Vaccine effectiveness of live attenuated and trivalent inactivated influenza vaccination in 2010/11 to 2015/16: the SIVE II record linkage study
Authors: Simpson Colin R , Lone Nazir I , Kavanagh Kim , Englishby Tanya , Robertson Chris , McMenamin Jim , Wissman Beatrix von , Vasileiou Eleftheria , Butler Christopher C , Ritchie Lewis D , Gunson Rory , Schwarze Jürgen , Sheikh Aziz 
Published: December 2020

Background
There is good evidence of vaccine effectiveness in healthy individuals but less robust evidence for vaccine effectiveness in the populations targeted for influenza vaccination. The live attenuated influenza vaccine (LAIV) has recently been recommended for children in the UK. The trivalent influenza vaccine (TIV) is recommended for all people aged ≥ 65 years and for those aged < 65 years who are at an increased risk of complications from influenza infection (e.g. people with asthma).

Objective
To examine the vaccine effectiveness of LAIV and TIV.

Design
Cohort study and test-negative designs to estimate vaccine effectiveness. A self-case series study to ascertain adverse events associated with vaccination.

Setting
A national linkage of patient-level general practice (GP) data from 230 Scottish GPs to the Scottish Immunisation & Recall Service, Health Protection Scotland virology database, admissions to Scottish hospitals and the Scottish death register.

Participants
A total of 1,250,000 people.

Interventions
LAIV for 2- to 11-year-olds and TIV for older people (aged ≥ 65 years) and those aged < 65 years who are at risk of diseases, from 2010/11 to 2015/16.

Main outcome measures
The main outcome measures include vaccine effectiveness against laboratory-confirmed influenza using real-time reverse-transcription polymerase chain reaction (RT-PCR), influenza-related morbidity and mortality, and adverse events associated with vaccination.

Results
Two-fifths (40%) of preschool-aged children and three-fifths (60%) of primary school-aged children registered in study practices were vaccinated. Uptake varied among groups [e.g. most affluent vs. most deprived in 2- to 4-year-olds, odds ratio 1.76, 95% confidence interval (CI) 1.70 to 1.82]. LAIV-adjusted vaccine effectiveness among children (aged 2–11 years) for preventing RT-PCR laboratory-confirmed influenza was 21% (95% CI –19% to 47%) in 2014/15 and 58% (95% CI 39% to 71%) in 2015/16. No significant adverse events were associated with LAIV. Among at-risk 18- to 64-year-olds, significant trivalent influenza vaccine effectiveness was found for four of the six seasons, with the highest vaccine effectiveness in 2010/11 (53%, 95% CI 21% to 72%). The seasons with non-significant vaccine effectiveness had low levels of circulating influenza virus (2011/12, 5%; 2013/14, 9%). Among those people aged ≥ 65 years, TIV effectiveness was positive in all six seasons, but in only one of the six seasons (2013/14) was significance achieved (57%, 95% CI 20% to 76%).

Conclusions
The study found that LAIV was safe and effective in decreasing RT-PCR-confirmed influenza in children. TIV was safe and significantly effective in most seasons for 18- to 64-year-olds, with positive vaccine effectiveness in most seasons for those people aged ≥ 65 years (although this was significant in only one season).

Future work
The UK Joint Committee on Vaccination and Immunisation has recommended the use of adjuvanted injectable vaccine for those people aged ≥ 65 years from season 2018/19 onwards. A future study will be required to evaluate this vaccine.

Trial registration
Current Controlled Trials ISRCTN88072400.

Funding
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 67. See the NIHR Journals Library website for further project information.