A phase I randomized, double-blind, controlled trial of 2009 influenza A(H1N1) inactivated monovalent vaccines with different adjuvant systems

作者:Precioso Alexander R*; Miraglia Joao L; Campos Lucia Maria A; Goulart Alessandra C; Timenetsky Maria do Carmo S T; Cardoso Maria Regina A; Luna Expedito; Mondini Gabriella; Guedes Jose da S; Raw Isaias
来源:Vaccine, 2011, 29(48): 8974-8981.
DOI:10.1016/j.vaccine.2011.09.040

摘要

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 mu g of hemagglutinin antigen without adjuvant; 7.5 mu g of hemagglutinin antigen with aluminum hydroxide, MPL and squalene: 3.75 mu g of hemagglutinin antigen with aluminum hydroxide and MPL; and 3.75 mu g 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.

  • 出版日期2011-11-8