The H1 recombinant fusion protein of Ag85B and ESAT-6, is developed and manufactured by Statens Serum Institut (SSI, Copenhagen, Denmark). H1 sterile solution and CAF01 sterile suspension were manufactured by SSI, in an accredited
GMP facility and supplied to the LUMC pharmacy in separate vials of relevant strengths. The vaccine was reconstituted by addition of the specified volume of adjuvant to the antigen concentrate, and injected into the deltoid muscle with a 25 mm 22–25 Gauge needle in a volume of 0.5 ml. The trial was an open label, single-center, non-randomized phase I exploratory trial in mycobacteria-naïve individuals defined by a negative TST (<10 mm, 2 units RT-23 PPD (SSI, Denmark)) and a negative Quantiferon®-TB Gold In-Tube test (QFT; Qiagen, Venlo, The Netherlands). All individuals were HIV negative. The trial comprised four vaccination groups. Subjects in group 1 received 50 μg H1 with no adjuvant, whereas groups CT99021 chemical structure 2–4 received the same amount of antigen with 125/25 μg, 313/63 μg and 625/125 μg
CAF01, respectively. In all vaccination groups, the subjects were vaccinated on trial days 0 and 56. After Saracatinib the original trial was completed, a protocol amendment was approved (CCMO 12.1306/MA/26270, NL26270.000.09) and all trial participants were invited to attend a long-term visit 150 weeks after initial enrolment. Long-term visits were successfully conducted for 31 out of the original 34 volunteers that received
2 vaccinations within the appropriate time window. Timing of the long-term visit was on average 150.7 weeks (median 152.1 weeks; range 123–167 weeks) post primary vaccination and is referred to as ‘150 weeks’ throughout the manuscript. The trial population consisted of 38 volunteers, healthy adult females or males between 18 and 55 years of age who had not been BCG vaccinated and who did not have active, chronic or past TB disease, and who had no MTB infection as confirmed by a negative QFT and a negative TST at screening. The general health of all participants was assessed by reviewing their recorded medical history, and performing a physical examination, and standard blood (including hepatitis B, hepatitis C and HIV testing) and urine tests. The volunteers were financially compensated as approved by the Institutional Review Board for the Non-specific serine/threonine protein kinase number and amount of blood and urine samples, inconvenience with respect to the intramuscular administration and for the time spent on trial visits and transportation to the trial site. The subjects remained under medical observation for 3 h after each intramuscular vaccination, for possible immediate adverse reactions. During the first week after each vaccination, symptoms and evening armpit temperature were recorded on a daily basis, thereafter on a weekly basis. A medical examination of local adverse reactions and temperature was performed on days 0, 1, 7 and 42 after both vaccinations.