title: A phase II study of an investigational tetravalent influenza vaccine formulation combining MF59®: adjuvanted, pre-pandemic, A/H5N1 vaccine and trivalent seasonal influenza vaccine in healthy adults.
abstract: An investigational tetravalent vaccine combining pre-pandemic, MF59®-adjuvanted A/H5N1 vaccine with non-adjuvanted, trivalent, seasonal influenza vaccine has been developed, which has the potential to be used for pre-pandemic priming and to improve levels of compliance and coverage. It is important to determine whether the safety and immunogenicity of the combination vaccine is equivalent to that of the two separate vaccines when administered concomitantly. Healthy adults (n=601) were randomly assigned to three vaccination groups to receive either: (1) tetravalent vaccine and placebo concomitantly (in separate arms) on Day 1, followed by A/H5N1 vaccine on Day 22; (2) A/H5N1 vaccine and placebo concomitantly on Day 1, followed by tetravalent vaccine on Day 22; or (3) A/H5N1 and seasonal vaccines concomitantly on Day 1, followed by A/H5N1 vaccine on Day 22. Antibody responses were measured using single radial hemolysis (SRH), haemagglutination inhibition (HI), and microneutralization (MN) assays on Days 1, 22, and 43. Solicited adverse reactions were recorded for seven days after vaccination. Spontaneous adverse events were recorded throughout the study. The tetravalent vaccine elicited antibody titers equivalent to those for separate A/H5N1 and seasonal vaccines, and sufficient to meet the European licensure criteria against A/H5N1 and all three seasonal strains. Local and systemic reactions were mainly mild to moderate. No vaccine-related serious adverse events occurred. These findings demonstrate that MF59-adjuvanted A/H5N1 and seasonal influenza vaccines had an acceptable safety profile and could be effectively administered as a tetravalent formulation, supporting the possibility of integrating pre-pandemic priming into seasonal influenza vaccination programs.
authors.affiliation: Department of Infectious Diseases and Tropical Medicine; University Hospital; Ludwig-Maximilians-Universität München; Munich, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Herbinger
authors.affiliation: Department of Infectious Diseases and Tropical Medicine; University Hospital; Ludwig-Maximilians-Universität München; Munich, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: von Sonnenburg
authors.affiliation: Department of Infectious Diseases and Tropical Medicine; University Hospital; Ludwig-Maximilians-Universität München; Munich, Germany.
authors.forename: Hans Dieter
authors.initials: HD
authors.lastname: Nothdurft
authors.affiliation: Department of Infectious Diseases and Tropical Medicine; University Hospital; Ludwig-Maximilians-Universität München; Munich, Germany.
authors.forename: Pamela
authors.initials: P
authors.lastname: Perona
authors.affiliation: Novartis Vaccines & Diagnostics; Cambridge, MA USA.
authors.forename: Astrid
authors.initials: A
authors.lastname: Borkowski
authors.affiliation: Novartis Vaccines & Diagnostics; Cambridge, MA USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Fragapane
authors.affiliation: Novartis Vaccines & Diagnostics; Cambridge, MA USA.
authors.forename: Uwe
authors.initials: U
authors.lastname: Nicolay
authors.affiliation: Novartis Vaccines & Diagnostics; Cambridge, MA USA.
authors.forename: Ralf
authors.initials: R
authors.lastname: Clemens
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000914:Antibodies, Viral / Q000097:blood; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D064368:Healthy Volunteers; D006385:Hemagglutination Inhibition Tests; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D009500:Neutralization Tests; D011136:Polysorbates / Q000008:administration & dosage / Q000009:adverse effects; D013185:Squalene / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene
keywords: H5N1; MF59; influenza vaccine; pandemic; seasonal influenza
references.citation: Scand J Infect Dis. 2011 Sep;43(9):702-6
references.pmid: 21534891
references.citation: N Engl J Med. 2009 Jun 18;360(25):2667-8
references.pmid: 19423870
references.citation: Expert Rev Vaccines. 2012 Aug;11(8):1009-19
references.pmid: 23002981
references.citation: Lancet. 2001 Jun 16;357(9272):1937-43
references.pmid: 11425416
references.citation: Cell Res. 2010 Jan;20(1):51-61
references.pmid: 19884910
references.citation: Sci Transl Med. 2010 Jan 20;2(15):15ra5
references.pmid: 20371470
references.citation: Vaccine. 2008 Jun 19;26(26):3209-22
references.pmid: 18462843
references.citation: Clin Vaccine Immunol. 2010 Nov;17(11):1817-9
references.pmid: 20810680
references.citation: Sci Transl Med. 2011 Jun 1;3(85):85ra48
references.pmid: 21632986
references.citation: Scand J Infect Dis. 2011 Dec;43(11-12):993
references.pmid: 21851329
references.citation: Int J Clin Pract. 2010 Mar;64(4):432-8
references.pmid: 20039974
references.citation: Vaccine. 2003 Apr 2;21(15):1687-93
references.pmid: 12639491
references.citation: Lancet. 2010 Jan 2;375(9708):6-9
references.pmid: 20018366
references.citation: Lancet. 2007 Aug 18;370(9587):580-9
references.pmid: 17707753
references.citation: Nature. 2010 May 13;465(7295):161
references.pmid: 20463719
references.citation: Vaccine. 2009 Nov 16;27(49):6959-65
references.pmid: 19751689
references.citation: Lancet Infect Dis. 2008 Oct;8(10):650-8
references.pmid: 18922487
references.citation: PLoS One. 2009;4(2):e4384
references.pmid: 19197383
references.citation: Science. 2012 Jun 22;336(6088):1534-41
references.pmid: 22723413
references.citation: Science. 2012 Jun 22;336(6088):1541-7
references.pmid: 22723414
references.citation: Nature. 2006 Jul 27;442(7101):448-52
references.pmid: 16642006
references.citation: Lancet. 2010 Jan 2;375(9708):49-55
references.pmid: 20018367
references.citation: N Engl J Med. 2010 May 6;362(18):1708-19
references.pmid: 20445182
references.citation: PLoS One. 2011;6(9):e24384
references.pmid: 21915319
references.citation: N Engl J Med. 2006 Mar 30;354(13):1343-51
references.pmid: 16571878
references.citation: J Infect Dis. 2011 Jun 15;203(12):1719-28
references.pmid: 21606530