title: Innovative clinical trial designs to rationalize TB vaccine development.
abstract: A recent trial of a leading tuberculosis (TB) vaccine candidate in 3000 South African infants failed to show protection over that from BCG alone, and highlights the difficulties in clinical development of TB vaccines. Progression of vaccine candidates to efficacy trials against TB disease rests on demonstration of safety and immunogenicity in target populations and protection against challenge in preclinical models, but immunologic correlates of protection are unknown, and animal models may not be predictive of results in humans. Even in populations most heavily affected by TB the sample sizes required for Phase 2b efficacy trials using TB disease as an endpoint are in the thousands. Novel clinical trial models have been developed to evaluate candidate TB vaccines in selected populations using biologically relevant outcomes and innovative statistical approaches. Such proof of concept studies can be used to more rationally select vaccine candidates for advancement to large scale trials against TB disease.
authors: Aeras, 1405 Research Boulevard, Rockville, MD, USA. Electronic address: rellis@aeras.org.
authors: R D
authors: RD
authors: Ellis
authors: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease & Molecular Medicine (IDM), University of Cape Town, South Africa.
authors: M
authors: M
authors: Hatherill
authors: Aeras, Blackriver Park, First Floor, Old Warehouse Building, Observatory 7925, Cape Town, South Africa.
authors: D
authors: D
authors: Tait
authors: Aeras, 1405 Research Boulevard, Rockville, MD, USA.
authors: M
authors: M
authors: Snowden
authors: Aurum Institute, Johannesburg, Johannesburg, South Africa; School of Public Health, University of Witwatersrand, Johannesburg, South Africa.
authors: G
authors: G
authors: Churchyard
authors: Bill and Melinda Gates Foundation, Seattle, WA, USA.
authors: W
authors: W
authors: Hanekom
authors: Aeras, 1405 Research Boulevard, Rockville, MD, USA.
authors: T
authors: T
authors: Evans
authors: Aeras, 1405 Research Boulevard, Rockville, MD, USA.
authors: A M
authors: AM
authors: Ginsberg
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004059:Diffusion of Innovation; D055808:Drug Discovery / Q000639:trends*; D006801:Humans; D018579:Patient Selection; D012008:Recurrence; D012107:Research Design / Q000639:trends*; D012307:Risk Factors; D018401:Sample Size; D014376:Tuberculosis / Q000175:diagnosis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control* / Q000635:transmission; D032581:Tuberculosis Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D032581:Tuberculosis Vaccines
keywords: Clinical development; Prevention of infection; Prevention of recurrence; Proof of concept; Trial design; Tuberculosis; Vaccine