Abstract

Tuberculosis (TB) remains a major cause of illness and death worldwide, making a new TB vaccine an urgent public health priority. Purified protein derivative (PPD)-negative adults ( n = 50) were equally randomized to receive 3 doses at 1-month intervals (at 0, 1, and 2 months) of one of the following vaccines: Mtb72F/AS02 A (10 or 40 µg antigen), Mtb72F/saline (10 or 40 µg antigen), or AS02 A . Mtb72F/AS02 A recipients received an additional dose 1 year after the first dose to evaluate if the elicited immune response could be boosted. Mtb72F/AS02 A vaccines were locally reactogenic but clinically well tolerated, with transient adverse events (usually lasting between 1 and 4 days) that resolved without sequelae being observed. No vaccine-related serious adverse events were reported. Vaccination with Mtb72F/AS02 A induced a strong Mtb72F-specific humoral response and a robust Mtb72F-specific CD4 + T-cell response, both of which persisted at 9 months after primary immunization and for 1 year after the booster immunization. There was no significant difference between the magnitude of the CD4 + T-cell response induced by the 10-µg and 40-µg Mtb72F/AS02 A vaccines. The Mtb72F-specific CD4 + T cells predominantly expressed CD40L; CD40L and interleukin-2 (IL-2); CD40L and tumor necrosis factor alpha (TNF- ); CD40L, IL-2, and TNF- ; and CD40L, IL-2, TNF- , and gamma interferon (IFN- ). Serum IFN- , but not TNF- , was detected 1 day after doses 2 and 3 for the Mtb72F/AS02 A vaccine but did not persist. Vaccine-induced CD8 + T-cell responses were not detected, and no immune responses were elicited with AS02 A alone. In conclusion, Mtb72F/AS02 A is clinically well tolerated and is highly immunogenic in TB-naïve adults. The 10- and 40-µg Mtb72F/AS02 A vaccines show comparable safety and immunogenicity profiles.