• Jaime Montoya, Juan Antonio Solon, Soledad Rosanna C Cunanan, Luz Acosta, Anne Bollaerts, Philippe Moris, Michel Janssens, Erik Jongert, Marie-Ange Demoitié, Pascal Mettens, Salvacion Gatchalian, Carlota Vinals, Joe Cohen, and Opokua Ofori-Anyinam.
• Section of Infectious Diseases, Department of Medicine, University of the Philippines College of Medicine, 547 Pedro Gil Street, Ermita, Manila, 1000, Philippines.
• J. Clin. Immunol. 2013 Nov 1;33(8):1360-75.

PurposeIn this dose-finding Phase II study (NCT00621322), we evaluated the safety and immunogenicity of different formulations of the candidate tuberculosis vaccine containing the M72 antigen (10/20/40 μg doses) and the liposome-based AS01 Adjuvant System. We aimed to select the lowest-dose combination of M72 and AS01 that was clinically well tolerated with immunogenicity comparable to that of the previously tested M72/AS01B (40 μg) candidate vaccine.MethodsHealthy PPD-positive (induration 3-10 mm) adults (18-45 years) in The Philippines were randomized (4:4:4:4:1:1) to receive 2 injections, 1 month apart, of M72/AS01B (40 μg), M72/AS01E (10 μg), M72/AS01E (20 μg), M72/AS02D (10 μg), M72/Saline (40 μg) or AS01B alone, and were followed up for 6 months. AS01E and AS02D contain half the quantities of the immunostimulants present in AS01B. AS02D is an oil-in-water emulsion. Vaccine selection was based on the CD4(+) T-cell responses at 1 month post vaccination.ResultsAll formulations had a clinically acceptable safety profile with no vaccine-related serious adverse events reported. Two vaccinations of each adjuvanted M72 vaccine induced M72-specific CD4(+) T-cell and humoral responses persisting at 6 months post vaccination. No responses were observed with AS01B alone. One month post second vaccination, CD4(+) T-cell responses induced by each of the three M72/AS01 vaccine formulations were of comparable magnitudes, and all were significantly higher than those induced by M72/AS02D (10 μg) and M72/Saline.ConclusionsThe formulation with the lowest antigen and adjuvant dose, M72/AS01E (10 μg), fulfilled our pre-defined selection criteria and has been selected for further clinical development.

25 keywords...

hide…