ABSTRACT: BACKGROUND: The safety and immunogenicity of an MF59trade mark-adjuvanted subunit influenza vaccine (Sub/MF59trade mark; FLUAD(R), Novartis Vaccines) was evaluated among elderly Chinese subjects (>/= 60 years of age). After a preliminary Phase I, open-label study (n = 25) to assess safety 1-14 days post-vaccination, a comparative observer-blind, randomised, controlled clinical trial (n = 600) was performed to assess safety and immunogenicity versus a non-adjuvanted subunit influenza vaccine (Subunit; Agrippal(R), Novartis Vaccines). Subjects were randomised (2:1) to receive Sub/MF59trade mark or Subunit. RESULTS: Both vaccines were well tolerated, with no vaccine-related serious adverse events reported during the Phase I trial. During the observer-blind study, local and systemic reactions were generally similar for both vaccines 1-22 days post-vaccination; however, injection-site induration was more frequent among the Subunit group (P < 0.05), and mild pain at the injection site and fever were more frequent among Sub/MF59trade mark recipients (P </= 0.005). Both vaccines induced a significant (P < 0.001) increase in geometric mean titres (GMTs) for the three strains tested, versus baseline; GMTs against A/H1N1, A/H3N2 and B were significantly higher in the Sub/MF59trade mark group (P = 0.034, P < 0.001 and P = 0.005, respectively). GMT ratios against A/H1N1, A/H3N2 and B were also significantly higher in the Sub/MF59trade mark group (P = 0.038, P < 0.001 and P = 0.006, respectively). Similarly, the percentage of subjects achieving seroprotection or seroconversion on Day 22 was greater for Sub/MF59trade mark recipients, reaching significance for A/H3N2 (P < 0.001). CONCLUSION: MF59trade mark-adjuvanted subunit influenza vaccine is well tolerated by elderly Chinese subjects and induces a higher level of immunogenicity than a non-adjuvanted subunit influenza vaccine in this population that is at high risk of influenza-related complications. CLINICAL TRIAL REGISTRY: http://www.clinicaltrials.gov, NCT00310648.