title: Tuberculosis vaccines and prevention of infection.
abstract: Tuberculosis (TB) is a leading cause of death worldwide despite the availability of effective chemotherapy for over 60 years. Although Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination protects against active TB disease in some populations, its efficacy is suboptimal. Development of an effective TB vaccine is a top global priority that has been hampered by an incomplete understanding of protective immunity to TB. Thus far, preventing TB disease, rather than infection, has been the primary target for vaccine development. Several areas of research highlight the importance of including preinfection vaccines in the development pipeline. First, epidemiology and mathematical modeling studies indicate that a preinfection vaccine would have a high population-level impact for control of TB disease. Second, immunology studies support the rationale for targeting prevention of infection, with evidence that host responses may be more effective during acute infection than during chronic infection. Third, natural history studies indicate that resistance to TB infection occurs in a small percentage of the population. Fourth, case-control studies of BCG indicate that it may provide protection from infection. Fifth, prevention-of-infection trials would have smaller sample sizes and a shorter duration than disease prevention trials and would enable opportunities to search for correlates of immunity as well as serve as a criterion for selecting a vaccine product for testing in a larger TB disease prevention trial. Together, these points support expanding the focus of TB vaccine development efforts to include prevention of infection as a primary goal along with vaccines or other interventions that reduce the rate of transmission and reactivation.
authors.affiliation: Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA thawn@u.washington.edu.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Hawn
authors.affiliation: HIV Vaccine Trials Network, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Day
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
authors.forename: Mark
authors.initials: M
authors.lastname: Hatherill
authors.affiliation: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, and Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa Bill and Melinda Gates Foundation, Seattle, Washington, USA.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Hanekom
authors.affiliation: Aeras, Rockville, Maryland, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Evans
authors.affiliation: Aurum Institute, Johannesburg, South Africa School of Public Health, University of Witwatersrand, Johannesburg, South Africa.
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Churchyard
authors.affiliation: HIV Vaccine Trials Network, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA Department of Medicine, Department of Global Health, University of Washington School of Medicine, Seattle, Washington, USA.
authors.forename: James G
authors.initials: JG
authors.lastname: Kublin
authors.affiliation: Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Linda-Gail
authors.initials: LG
authors.lastname: Bekker
authors.affiliation: Statistical Center for HIV Research, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Self
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D060085:Coinfection; D015658:HIV Infections / Q000150:complications; D006801:Humans; D023421:Models, Animal; D008962:Models, Theoretical; D009163:Mycobacterium bovis; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000502:physiology; D014376:Tuberculosis / Q000150:complications / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines; D014611:Vaccination
chemical_list: D032581:Tuberculosis Vaccines