title: A phase I randomized, double-blind, controlled trial of 2009 influenza A (H1N1) inactivated monovalent vaccines with different adjuvant systems.
abstract: METHODS
  We conducted a phase I, multicenter, randomized, double-blind, placebo-controlled, multi-arm (10) parallel study involving healthy adults to evaluate the safety and immunogenicity of influenza A (H1N1) 2009 non-adjuvanted and adjuvanted candidate vaccines. Subjects received two intramuscular injections of one of the candidate vaccines administered 21 days apart. Antibody responses were measured by means of hemagglutination-inhibition assay before and 21 days after each vaccination. The three co-primary immunogenicity end points were the proportion of seroprotection >70%, seroconversion >40%, and the factor increase in the geometric mean titer >2.5.
  
  
  RESULTS
  A total of 266 participants were enrolled into the study. No deaths or serious adverse events were reported. The most commonly solicited local and systemic adverse events were injection-site pain and headache, respectively. Only three subjects (1.1%) reported severe injection-site pain. Four 2009 influenza A (H1N1) inactivated monovalent candidate vaccines that met the three requirements to evaluate influenza protection, after a single dose, were identified: 15 μg of hemagglutinin antigen without adjuvant; 7.5 μg of hemagglutinin antigen with aluminum hydroxide, MPL and squalene; 3.75 μg of hemagglutinin antigen with aluminum hydroxide and MPL; and 3.75 μg of hemagglutinin antigen with aluminum hydroxide and squalene.
  
  
  CONCLUSIONS
  Adjuvant systems can be safely used in influenza vaccines, including the adjuvant monophosphoryl lipid A (MPL) derived from Bordetella pertussis with squalene and aluminum hydroxide, MPL with aluminum hydroxide, and squalene and aluminum hydroxide.
authors.affiliation: Butantan Institute/Butantan Foundation, Clinical Trials Unit, São Paulo, Brazil. alexrp@butantan.gov.br
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Precioso
authors.forename: João L
authors.initials: JL
authors.lastname: Miraglia
authors.forename: Lúcia Maria A
authors.initials: LM
authors.lastname: Campos
authors.forename: Alessandra C
authors.initials: AC
authors.lastname: Goulart
authors.forename: Maria do Carmo S T
authors.initials: Mdo C
authors.lastname: Timenetsky
authors.forename: Maria Regina A
authors.initials: MR
authors.lastname: Cardoso
authors.forename: Expedito
authors.initials: E
authors.lastname: Luna
authors.forename: Gabriella
authors.initials: G
authors.lastname: Mondini
authors.forename: José da S
authors.initials: Jda S
authors.lastname: Guedes
authors.forename: Isaias
authors.initials: I
authors.lastname: Raw
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000536:Aluminum Hydroxide / Q000008:administration & dosage; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D004311:Double-Blind Method; D005260:Female; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D007251:Influenza, Human / Q000517:prevention & control*; D007273:Injections, Intramuscular; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives; D008297:Male; D013185:Squalene / Q000008:administration & dosage; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D008050:Lipid A; D015164:Vaccines, Inactivated; D000536:Aluminum Hydroxide; D013185:Squalene; C048436:monophosphoryl lipid A