Quest for correlates of protection against tuberculosis.
نویسندگان
چکیده
A major impediment to tuberculosis (TB) vaccine development is the lack of reliable correlates of immune protection or biomarkers that would predict vaccine efficacy. Gamma interferon (IFN-γ) produced by CD4(+) T cells and, recently, multifunctional CD4(+) T cells secreting IFN-γ, tumor necrosis factor (TNF), and interleukin-2 (IL-2) have been used in vaccine studies as a measurable immune parameter, reflecting activity of a vaccine and potentially predicting protection. However, accumulating experimental evidence suggests that host resistance against Mycobacterium tuberculosis infection is independent of IFN-γ and TNF secretion from CD4(+) T cells. Furthermore, the booster vaccine MVA85A, despite generating a high level of multifunctional CD4(+) T cell response in the host, failed to confer enhanced protection in vaccinated subjects. These findings suggest the need for identifying reliable correlates of protection to determine the efficacy of TB vaccine candidates. This article focuses on alternative pathways that mediate M. tuberculosis control and their potential for serving as markers of protection. The review also discusses the significance of investigating the natural human immune response to M. tuberculosis to identify the correlates of protection in vaccination.
منابع مشابه
The quest for a new vaccine against tuberculosis.
Tuberculosis (TB) is still one of the deadliest human diseases, killing 1,6 million people each year, mostly in developing countries. The vaccine currently used, Bacille Calmette and Guerin (BCG), is effective in preventing the most severe disseminated forms of disease in children and newborns, but its efficacy against active TB in adults has been challenged by several clinical studies. It is a...
متن کاملGranuloma correlates of protection against tuberculosis and mechanisms of immune modulation by Mycobacterium tuberculosis.
BACKGROUND The BCG vaccine is ineffective against adult tuberculosis. Hence, new antituberculosis vaccines are needed. Correlates of protection against tuberculosis are not known. We studied the effects of BCG vaccination on gene expression in tuberculosis granulomas using macaques. METHODS Macaques were BCG-vaccinated or sham-vaccinated and then challenged with virulent Mycobacterium tubercu...
متن کاملA novel formulation of Mtb72F DNA vaccine for immunization against tuberculosis
Objective(s): Mycobacterium tuberculosis (M. tuberculosis), an intracellular pathogen, causes 1.5 million deaths globally. Bacilli Calmette-Guérin (BCG) is commonly administered to protect people against M. tuberculosis infection; however, there are some obstacles with this first-generation vaccine. DNA vaccines, the third generation vaccines, can induce cellular immun...
متن کاملHigh frequency of CD4+ T cells specific for the TB10.4 protein correlates with protection against Mycobacterium tuberculosis infection.
TB10.4 is a newly identified antigen of Mycobacterium tuberculosis recognized by human and murine T cells upon mycobacterial infection. Here, we show that immunization with Mycobacterium bovis BCG induces a strong, genetically controlled, Th1 immune response against TB10.4 in mice. BALB/c and C57BL/6 strains behave as high and low responders to TB10.4 protein, respectively. The TB10.4:74-88 pep...
متن کاملMannose-binding lectin polymorphisms in clinical tuberculosis.
Mannose-binding lectin (MBL) mediates protection against infections by using the complement system, but certain microorganisms may increase infectivity by exploiting this host defense system. Thus, it has been speculated whether genetically determined low MBL levels may confer partial protection against certain intracellular microorganisms, such as Mycobacterium tuberculosis. We investigated MB...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Clinical and vaccine immunology : CVI
دوره 22 3 شماره
صفحات -
تاریخ انتشار 2015