A phase I, open-label trial on the safety and immunogenicity of the adjuvanted tuberculosis subunit vaccine H1/IC31? in people living in a TB-endemic area

摘要

H1/IC31? is a tuberculosis (TB) subunit vaccine candidate consisting of the fusion protein of Ag85B and ESAT-6 (H1) formulated with the IC31? adjuvant. Previous trials have reported on the H1/IC31? vaccine in M. tuberculosis (Mtb)-na?ve, BCG-vaccinated and previously Mtb-infected individuals. In this trial, conducted between December 2008 and April 2010, the safety and immunogenicity of H1/IC31? was assessed in participants living in Ethiopia – a highly TB-endemic area. Healthy male participants aged 18–25 years were recruited into four groups. Participants in group 1 (N?=?12) and group 2 (N?=?12) were Tuberculin Skin Test (TST) negative and QuantiFERON-TB Gold in-tube test (QFT) negative (Mtb-na?ve groups), participants in group 3 (N?=?3) were TST positive and QFT negative (BCG group), and participants in group 4 (N?=?12) were both TST and QFT positive (Mtb-infected group). H1 vaccine alone (group 1) or H1 formulated with the adjuvant IC31? (groups 2, 3 and 4) was administered intramuscularly on day 0 and day 56. Safety and immunogenicity parameters were evaluated for up to 32?weeks after day 0. The H1/IC31?vaccine was safe and generally well tolerated. There was little difference among the four groups, with a tendency towards a higher incidence of adverse events in Mtb-infected compared to Mtb-na?ve participants. Two serious adverse events were reported in the Mtb-infected group where a relationship to the vaccine could not be excluded. In both cases the participants recovered without sequelae within 72?h. Immunogenicity assays, evaluated in the 29 participants who received both vaccinations, showed a stronger response to TB antigens in the Mtb-na?ve group vaccinated with the adjuvant. The trial confirmed the need for an adjuvant for the vaccine to be immunogenic and highlighted the importance of early phase testing of a novel TB vaccine candidate in TB-endemic areas. ClinicalTrials.gov, ID: NCT01049282. Retrospectively registered on 14 January 2010.