness of High-Dose and Standard-Dose Influenza Vaccine Against Influenza-Related Hospitalization Among Older Adults—United States, 2015–2017

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S10-S10
Author(s):  
Joshua Doyle ◽  
Lauren Beacham ◽  
Elif Alyanak ◽  
Manjusha Gaglani ◽  
Emily T Martin ◽  
...  
Keyword(s):  
United States ◽  
Older Adults ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Standard Dose ◽  
Relative Effectiveness ◽  
The United States ◽  
Vaccine Effectiveness ◽  
High Dose ◽  
Research Grant

Abstract Background Seasonal influenza causes substantial morbidity and mortality, and older adults are disproportionately affected. Newer vaccines have been developed for use in people 65 years and older, including a trivalent inactivated vaccine with a 4-fold higher dose of antigen (IIV-HD). In recent years, the use of IIV-HD has increased sufficiently to evaluate its effectiveness compared with standard-dose inactivated influenza vaccines (IIV-SD). Methods Hospitalized patients with acute respiratory illness were enrolled in an observational vaccine effectiveness study at 8 hospitals in 4 states participating in the United States Hospitalized Adult Influenza Vaccine Effectiveness Network during the 2015–2016 and 2016–2017 influenza seasons. Predominant influenza A virus subtypes were H1N1 and H3N2, respectively, during these seasons. All enrolled patients were tested for influenza virus with polymerase chain reaction. Receipt and type of influenza vaccine was determined from electronic records and chart review. Odds of laboratory-confirmed influenza were compared among vaccinated and unvaccinated patients. Relative odds of laboratory-confirmed influenza were determined for patients who received IIV-HD or IIV-SD, and adjusted for potential confounding variables via logistic regression. Results Among 1,744 enrolled patients aged ≥ 65 years, 1,105 (63%) were vaccinated; among those vaccinated, 621 (56%) received IIV-HD and 484 (44%) received IIV-SD. Overall, 315 (18%) tested positive for influenza, including 97 (6%) who received IIV-HD, 86 (5%) who received IIV-SD, and 132 (8%) who were unvaccinated. Controlling for age, race, sex, enrollment site, date of illness, index of comorbidity, and influenza season, the adjusted odds of influenza among patients vaccinated with IIV-HD vs. IIV-SD were 0.72 (P = 0.06, 95% CI: 0.52 to 1.01). Conclusion Comparison of high-dose vs. standard-dose vaccine effectiveness during 2 recent influenza seasons (1 H1N1 and 1 H3N2-predominant) suggested relative benefit (nonsignificant) of high-dose influenza vaccine in protecting against influenza-associated hospitalization among persons aged 65 years and older; additional years of data are needed to confirm this finding. Disclosures H. K. Talbot, sanofi pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none.

scholarly journals Influenza Vaccine Effectiveness in the United States During the 2016–2017 Season

2018 ◽  
Vol 68 (11) ◽  
pp. 1798-1806 ◽  
Author(s):  
Brendan Flannery ◽  
Jessie R Chung ◽  
Arnold S Monto ◽  
Emily T Martin ◽  
Edward A Belongia ◽  
...  
Keyword(s):  
United States ◽  
Influenza Vaccine ◽  
The United States ◽  
Vaccine Effectiveness

Cost-effectiveness of live attenuated influenza vaccine versus inactivated influenza vaccine among children aged 24–59 months in the United States

Vaccine ◽  
2008 ◽  
Vol 26 (23) ◽  
pp. 2841-2848 ◽  
Author(s):  
Bryan R. Luce ◽  
Kristin L. Nichol ◽  
Robert B. Belshe ◽  
Kevin D. Frick ◽  
Su Xia Li ◽  
...  
Keyword(s):  
United States ◽  
Cost Effectiveness ◽  
Influenza Vaccine ◽  
The United States ◽  
Live Attenuated Influenza Vaccine

scholarly journals Influenza Vaccine Effectiveness in the United States during the 2015–2016 Season

2017 ◽  
Vol 377 (6) ◽  
pp. 534-543 ◽  
Author(s):  
Michael L. Jackson ◽  
Jessie R. Chung ◽  
Lisa A. Jackson ◽  
C. Hallie Phillips ◽  
Joyce Benoit ◽  
...  
Keyword(s):  
United States ◽  
Influenza Vaccine ◽  
The United States ◽  
Vaccine Effectiveness

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.

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