A recombinant uncleaved clade C HIV-1 envelope gp140 protein (CN54gp140) produced by Polymun Scientific (Klosterneuburg, Austria) to GMP specification, which has previously been reported to be immunogenic in a number of preclinical and clinical studies (26 (link), 27 (link)), was used for the X001 clinical trial. The vaccine Ag CN54gp140 was administered intramuscularly into the deltoid muscle of the upper arm at a dosage of 100 µg CN54gp140 formulated with 5 µg GLA-AF [Infectious Disease Research Institute, Seattle, WA, USA (28 (link))] in a total volume of 0.4 ml. GLA has been shown to enhance antibody responses in mice, non-human primates, and humans without causing adverse reactions (29 (link), 30 (link)). Good adjuvanticity was observed in a previous influenza clinical trial where they used 2.5 µg GLA and a clinical trial of a leishmaniasis vaccine using 2 or 5 µg GLA in an oil-in-water emulsion formulation (GLA-SE), which was safe and well tolerated (30 (link), 31 (link)). Since much of the reactogenicity of GLA-SE is believed to be associated with its oil-in-water form, the aqueous formulation GLA-AF was assumed to be less reactogenic. Subsequent animal studies revealed that GLA-AF has broadly equivalent adjuvant activity to GLA-SE and based on these findings for the current trial a 5-µg dose of GLA was selected (32 (link)). Further, good tolerability of GLA-AF at a dose of 5 µg in combination with the CN54gp140 Ag has been demonstrated in previous clinical trials conducted by us (27 (link), 33 (link)).
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