Tuberculosis Vaccine Types and Timings

Orme, Ian M.

doi:10.1128/cvi.00718-14

Cited by 39 publications

(32 citation statements)

References 89 publications

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“…These strains have not been observed in humans for 70 years or more and, thus, may not be relevant to the M. tuberculosis strains circulating today. Use of clinically relevant M. tuberculosis isolates for preclinical vaccine efficacy and basic research has been recommended (44). M. tuberculosis HN878 is a recent clinical isolate of the Beijing lineage.…”

Section: Et Al Have Shown a Transient Increase In Ifn-␥ From Cd4mentioning

confidence: 99%

Protection and Long-Lived Immunity Induced by the ID93/GLA-SE Vaccine Candidate against a Clinical Mycobacterium tuberculosis Isolate

Baldwin

Reese

Huang

et al. 2016

Clin Vaccine Immunol

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dMycobacterium tuberculosis HN878 represents a virulent clinical strain from the W-Beijing family, which has been tested in small animal models in order to study its virulence and its induction of host immune responses following infection. This isolate causes death and extensive lung pathology in infected C57BL/6 mice, whereas lab-adapted strains, such as M. tuberculosis H37Rv, do not. The use of this clinically relevant isolate of M. tuberculosis increases the possibilities of assessing the long-lived efficacy of tuberculosis vaccines in a relatively inexpensive small animal model. This model will also allow for the use of knockout mouse strains to critically examine key immunological factors responsible for long-lived, vaccine-induced immunity in addition to vaccine-mediated prevention of pulmonary immunopathology. In this study, we show that the ID93/glucopyranosyl lipid adjuvant (GLA)-stable emulsion (SE) tuberculosis vaccine candidate, currently in human clinical trials, is able to elicit protection against M. tuberculosis HN878 by reducing the bacterial burden in the lung and spleen and by preventing the extensive lung pathology induced by this pathogen in C57BL/6 mice.T he development of an effective Mycobacterium tuberculosis vaccine, and increased availability of novel drugs targeting drug-resistant strains, would significantly contribute to decreasing the continuing spread of this global disease. Nine million people were estimated to have contracted tuberculosis (TB) in 2013, with 1.5 million deaths occurring annually (1). Overall, 3.5% of new cases and 20.5% of previously treated cases are multidrugresistant (MDR) TB (1), although this can be as high as 35% and 75%, respectively, in central Asian countries. The Beijing lineage of TB has been associated with a number of MDR TB outbreaks (2-6) and accounts for approximately 13% of isolates worldwide (7). The Beijing lineage itself has expanded more rapidly than other lineages (8); this may be due to the higher virulence of modern strains compared with phylogenetically older sublineages (9-11). The clinical isolate, HN878, is a representative strain from the W-Beijing lineage. The HN878 isolate has been studied in mice to characterize the infectivity and pathogenicity of this virulent clinical strain of M. tuberculosis (12)(13)(14). These same studies have provided insight into the role of the immune response generated to this pathogen in animals and humans and how the immune response to HN878 contributes to the pathology induced following infection with this isolate. Mice infected with the hypervirulent HN878 strain have increased type I interferon (IFN) expression in the lung and decreased Th1 immunity (12), and HN878 infection in IFN-␣/␤R-deficient mice results in decreased bacterial growth (13). In humans, a type I IFN-␣ molecular signature, expressed by a population of isolated neutrophils, was observed in patients with active TB (15). More recently, analysis using a whole-genome microarray approach showed a similar type I interferon molecular signa...

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Section: Et Al Have Shown a Transient Increase In Ifn-␥ From Cd4mentioning

confidence: 99%

Protection and Long-Lived Immunity Induced by the ID93/GLA-SE Vaccine Candidate against a Clinical Mycobacterium tuberculosis Isolate

Baldwin

Reese

Huang

et al. 2016

Clin Vaccine Immunol

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“…The increase in multidrug-resistance incidence3, the association with HIV-infection and non-communicable diseases4, the lack of an efficient vaccine and the difficulty in timely diagnosing TB5 represent just a few of the challenges that need to be addressed. Improved diagnostics6, safer and more accessible treatments for active and latent Mycobacterium tuberculosis (Mtb ) infection7 and new effective pre- and post-exposure vaccines must all be developed before we can reach TB elimination89.…”

mentioning

confidence: 99%

“…We have proposed to define the Mtb antigen repertoire expressed in vivo during pulmonary infection. The lung is the primary organ in which Mtb resides and interacts with the human immune system9112122, and where it initiates the process of infection and pathogenesis, setting the stage for future transmission.…”

mentioning

confidence: 99%

New Genome-Wide Algorithm Identifies Novel In-Vivo Expressed Mycobacterium Tuberculosis Antigens Inducing Human T-Cell Responses with Classical and Unconventional Cytokine Profiles

Coppola

Meijgaarden

Franken

et al. 2016

Sci Rep

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New strategies are needed to develop better tools to control TB, including identification of novel antigens for vaccination. Such Mtb antigens must be expressed during Mtb infection in the major target organ, the lung, and must be capable of eliciting human immune responses. Using genome-wide transcriptomics of Mtb infected lungs we developed data sets and methods to identify IVE-TB (in-vivo expressed Mtb) antigens expressed in the lung. Quantitative expression analysis of 2,068 Mtb genes from the predicted first operons identified the most upregulated IVE-TB genes during in-vivo pulmonary infection. By further analysing high-level conservation among whole-genome sequenced Mtb-complex strains (n = 219) and algorithms predicting HLA-class-Ia and II presented epitopes, we selected the most promising IVE-TB candidate antigens. Several of these were recognized by T-cells from in-vitro Mtb-PPD and ESAT6/CFP10-positive donors by proliferation and multi-cytokine production. This was validated in an independent cohort of latently Mtb-infected individuals. Significant T-cell responses were observed in the absence of IFN-γ-production. Collectively, the results underscore the power of our novel antigen discovery approach in identifying Mtb antigens, including those that induce unconventional T-cell responses, which may provide important novel tools for TB vaccination and biomarker profiling. Our generic approach is applicable to other infectious diseases.

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“…These include constructing recombinant BCG strains overexpressing M. tuberculosis antigens or lysins to allow BCG to escape phagocytic endosomes (36). Once in the cytoplasm, induction of apoptosis is followed by cross-presentation of mycobacterial antigens, allowing more-efficient priming of T cells.…”

Section: Discussionmentioning

confidence: 99%

Induction of Unconventional T Cells by a Mutant Mycobacterium bovis BCG Strain Formulated in Cationic Liposomes Correlates with Protection against Mycobacterium tuberculosis Infections of Immunocompromised Mice

Derrick

Yabe

Morris

et al. 2016

Clin Vaccine Immunol

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Despite the widespread use of Mycobacterium bovis BCG vaccine and the availability of effective chemotherapy, tuberculosis (TB) remains an immense global public health challenge, with approximately 9 million new cases and 1.4 million deaths per year. Overall, an estimated 2 billion people are infected with M. tuberculosis worldwide (1, 2). These alarming statistics have made it obvious that current interventions are not controlling the epidemic. The reasons for the current TB problem are multifaceted and include the lack of an efficacious vaccine and the emergence of multidrug-resistant and extremely drug-resistant M. tuberculosis strains (1, 3). Importantly, the convergence of the HIV and TB epidemics has, without question, intensified the TB problem. Since HIV-infected individuals are considerably more susceptible to pathogens due to their immunocompromised state, coinfected individuals are 30 times more likely to develop active TB than those infected with M. tuberculosis only. In fact, TB causes 25% of all HIV-related deaths worldwide (2).While BCG is one of the most widely used global vaccines, its impact on the current TB epidemic has clearly been inadequate. Randomized controlled clinical trials and retrospective case-control studies have shown that BCG immunization is effective in reducing cases of severe disseminated TB in children; however, the effectiveness of BCG in preventing pulmonary TB has been highly variable, ranging from 0% to 80% (4). Furthermore, protection is often not highly persistent, with substantial waning of BCG-induced protective responses generally seen during the first decade after immunization (5). Given the suboptimal efficacy in the context of the devastating TB epidemic, there is an urgent global health need to develop a new TB immunization strategy. Consequently, many TB researchers are developing strategies to amplify BCG-induced antituberculosis protective responses. A popular approach involves boosting with protein-or virus-vectored vaccines after a priming BCG immunization. Alternatively, a potentially simpler and less expensive strategy involves formulating BCG in a liposome-forming adjuvant. Lipid encapsulation of BCG has been shown to improve the immunogenicity and protective efficacy of BCG immunization in mice, guinea pigs, badgers, and cattle (6-10).Our group recently demonstrated that formulation of a BCG⌬mmaA4 (BCG-A4) mutant in DDA/TDB adjuvant (A4/ Adj) increased the level and persistence of BCG-induced immune responses relative to those produced by conventional BCG and

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Tuberculosis Vaccine Types and Timings

Cited by 39 publications

References 89 publications

Protection and Long-Lived Immunity Induced by the ID93/GLA-SE Vaccine Candidate against a Clinical Mycobacterium tuberculosis Isolate

Protection and Long-Lived Immunity Induced by the ID93/GLA-SE Vaccine Candidate against a Clinical Mycobacterium tuberculosis Isolate

New Genome-Wide Algorithm Identifies Novel In-Vivo Expressed Mycobacterium Tuberculosis Antigens Inducing Human T-Cell Responses with Classical and Unconventional Cytokine Profiles

Induction of Unconventional T Cells by a Mutant Mycobacterium bovis BCG Strain Formulated in Cationic Liposomes Correlates with Protection against Mycobacterium tuberculosis Infections of Immunocompromised Mice

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