scholarly journals The Consequences of Egg Adaptation in the H3N2 Component to the Immunogenicity of Live Attenuated Influenza Vaccine

2019 ◽  
Author(s):  
Daniel H. Goldhill ◽  
Benjamin Lindsey ◽  
Ruthiran Kugathasan ◽  
Zandra Felix Garza ◽  
Ya Jankey Jagne ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Vaccine Effectiveness ◽  
Sequence Diversity ◽  
Antibody Responses ◽  
Wildtype Strain ◽  
Adaptive Mutations ◽  
Live Attenuated Influenza Vaccine ◽  
Mucosal Antibody

AbstractAdaptation in egg-passaged vaccine strains may cause reduced vaccine effectiveness due to altered antigenicity of the influenza haemagglutinin. We tested whether egg adaptation modified serum and mucosal antibody responses to the A(H3N2) component in the Live Attenuated Influenza Vaccine (LAIV). Twice as many children seroconverted to an egg-adapted H3N2 than the equivalent wildtype strain. Seroconversion to the wildtype strain was greater in children seronegative pre-LAIV, whereas higher mucosal IgA responses to wildtype antigen were observed if seropositive prior to vaccination. Sequencing of virus from nasopharyngeal swabs from 7 days post-LAIV showed low sequence diversity and no reversion of egg-adaptive mutations.

scholarly journals High-Affinity H7 Head and Stalk Domain–Specific Antibody Responses to an Inactivated Influenza H7N7 Vaccine After Priming With Live Attenuated Influenza Vaccine

2015 ◽  
Vol 212 (8) ◽  
pp. 1270-1278 ◽  
Author(s):  
Jessica L. Halliley ◽  
Surender Khurana ◽  
Florian Krammer ◽  
Theresa Fitzgerald ◽  
Elizabeth M. Coyle ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Specific Antibody ◽  
Antibody Responses ◽  
Domain Specific ◽  
High Affinity ◽  
Live Attenuated Influenza Vaccine ◽  
Stalk Domain

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 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 2 Influenza Vaccines in Nationwide Cohorts of Finnish 2-Year-Old Children in the Seasons 2015–2016 Through 2017–2018

2020 ◽  
Vol 71 (8) ◽  
pp. e255-e261
Author(s):  
Ulrike Baum ◽  
Sangita Kulathinal ◽  
Kari Auranen ◽  
Hanna Nohynek
Keyword(s):  
Influenza Vaccine ◽  
Virus Type ◽  
Real Life ◽  
Vaccine Effectiveness ◽  
Influenza Vaccines ◽  
Type B ◽  
Live Attenuated Influenza Vaccine ◽  
Vaccine Type ◽  
Decision Making Processes ◽  
Study Population

Abstract Background From 2015–2016 through 2017–2018, injectable, trivalent inactivated influenza vaccines (IIV3) and a nasal spray, tetravalent live-attenuated influenza vaccine (LAIV4) were used in parallel in Finland. To understand how well vaccination with each vaccine type protected children against influenza under real-life conditions, vaccine effectiveness in 2-year-olds was estimated for all 3 seasons. Methods Each season, a nationwide register-based cohort study was conducted. The study population comprised 60 088, 60 860, and 60 345 children in 2015–2016, 2016–2017, and 2017–2018, respectively. Laboratory-confirmed influenza was the study outcome. Seasonal influenza vaccination with either LAIV4 or IIV3 was the time-dependent exposure of interest. Vaccine effectiveness was defined as 1 minus the hazard ratio comparing vaccinated with unvaccinated children. Results From 2015–2016 through 2017–2018, the effectiveness of LAIV4 against influenza of any virus type was estimated at 54.2% (95% confidence interval, 32.2–69.0%), 20.3% (−12.7%, 43.6%), and 30.5% (10.9–45.9%); the corresponding effectiveness of IIV3 was 77.2% (48.9–89.8%), 24.5% (−29.8%, 56.1%), and −20.1% (−61.5%, 10.7%). Neither influenza vaccine clearly excelled in protecting children. The LAIV4 effectiveness against type B was greater than against type A and greater than the IIV3 effectiveness against type B. Conclusions To understand how influenza vaccines could be improved, vaccine effectiveness must be analyzed by vaccine and virus type. Effectiveness estimates also expressing overall protection levels are needed to guide individual and programmatic decision-making processes. Supported by this analysis, the vaccination program in Finland now recommends LAIV4 and injectable, tetravalent inactivated influenza vaccines replacing IIV3.

Measuring Antibody Responses to a Live Attenuated Influenza Vaccine in Children

2004 ◽  
Vol 23 (9) ◽  
pp. 852-856 ◽  
Author(s):  
Min-Shi Lee ◽  
Kutubuddin Mahmood ◽  
Lopa Adhikary ◽  
Marilyn J. August ◽  
Julie Cordova ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Antibody Responses ◽  
Live Attenuated Influenza Vaccine

scholarly journals Differences in Antibody Responses Between Trivalent Inactivated Influenza Vaccine and Live Attenuated Influenza Vaccine Correlate With the Kinetics and Magnitude of Interferon Signaling in Children

2014 ◽  
Vol 210 (2) ◽  
pp. 224-233 ◽  
Author(s):  
Raquel G. Cao ◽  
Nicolas M. Suarez ◽  
Gerlinde Obermoser ◽  
Santiago M. C. Lopez ◽  
Emilio Flano ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Antibody Responses ◽  
Interferon Signaling ◽  
Live Attenuated Influenza Vaccine

scholarly journals Defining the root cause of reduced H1N1 live attenuated influenza vaccine effectiveness: low viral fitness leads to inter-strain competition

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Oliver Dibben ◽  
Jonathan Crowe ◽  
Shaun Cooper ◽  
Laura Hill ◽  
Katarzyna E. Schewe ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
New Caledonia ◽  
Vaccine Effectiveness ◽  
Viral Fitness ◽  
Wild Type Virus ◽  
Significant Protection ◽  
Wild Type ◽  
Virus Shedding ◽  
Live Attenuated Influenza Vaccine ◽  
Strain Competition

AbstractIn the 2013–14 and 2015–16 influenza seasons, reduced vaccine effectiveness (VE) was observed for the H1N1 component of the FluMist quadrivalent live attenuated influenza vaccine (QLAIV) in the USA, leading to loss of Advisory Committee on Immunization Practices recommendation. Here we demonstrate in ferrets that 2015–16A/H1N1pdm09 vaccine strain A/Bolivia/559/2013 (A/BOL13) is outcompeted in trivalent (TLAIV) and QLAIV formulations, leading to reduced protection from wild-type challenge. While monovalent (MLAIV) A/BOL13 provided significant protection from wild-type virus shedding and fever at doses as low as 3.0 log10 fluorescent focus units (FFU), it failed to provide a similar level of protection in TLAIV or QLAIV formulation, even at a 6.0 log10 FFU dose. Conversely, clinically effective H1N1 strain A/New Caledonia/20/1999 provided significant protection in MLAIV, TLAIV, and QLAIV formulations. In conclusion, reduced A/BOL13 replicative fitness rendered it susceptible to inter-strain competition in QLAIV, contributing to its reduced VE in the 2015–16 season.

scholarly journals Live attenuated influenza vaccine effectiveness against hospitalisation due to laboratory-confirmed influenza in children two to six years of age in England in the 2015/16 season

2017 ◽  
Vol 22 (4) ◽  
Author(s):  
Richard Pebody ◽  
Bersabeh Sile ◽  
Fiona Warburton ◽  
Mary Sinnathamby ◽  
Camille Tsang ◽  
...  
Keyword(s):  
United Kingdom ◽  
Confidence Interval ◽  
Influenza Vaccine ◽  
Influenza Vaccination ◽  
Vaccination Programme ◽  
Screening Method ◽  
Vaccine Effectiveness ◽  
Live Attenuated Influenza Vaccine ◽  
The United Kingdom ◽  
Roll Out

The United Kingdom is introducing a universal annual influenza vaccination programme for children. Live attenuated influenza vaccine (LAIV) effectiveness (VE) against laboratory-confirmed influenza hospitalisation in 2 to 6 year-olds in England was measured in 2015/16 using the screening method. VE adjusted for age, geography and month was 54.5% (95% confidence interval (CI): 31.5% to 68.4%) for all influenza types combined; 48.3% (95% CI: 16.9% to 67.8%) for A(H1N1)pdm09 and 70.6% (95% CI: 33.2% to 87.1%) for B. The findings support on-going programme roll-out.

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.

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