Influenza symptoms and their impact on elderly adults: randomised trial of AS03‐adjuvanted or non‐adjuvanted inactivated trivalent seasonal influenza vaccines

Abstract

BackgroundPatient-reported outcomes (PROs) are particularly relevant in influenza vaccine trials in the elderly where reduction in symptom severity could prevent illness-related functional impairment.ObjectivesTo evaluate PROs in people aged ≥65 years receiving two different vaccines.MethodsThis was a phase III, randomised, observer-blind study (NCT00753272) of the AS03-adjuvanted inactivated trivalent split-virion influenza vaccine (AS03-TIV) versus non-adjuvanted vaccine (TIV). Using the FluiiQ questionnaire, symptom (systemic, respiratory, total) and life impact (activities, emotions, relationships) scores were computed as exploratory endpoints, with minimal important difference (MID) in influenza severity between vaccines considered post-hoc as >7%. Vaccine efficacy of AS03-TIV relative to TIV in severe influenza (hospitalisation, complication, most severe one-third of episodes based on the area under the curve for systemic symptom score) was calculated post-hoc. The main analyses (descriptive) were conducted in the according-to-protocol cohort (n = 280 AS03-TIV, n = 315 TIV) for influenza confirmed by culture or reverse transcriptase polymerase chain reaction.ResultsMean systemic symptom, total symptom and impact on activities scores were lower with AS03-TIV versus TIV. Mean respiratory symptom, impact on emotions and impact on relationships scores were similar. Influenza tended to be less severe with AS03-TIV, but the MID was reached only for impact on activities (mean 9·0%). Relative vaccine efficacy in severe influenza was 29·38% (95% CI: 7·60–46·02).ConclusionsAS03-TIV had advantages over TIV in impact on systemic symptoms and activities as measured by the FluiiQ in elderly people. Higher efficacy of AS03-TIV relative to TIV was shown for prevention of severe illness.

Effect of Antihelminthic Treatment on Vaccine Immunogenicity to a Seasonal Influenza Vaccine in Primary School Children in Gabon: A Randomized Placebo-Controlled Trial

“…Vaccination is one of the most effective tools to prevent infectious diseases. Nonetheless seroconversion and therefore efficacy are variable in vaccinated individuals depending on age, environment and genetic host factors[ 16 – 18 ]. In addition, acute and chronic infections have an influence on vaccine outcome[ 19 , 20 ].…”

Impact of age and pre-existing influenza immune responses in humans receiving split inactivated influenza vaccine on the induction of the breadth of antibodies to influenza A strains

“…Influenza vaccination is less effective in the elderly compared to young adults, in part due to decreased generation of specific serum antibodies [ 13 ] [ 14 ] [ 15 ] [ 16 ] [ 17 ] [ 18 ] switched memory B cells [ 19 ] [ 13 ] [ 14 ] [ 15 ] [ 17 ] [ 18 ], and the presence of long-lived plasma cells (PC) [ 20 ] [ 21 ] [ 22 ]. Moreover, antibody titers generated in response to a booster vaccination depend on B cell stimulation, differentiation to B memory cells generated during the primary response, and stimulation and differentiation of these to make new plasmablasts and PC [ 23 ].…”

B Cell–Specific Biomarkers for Optimal Antibody Responses to Influenza Vaccination and Molecular Pathways That Reduce B Cell Function with Aging

“…Antibody responses represent the gold standard of influenza vaccine efficacy, which is reduced in the elderly in part because of decreased generation of specific serum antibodies, 41–46 switched-memory B cells, 42,43,47–49 and long-lived plasma cells. 50,51 …”