Evidence related to immunogenicity of Fluad® vaccine in adults (18 – 60 years) with or without comorbidities
Study	Vaccine	Study Design	Participants	Summary of Key Findings Using Text or Data	Level of Evidence	Quality
Baldo et al. Family Medicine Group of Pianiga. MF59-adjuvanted influenza vaccine confers superior immunogenicity in adult subjects (18-60 years of age) with chronic diseases who are at risk of post-influenza complications. Vaccine. 2007;25 (20):3955-61 (33).	Fluad® (MF59-adjuvanted subunit influenza vaccine; Sub/MF59) vs. Influpozzi Subunità® (non-adjuvanted subunit influenza vaccine; Sub) 0.5 ml IM; 15µg of each of the A/New Caledonia/20/99(H1N1); A/California/7/2004(H3N2); B/Shanghai/361/2002 strains	DB RCT; two-arm; parallel group; multi-center 2005-2006	238 adult subjects (18-60 years) with chronic diseases (cancer, diabetes, heart, lung) randomly assigned to Sub/MF59 (n=120) or Sub (n=118)	GMT, MFI, GMR, seroconversion rate, seroprotection rate from HI assay at 4 weeks post-vaccination Seroprotection (>70%): Sub/MF59 met for A/H1N1 and A/H3N2; Sub met for A/H1N1 only Sub/MF59 vs. Sub: A/H3N2: 75.0% vs. 57.6%, p=0.002 A/H1N1: 97.5% vs. 96.6%, NS B: 69.2% vs. 61.0%, NS Seroconversion (>40%): Sub/MF59 met for all 3 antigens; Sub met for A/H1N1 only Sub/MF59 vs. Sub: A/H3N2: 52.5% vs. 33.1%, p=0.02 A/H1N1: 57.5% vs. 55.9%, NS B: 46.7% vs. 36.4%, NS Post-vaccination GMT: Both Vaccines had significant increase in post-vaccination GMT against all 3 strains. Post-vaccination GMR: Sub/MF59 had significant higher GMT than Sub for A/H3N2 (p<0.001) and B (p<0.02) strains MFI (>2.5): Both vaccines met for all 3 antigens Addition of MF59 enhances the immunogenicity of subunit influenza vaccine in adults with chronic disease	I	Good
Durando et al. Safety and immunogenicity of two influenza virus subunit vaccines, with or without MF59 adjuvant, administered to human immunodeficiency virus type 1-seropositive and -seronegative adults. Clin Vaccine Immunol. 2008 ;15 (2):253-9 (34).	Fluad® (MF59-adjuvanted subunit influenza vaccine) vs. Agrippal® (non-adjuvanted subunit influenza vaccine) 0.5 ml IM; 15µg of each of the A/New Caledonia/20/99(H1N1); A/California/7/2004(H3N2); B/Shanghai/361/2002 strains	Open-label RCT; two-arm; parallel group; single-center 2005-2006	256 adult (18-65 years) with HIV-1-seronegative or HIV-1-seropositive randomly assigned to receive Fluad® (n=127) or Agrippal® (n=129) 4 groups: Fluad®, HIV-1(-) (n=81); Fluad®, HIV-1(+) (n=46); Agrippal®, HIV-1(-) (n=80); Agrippal®, HIV-1(+) (n=49)	GMT, GMR, seroconversion rate, seroprotection rate from HI assay at 4 weeks and 12 weeks post-vaccination Seroprotection (>70%): Both vaccines met for all 3 antigens. NS difference between groups Seroconversion (>40%): Both vaccines met for all 3 antigens. NS difference between groups Post-vaccination GMT: After Beyer’s correction, Fluad® had significant higher GMT than Agrippal for all influenza vaccine subtypes, although statistical significant was reached for only AH1N1 (p=0.005) and B (p=0.023) strains in HIV-1-seronegative subjects; for seropositive subjects, Fluad had significantly higher GMT than Agrippal for A/H3N2 (p=0.003) strain only in HIV-1-seropositive subjects. A value near significance was observed for A/H1N1 strain in seropositive subjects (p=0.097) Both vaccines had good immunogenicity for both uninfected and HIV-1-infected adults. No definitive conclusions could be drawn for the superiority of Fluad® over Agrippal.	I	Poor (small sample size; method of randomization not reported)
Frey et al. Comparison of the safety, tolerability, and immunogenicity of a MF59-adjuvanted influenza vaccine and a non-adjuvanted influenza vaccine in non-elderly adults. Vaccine. 2003;21(27-30):4234-7 (35).	Fluad® (MF59-adjuvanted subunit influenza vaccine) vs. Fluzone™ (non-adjuvanted subunit influenza vaccine) 0.5 ml IM; 15µg of each of the A/Texas/39/91(H1N1); A/Johannesburg/33/94(H3N2); B/Harbin/7/94 strains (1st immunization) and A/Texas/39/91(H1N1); A/Nanchang/933/95(H3N2); B/Harbin/7/94 strains (2nd immunization)	Observer-blind RCT; two-arm; parallel group; multi-center 1995-1996 Study extension for a subsequent injection in year 2: 1996-1997	301 healthy adult subjects (18-64 years) randomly assigned to receive Fluad® (n=150) or Fluzone™ (n=151) Year 2: Fluad (n=99) Fluzone (n=94)	GMT, seroconversion rate, seroprotection rate from HI assay at 4 weeks post-vaccination and 180 days post-vaccination Seroprotection (>70%): Both vaccines met for all 3 antigens. NS difference between groups Seroconversion (>40%): Both vaccines met for all 3 antigens. Significant difference reached for B strain (Fluad®: 83% vs. Fluzone: 71%, p=0.008) Post-vaccination GMT: NS difference between groups Year 2: 28 days post-injection Seroprotection: Significant difference reached for A/H3N2 strain (Fluad 53% vs Fluzone 26%, p<0.0001) Seroconversion: Significant difference reached for A/H3N2 strain (Fluad® 55% vs. Fluzone 32%, p≤0.0005) Post-vaccination GMT: GMT higher for H3N2 strain in Fluad vs Fluzone (112 vs. 71, p≤0.001) No significant differences were seen at day 180 except in the % of subjects with a titer: 160 for A/H1N1 antigen (Fluad 57% vs Fluzone 73%, p=0.025) Fluad was slightly more immunogenic in healthy adults for the B strain after the 1st injection and for the A/H3N2 strain after the 2nd injection.	I	Poor (method of randomization not reported; not followed up for AEs)
Gabutti et al. Safety and immunogenicity of conventional subunit and MF59-adjuvanted influenza vaccines in human immunodeficiency virus-1-seropositive patients. J Int Med Res. 2005 ;33 (4):406-16 (36).	Fluad® (MF59-adjuvanted subunit influenza vaccine) vs. Agrippal® (non-adjuvanted subunit influenza vaccine) 0.5 ml IM; 15µg of each of the A/New Caledonia/20/99(H1N1); A/Moscow/10/99(H3N2); B/Hong Kong/330/2001 strains	RCT; two-arm; parallel group; single-center 2002-2003	37 adult subjects (18-65 years) with HIV-1-seropositive randomly assigned to receive Fluad® (n=18) or Agrippal® (n=19)	GMT, GMR, seroconversion rate, seroprotection rate from HI assay at 4 weeks post-vaccination and 180 days post-vaccination Seroprotection (>70%): Both vaccines met for all 3 antigens. NS difference between groups Seroconversion (>40%): Both vaccines met for all 3 antigens. NS difference between groups Post-vaccination GMT: NS difference between groups Both Fluad and Agrippal were immunogenic, and there was prolonged persistence of antibodies towards all 3 strains after 180 days.	I	Poor (small sample size; method of randomization not reported