scholarly journals Presence of defective viral genes in H1N1 live attenuated influenza vaccine strains is not associated with reduced human cell fitness or vaccine effectiveness

Vaccine ◽  
2021 ◽  
Author(s):  
Sameer Ayaz ◽  
Oliver Dibben ◽  
David Chapman
Keyword(s):  
Influenza Vaccine ◽  
Human Cell ◽  
Vaccine Effectiveness ◽  
Live Attenuated Influenza Vaccine ◽  
Viral Genes

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.

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.

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 Multicenter Study of Live-Attenuated Influenza Vaccine Effectiveness in Children, 2014–15

2015 ◽  
Vol 2 (suppl_1) ◽  
Author(s):  
Herve Caspard ◽  
Manjusha Gaglani ◽  
Lydia Clipper ◽  
Edward A. Belongia ◽  
Huong Q. Mclean ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Multicenter Study ◽  
Vaccine Effectiveness ◽  
Live Attenuated Influenza Vaccine

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.

Live attenuated influenza vaccine (LAIV): recent effectiveness results from the USA and implications for LAIV programmes elsewhere

2017 ◽  
Vol 103 (1) ◽  
pp. 101-105 ◽  
Author(s):  
Richard Pebody ◽  
Jim McMenamin ◽  
Hanna Nohynek
Keyword(s):  
Influenza Vaccine ◽  
Influenza Vaccination ◽  
Vaccination Programme ◽  
Vaccine Effectiveness ◽  
Monitoring Programme ◽  
End Points ◽  
Apparent Lack ◽  
Live Attenuated Influenza Vaccine ◽  
The Usa ◽  
The Uk

The USA has a long-standing paediatric influenza vaccination programme, including use of live attenuated influenza vaccine (LAIV). Following US evidence of apparent lack of vaccine effectiveness (VE) of LAIV in 2015/2016, particularly against A(H1N1)pdm09, the USA suspended the use of LAIV in the 2016/2017 season. The UK introduced LAIV for children in 2013/2014 and Finland in 2015/2016. Both countries have since been closely monitoring programme performance. In 2015/2016, the UK and Finland, unlike the USA, found evidence of significant VE of LAIV against laboratory-confirmed influenza. Several studies, however, reported relatively lower VE of LAIV against A(H1N1)pdm09 infection compared with inactivated influenza vaccine, although not for A(H3N2) or B. The reasons for these apparent differences remain under investigation. Both the UK and Finland continue to recommend the use of LAIV in children for the 2017/2018 season and are intensifying further monitoring of their childhood programmes against a range of end-points.

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