The Lancet Infectious Diseases
Jun 2013   Volume 13  Number 6  p465 – 558
http://www.thelancet.com/journals/laninf/issue/current

Comment
AS03-adjuvanted influenza vaccine in elderly people
Julie E Ledgerwood

Preview
The best available method for prevention of influenza is vaccination. However, the effectiveness of inactivated trivalent influenza vaccine (TIV) is variable, generally reaching 60% in the overall population when vaccine strains and outbreak strains are well matched.1 Even with available licensed vaccines, up to 15% of the world’s population become infected with influenza every year, with as many as 5 million cases of severe illness and 500 000 deaths.2 In developed countries, most influenza deaths occur in elderly people, and, depending on the endpoint assessed, TIV effectiveness is as low as 9% in this population.

Articles
AS03-adjuvanted versus non-adjuvanted inactivated trivalent influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised trial
Janet E McElhaney, Jiri Beran, Jeanne-Marie Devaster, Meral Esen, Odile Launay, Geert Leroux-Roels, Guillermo M Ruiz-Palacios, Gerrit A van Essen, Adrian Caplanusi, Carine Claeys, Christelle Durand, Xavier Duval, Mohamed El Idrissi, Ann R Falsey, Gregory Feldman, Sharon E Frey, Florence Galtier, Shinn-Jang Hwang, Bruce L Innis, Martina Kovac, Peter Kremsner, Shelly McNeil, Andrzej Nowakowski, Jan Hendrik Richardus, Andrew Trofa, Lidia Oostvogels, for the Influence65 study group
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099%2813%2970046-X/abstract

Summary
Background
We aimed to compare AS03-adjuvanted inactivated trivalent influenza vaccine (TIV) with non-adjuvanted TIV for seasonal influenza prevention in elderly people.

Methods
We did a randomised trial in 15 countries worldwide during the 2008—09 (year 1) and 2009—10 (year 2) influenza seasons. Eligible participants aged at least 65 years who were not in hospital or bedridden and were without acute illness were randomly assigned (1:1) to receive either AS03-adjuvanted TIV or non-adjuvanted TIV. Randomisation was done in an internet-based system, with a blocking scheme and stratification by age (65—74 years and 75 years or older). Participants were scheduled to receive one vaccine in each year, and remained in the same group in years 1 and 2. Unmasked personnel prepared and gave the vaccines, but participants and individuals assessing any study endpoint were masked. The coprimary objectives were to assess the relative efficacy of the vaccines and lot-to-lot consistency of the AS03-adjuvanted TIV (to be reported elsewhere). For the first objective, the primary endpoint was relative efficacy of the vaccines for prevention of influenza A (excluding A H1N1 pdm09) or B, or both, that was confirmed by PCR analysis in year 1 (lower limit of two-sided 95% CI had to be greater than zero to establish superiority). From Nov 15, to April 30, in both years, participants were monitored by telephone or site contact and home visits every week or 2 weeks to identify cases of influenza-like illness. After onset of suspected cases, we obtained nasal and throat swabs to identify influenza RNA with real-time PCR. Efficacy analyses were done per protocol. This trial is registered with ClinicalTrials.gov, number NCT00753272.

Findings
We enrolled 43 802 participants, of whom 21 893 were assigned to and received the AS03-adjuvanted TIV and 21 802 the non-adjuvanted TIV in year 1. In the year 1 efficacy cohort, fewer participants given AS03-adjuvanted than non-adjuvanted TIV were infected with influenza A or B, or both (274 [1·27%, 95% CI 1·12—1·43] of 21 573 vs 310 [1·44%, 1·29—1·61] of 21 482; relative efficacy 12·11%, 95% CI −3·40 to 25·29; superiority not established). Fewer participants in the year 1 efficacy cohort given AS03-adjuvanted TIV than non-adjuvanted TIV were infected with influenza A (224 [1·04%, 95% CI 0·91—1·18] vs 270 [1·26, 1·11—1·41]; relative efficacy 17·53%, 95% CI 1·55—30·92) and influenza A H3N2 (170 [0·79, 0·67—0·92] vs 205 [0·95, 0·83—1·09]; post-hoc analysis relative efficacy 22·0%, 95% CI 5·68—35·49).

Interpretation
AS03-adjuvanted TIV has a higher efficacy for prevention of some subtypes of influenza than does a non-adjuvanted TIV. Future influenza vaccine studies in elderly people should be based on subtype or lineage-specific endpoints.

Funding
GlaxoSmithKline Biologicals SA.