Selection of an adjuvant for seasonal influenza vaccine in elderly people: modelling immunogenicity from a randomized trial

BMC Infectious Diseases

Lidia Oostvogels⁶  Walthère Dewé⁷  Jeanne-Marie Devaster⁶  Christelle Durand⁷  Georg Plaßmann⁴  Karlis Pauksens¹  Lars Rombo²  Jan Hendrik Richardus³  Hans C Rümke⁵ 

[1] Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden;Clinical research centre Sormland, Uppsala University, Uppsala, Sweden;Senior Investigator, Department of Infectious Disease Control, Municipal Public Health Service (GGD) Rotterdam-Rijnmond, Rotterdam, The Netherlands;Unterfrintroper Hausarztzentrum, Unterstraße 75, 45359, Essen, Germany;Medical Director, Vaxinostics, University Vaccine Center, Rotterdam, The Netherlands;Vaccine Discovery and Development, GlaxoSmithKline Vaccines, Wavre, Belgium;Vaccine Value & Health Science, GlaxoSmithKline Vaccines, Wavre, Belgium

关键词: Safety;    Reactogenicity;    Immunogenicity;    Dose comparison;    Adjuvant system;    Elderly;    Influenza vaccination;   

Others  :  1146636
DOI  :  10.1186/1471-2334-13-348

 received in 2012-11-30, accepted in 2013-07-18,  发布年份 2013

【 摘 要 】

Background

Improved influenza vaccines are needed to reduce influenza-associated complications in older adults. The aim of this study was to identify the optimal formulation of adjuvanted seasonal influenza vaccine for use in elderly people.

Methods

This observer-blind, randomized study assessed the optimal formulation of adjuvanted seasonal influenza vaccine based on immunogenicity and safety in participants aged ≥65 years. Participants were randomized (~200 per group) to receive one dose of non-adjuvanted vaccine or one of eight formulations of vaccine formulated with a squalene and tocopherol oil-in-water emulsion-based Adjuvant System (AS03_C, AS03_B or AS03_A, with 2.97, 5.93 and 11.86 mg tocopherol, respectively) together with the immunostimulant monophosphoryl lipid A (MPL, doses of 0, 25 or 50 mg). Hemagglutination-inhibition (HI) antibody responses and T-cell responses were assessed on Day 0 and 21 days post-vaccination. The ratio of HI-based geometric mean titers in adjuvanted versus non-adjuvanted vaccine groups were calculated and the lower limit of the 90% confidence interval was transformed into a desirability index (a value between 0 and 1) in an experimental domain for each vaccine strain, and plotted in relation to the AS03 and MPL dose combination in the formulation. This model was used to assess the optimal formulation based on HI antibody titers. Reactogenicity and safety were also assessed. The immunogenicity and safety analyses were used to evaluate the optimal formulation of adjuvanted vaccine.

Results

In the HI antibody-based model, an AS03 dose–response was evident; responses against the A/H1N1 and A/H3N2 strains were higher for all adjuvanted formulations versus non-adjuvanted vaccine, and for the AS03_A-MPL25, AS03_B-MPL25 and AS03_B-MPL50 formulations against the B strain. Modelling using more stringent criteria (post hoc) showed a clear dose-range effect for the AS03 component against all strains, whereas MPL showed a limited effect. Higher T-cell responses for adjuvanted versus non-adjuvanted vaccine were observed for all except two formulations (AS03_C and AS03_B-MPL25). Reactogenicity increased with increasing AS03 dosage, and with MPL. No safety concerns were raised.

Conclusions

Five formulations containing AS03_A or AS03_B were identified as potential candidates to improve immune responses to influenza vaccination; AS03_B without MPL showed the best balance between improved immunogenicity and acceptable reactogenicity.

Trial registration

This trial is registered at ClinicalTrials.gov, NCT00540592

【 授权许可】

   
2013 Rümke et al.; licensee BioMed Central Ltd.

【 图 表 】

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