Novel Vaccination Strategies Against Tuberculosis

Andersen, Peter; Kaufmann, Stefan H. E.

doi:10.1002/9783527611614.ch31

Cited by 4 publications

(4 citation statements)

References 111 publications

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“…Tuberculosis (TB) is a major cause of death worldwide. Despite the extensive research, no effective vaccine against adult pulmonary TB has been developed (Andersen & Kaufmann, 2014). Therefore, longterm antibiotic treatment remains the standard of care (Zumla et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…It is long known that T cells play a major role in TB immunity and are the target of current vaccination strategies (Cooper, 2009;Andersen & Kaufmann, 2014). However, more recent evidence points toward a role of B cells in modulating immune responses to MTB infection, for example, as antigen-presenting cells or through the production of cytokines and antibodies (Glatman-Freedman & ways: by the direct blocking of host cell invasion and neutralization of bacterial products, or indirectly through Fc-mediated complement and cell activation mechanisms through Fc receptors (Ravetch & Clynes, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Human isotype‐dependent inhibitory antibody responses against Mycobacterium tuberculosis

et al. 2016

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Accumulating evidence from experimental animal models suggests that antibodies play a protective role against tuberculosis (TB). However, little is known about the antibodies generated upon Mycobacterium tuberculosis (MTB) exposure in humans. Here, we performed a molecular and functional characterization of the human B‐cell response to MTB by generating recombinant monoclonal antibodies from single isolated B cells of untreated adult patients with acute pulmonary TB and from MTB‐exposed healthcare workers. The data suggest that the acute plasmablast response to MTB originates from reactivated memory B cells and indicates a mucosal origin. Through functional analyses, we identified MTB inhibitory antibodies against mycobacterial antigens including virulence factors that play important roles in host cell infection. The inhibitory activity of anti‐MTB antibodies was directly linked to their isotype. Monoclonal as well as purified serum IgA antibodies showed MTB blocking activity independently of Fc alpha receptor expression, whereas IgG antibodies promoted the host cell infection. Together, the data provide molecular insights into the human antibody response to MTB and may thereby facilitate the design of protective vaccination strategies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Human isotype‐dependent inhibitory antibody responses against Mycobacterium tuberculosis

et al. 2016

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“…Subunit vaccines have emerged as a prominent research area for novel tuberculosis vaccines owing to their inherent advantages of safety, stringent standards, cost-effectiveness, and ease of transportation (8)(9)(10). In recent years, substantial progress has been made in TB subunit vaccines, with several vaccines in clinical trials, such as MVA85A, M72/AS01, and H51:IC31 (1).…”

Section: Introductionmentioning

confidence: 99%

A novel multistage antigens ERA005f confer protection against Mycobacterium tuberculosis by driving Th-1 and Th-17 type T cell immune responses

Fan,

Zhao,

Wang

et al. 2023

Front. Immunol.

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IntroductionTuberculosis (TB) is a major threat to human health. In 2021, TB was the second leading cause of death after COVID-19 among infectious diseases. The Bacillus Calmette–Guérin vaccine (BCG), the only licensed TB vaccine, is ineffective against adult TB. Therefore, there is an urgent need to develop new effective vaccines.MethodsIn this study, we developed a novel multistage subunit vaccine (ERA005f) comprising various proteins expressed in metabolic states, based on three immunodominant antigens (ESAT-6, Rv2628, and Ag85B). We utilized the E. coli prokaryotic expression system to express ERA005f and subsequently purified the protein using nickel affinity chromatography and anion exchange. Immunogenicity and protective efficacy of ERA005f and ERA005m were evaluated in BALB/c mice.ResultsERA005f was consistently expressed as an inclusion body in a prokaryotic expression system, and a highly pure form of the protein was successfully obtained. Both ERA005f and ERA005m significantly improved IgG titers in the serum. In addition, mice immunized with ERA005f and ERA005m generated higher titers of antigen-specific IgG2a than the other groups. Elispot results showed that, compared with other groups, ERA005f increased the numbers of IFN-γ-secreting and IL-4-secreting T cells, especially the number of IFN-γ-secreting T cells. Meanwhile, ERA005f induced a higher number of IFN-γ+ T lymphocytes than ERA005m did. In addition, ERA005f improved the expression of cytokines, including IFN-γ, IL-12p70, TNF-α, IL-17, and GM-CSF and so on. Importantly, both ERA005f and ERA005m significantly inhibited the growth of Mtb.ConclusionThe novel multistage antigen ERA005f elicited a strong antigen-specific humoral response and Th-1 and Th-17 cell-mediated immunity in mice. Meanwhile, it can effectively inhibit H37Rv growth in vitro, and represents a correlate of protection in vivo, indicating that ERA005f may exhibit excellent protective efficacy against Mycobacterium tuberculosis H37Rv infection. Our study suggests that ERA005f has the potential to be a promising multistage tuberculosis vaccine candidate.

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“…Attenuated between 1906 and 1921 by Calmette and Guérin, it has since then been used as a vaccine against TB. M. bovis bacille Calmette-Guérin (BCG) is currently the only licensed vaccine against TB (Andersen and Kaufmann, 2014). Although BCG has marginal effect against pulmonary TB, it protects against extrapulmonary disease forms in infants (WHO, 2015).…”

Section: Introductionmentioning

confidence: 99%

Syndecans promote mycobacterial internalization by lung epithelial cells

Zimmermann

Saiga

Houthuys

et al. 2016

Cellular Microbiology

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Pulmonary tuberculosis (TB) is an airborne disease caused by the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb). Alveolar epithelial cells and macrophages are the first point of contact for Mtb in the respiratory tract. However, the mechanisms of mycobacterial attachment to, and internalization by, nonprofessional phagocytes, such as epithelial cells, remain incompletely understood. We identified syndecan 4 (Sdc4) as mycobacterial attachment receptor on alveolar epithelial cells. Sdc4 mRNA expression was increased in human and mouse alveolar epithelial cells after mycobacterial infection. Sdc4 knockdown in alveolar epithelial cells or blocking with anti-Sdc4 antibody reduced mycobacterial attachment and internalization. At the molecular level, interactions between epithelial cells and mycobacteria involved host Sdc and the mycobacterial heparin-binding hemagglutinin adhesin. In vivo, Sdc1/Sdc4 double-knockout mice were more resistant to Mtb colonization of the lung. Our work reveals a role for distinct Sdcs in promoting mycobacterial entry into alveolar epithelial cells with impact on outcome of TB disease.

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Novel Vaccination Strategies Against Tuberculosis

Cited by 4 publications

References 111 publications

Human isotype‐dependent inhibitory antibody responses against Mycobacterium tuberculosis

Human isotype‐dependent inhibitory antibody responses against Mycobacterium tuberculosis

A novel multistage antigens ERA005f confer protection against Mycobacterium tuberculosis by driving Th-1 and Th-17 type T cell immune responses

Syndecans promote mycobacterial internalization by lung epithelial cells

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