title: First in humans: a new molecularly defined vaccine shows excellent safety and strong induction of long-lived Mycobacterium tuberculosis-specific Th1-cell like responses.
abstract: Tuberculosis (TB) remains a major killer worldwide. The only available TB-vaccine, the nearly century-old Mycobacterium bovis BCG, has had only a limited effect on TB incidence. Therefore, developing new TB vaccines is a key priority, and the first new generation TB vaccines are now being tested in clinical trials. Here we describe the development and first testing in humans of a novel, wholly synthetic TB subunit vaccine. This vaccine has proven safe and highly immunogenic in all species in which it was tested, including mice, guinea pigs, non-human primates and humans. Most encouragingly, following vaccination in humans, strong IFN-γ responses persisted through at least 2½ years of follow-up, indicating induction of a substantial memory response by this new TB vaccine. These findings encourage further preclinical and clinical studies with TB subunit vaccines and cellular immunity-stimulating new adjuvants.
authors.affiliation: Leiden University Medical Center, Dept. of Infectious Diseases, Leiden, The Netherlands. t.h.m.ottenhoff@lumc.nl
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: T Mark
authors.initials: TM
authors.lastname: Doherty
authors.forename: Jaap T
authors.initials: JT
authors.lastname: van Dissel
authors.forename: Peter
authors.initials: P
authors.lastname: Bang
authors.forename: Karen
authors.initials: K
authors.lastname: Lingnau
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kromann
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
mesh_terms: D000818:Animals; D006168:Guinea Pigs; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D013997:Time Factors; D032581:Tuberculosis Vaccines / Q000009:adverse effects* / Q000737:chemistry / Q000276:immunology*; D022223:Vaccines, Subunit / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000737:chemistry / Q000276:immunology
chemical_list: D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D007371:Interferon-gamma