Impact of Structural Domains of the Heparin Binding Hemagglutinin of Mycobacterium tuberculosis on Function

Delogu, Giovanni; Fadda, Giovanni; Brennan, Michael J.

doi:10.2174/092986612802762697

Cited by 10 publications

(7 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the Lp _HBD construct, the HBD fragment from the HBHA surface protein of M. tuberculosis was fused to the C-terminal end of the AgE6 antigen (Figure 1B) replacing the DC-targeting peptide. HBD is a methylated lysine-rich C-terminal fragment of HBHA that mediates an interaction with epithelial and non-phagocytic cells (45–47).…”

Section: Resultsmentioning

confidence: 99%

Inactivated Lactobacillus plantarum Carrying a Surface-Displayed Ag85B-ESAT-6 Fusion Antigen as a Booster Vaccine Against Mycobacterium tuberculosis Infection

et al. 2019

View full text Add to dashboard Cite

Vaccination is considered the most effective strategy for controlling tuberculosis (TB). The existing vaccine, the Bacille Calmette-Guérin (BCG), although partially protective, has a number of limitations. Therefore, there is a need for developing new TB vaccines and several strategies are currently exploited including the use of viral and bacterial delivery vectors. We have previously shown that Lactobacillus plantarum ( Lp ) producing Ag85B and ESAT-6 antigens fused to a dendritic cell-targeting peptide (referred to as Lp _DC) induced specific immune responses in mice. Here, we analyzed the ability of two Lp -based vaccines, Lp _DC and Lp _HBD (in which the DC-binding peptide was replaced by an HBD-domain directing the antigen to non-phagocytic cells) to activate antigen-presenting cells, induce specific immunity and protect mice from Mycobacterium tuberculosis infection. We tested two strategies: (i) Lp as BCG boosting vaccine (a heterologous regimen comprising parenteral BCG immunization followed by intranasal Lp boost), and (ii) Lp as primary vaccine (a homologous regimen including subcutaneous priming followed by intranasal boost). The results showed that both Lp constructs applied as a BCG boost induced specific cellular immunity, manifested in T cell proliferation, antigen-specific IFN-γ responses and multifunctional T cells phenotypes. More importantly, intranasal boost with Lp _DC or Lp _HBD enhanced protection offered by BCG, as shown by reduced M. tuberculosis counts in lungs. These findings suggest that Lp constructs could be developed as a potential mucosal vaccine platform against mycobacterial infections.

show abstract

Section: Resultsmentioning

confidence: 99%

Inactivated Lactobacillus plantarum Carrying a Surface-Displayed Ag85B-ESAT-6 Fusion Antigen as a Booster Vaccine Against Mycobacterium tuberculosis Infection

et al. 2019

View full text Add to dashboard Cite

show abstract

“…BCG vaccination independency, offered by the commercialized IGRAs but not the TST, is also an essential feature for an LTBI screening test. nHBHA is produced by all members of the M. tuberculosis complex, including the attenuated BCG strain of M. bovis (19). However, BCG vaccination in infancy did not appear to influence test results in adults when investigated in the 96-h nHBHA-IGRA reference study (5).…”

Section: Discussionmentioning

confidence: 97%

Key Role of Effector Memory CD4⁺T Lymphocytes in a Short-Incubation Heparin-Binding Hemagglutinin Gamma Interferon Release Assay for the Detection of Latent Tuberculosis

Wyndham-Thomas¹,

Corbière²,

Dirix³

et al. 2014

Clin. Vaccine Immunol.

View full text Add to dashboard Cite

The treatment of latent tuberculosis infection (LTBI) in target populations is one of the current WHO strategies for preventing active tuberculosis (TB) infection and reducing theT he screening and treatment for LTBI in target populations in order to prevent TB and reduce the Mycobacterium tuberculosis reservoir are some of the main strategies of the WHO's Global Plan to Stop TB (http://www.who.int/tb/publications/global _report/en). However, a major obstacle to the instauration and effectiveness of these preventive measures resides in the lack of a gold standard LTBI screening tool.For several decades, the tuberculin skin test (TST) has been the main screening test for LTBI despite its lack of both sensitivity and specificity (1). Subsequently, T-cell-based gamma interferon release assays (IGRAs) in response to antigens encoded in the M. tuberculosis genomic region of difference 1 (RD-1) and RD-11 were developed and commercialized (QuantiFERON-TB Gold In-Tube [QFT-GIT] and T-SPOT.TB tests), with the objective of offering a more powerful diagnostic tool for LTBI. These tests offer a higher specificity than TST particularly in countries with high Mycobacterium bovis BCG vaccination coverage (2). However, recent studies suggest that these short-incubation RD-1-based IGRAs may have suboptimal sensitivities (3, 4).An alternative IGRA in response to the native mycobacterial antigen heparin-binding hemagglutinin (nHBHA-IGRA) that uses a longer incubation time than the commercialized IGRA has been validated in immunocompetent adults in the screening for LTBI (5). This assay not only demonstrates a high sensitivity and specificity for LTBI diagnosis but also a capacity to detect remote M. tuberculosis infections, a substantial advantage over the commercialized IGRAs (5-7).Remote M. tuberculosis infections are generally believed to be identified through central memory T-cell (Tcm) responses detected with long-incubation IGRAs (3, 4). Here, however, we demonstrate that both recent and remote M. tuberculosis infections can be identified through effector memory T-cell (Tem) responses using a short-incubation nHBHA-IGRA, the upgraded assay presented in this study. Our results suggest that the detection of IFN-␥-producing CD4 ϩ Tem in response to nHBHA reflects the persistence of M. tuberculosis antigens and therefore a true state of latency.(These results were presented in part at the European Congress of Immunology, Glasgow, Scotland, 5 to 8 September 2012, and at the MycoClub,

show abstract

“…HBHA mediates adhesion of the bacilli to epithelial cells but not macrophages and is involved in the dissemination of M. tuberculosis from the site of primary infection [44,45]. The molecular characterization of HBHA sheds light on the structure-function relationship and their impact on the mechanism of pathogenesis [46][47][48][49], and the information gathered could open new avenues for the development of innovative prophylactic and therapeutic strategies against TB.…”

Section: Hbhamentioning

confidence: 99%

Exploiting the mycobacterial cell wall to design improved vaccines against tuberculosis

Morandi

Sali

Manganelli

et al. 2013

J Infect Dev Ctries

Self Cite

View full text Add to dashboard Cite

The only vaccine available against tuberculosis (TB), the Bacille Calmette-Guerin (BCG), does not provide effective protection against the most common forms of adult TB and in recent years efforts have been made to develop a new and improved vaccine. Among the strategies implemented, the generation of a new live attenuated mycobacterial strain is seen as one of the most promising and feasible, for scientific, ethical and practical reasons. The new understanding of the biology of the tubercle bacilli and of host-pathogen interaction processes, coupled with the possibility to engineer BCG or M. tuberculosis, opened new avenues to design "intelligent" vaccines, capable of eliciting the immune response associated with protection while avoiding the induction of the host immune response associated with immunopathology. The complex and highly immunogenic mycobacterial cell wall can shape the general and antigen specific immune response elicited following immunization, and the possibility to exploit this knowledge may lead to the development of new vaccines that could help conquer this ancient human disease.

show abstract

Impact of Structural Domains of the Heparin Binding Hemagglutinin of Mycobacterium tuberculosis on Function

Cited by 10 publications

References 40 publications

Inactivated Lactobacillus plantarum Carrying a Surface-Displayed Ag85B-ESAT-6 Fusion Antigen as a Booster Vaccine Against Mycobacterium tuberculosis Infection

Inactivated Lactobacillus plantarum Carrying a Surface-Displayed Ag85B-ESAT-6 Fusion Antigen as a Booster Vaccine Against Mycobacterium tuberculosis Infection

Key Role of Effector Memory CD4⁺T Lymphocytes in a Short-Incubation Heparin-Binding Hemagglutinin Gamma Interferon Release Assay for the Detection of Latent Tuberculosis

Exploiting the mycobacterial cell wall to design improved vaccines against tuberculosis

Contact Info

Product

Resources

About

Impact of Structural Domains of the Heparin Binding Hemagglutinin of Mycobacterium tuberculosis on Function

Cited by 10 publications

References 40 publications

Inactivated Lactobacillus plantarum Carrying a Surface-Displayed Ag85B-ESAT-6 Fusion Antigen as a Booster Vaccine Against Mycobacterium tuberculosis Infection

Inactivated Lactobacillus plantarum Carrying a Surface-Displayed Ag85B-ESAT-6 Fusion Antigen as a Booster Vaccine Against Mycobacterium tuberculosis Infection

Key Role of Effector Memory CD4+T Lymphocytes in a Short-Incubation Heparin-Binding Hemagglutinin Gamma Interferon Release Assay for the Detection of Latent Tuberculosis

Exploiting the mycobacterial cell wall to design improved vaccines against tuberculosis

Contact Info

Product

Resources

About

Key Role of Effector Memory CD4⁺T Lymphocytes in a Short-Incubation Heparin-Binding Hemagglutinin Gamma Interferon Release Assay for the Detection of Latent Tuberculosis