A phase I randomized, double-blind, controlled trial of 2009 influenza A (H1N1) inactivated monovalent vaccines with different adjuvant systems.
Author(s): Precioso AR, Miraglia JL, Campos LM, Goulart AC, Timenetsky Mdo C, Cardoso MR, Luna E, Mondini G, Guedes Jda S, Raw I
Affiliation(s): Butantan Institute/Butantan Foundation, Clinical Trials Unit, Sao Paulo, Brazil. firstname.lastname@example.org
Publication date & source: 2011-11-08, Vaccine., 29(48):8974-81. Epub 2011 Sep 21.
Publication type: Research Support, Non-U.S. Gov't
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 mug of hemagglutinin antigen without adjuvant; 7.5 mug of hemagglutinin antigen with aluminum hydroxide, MPL and squalene; 3.75 mug of hemagglutinin antigen with aluminum hydroxide and MPL; and 3.75 mug 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. Copyright (c) 2011 Elsevier Ltd. All rights reserved.