The roles of latency-associated antigens in tuberculosis vaccines

Avarvand, Arshid Yousefi; Khademi, Farzad; Tafaghodi, Mohsen; Zahra, Ahmadipour; Moradi, Bagher; Meshkat, Zahra

doi:10.1016/j.ijtb.2019.04.012

Cited by 7 publications

(4 citation statements)

References 37 publications

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“…Tuberculosis (TB) is a contagious disease with approximately 1.7 billion latently infected people and over 1.2 million deaths annually. TB is among the 10 causes of death worldwide, according to the latest World Health Organization (WHO) report which can be controlled using early vaccination as well as rapid detection and treatment with the first-and second anti-TB drugs (1)(2)(3)(4). However, the emergence of Mycobacterium tuberculosis (M. tuberculosis ) resistant strains particularly rifampicin-resistant and multidrug-resistant TB (MDR) have led to treatment failures (5).…”

Section: Introductionmentioning

confidence: 99%

Enhancement of the immunogenicity of a Mycobacterium tuberculosis fusion protein using ISCOMATRIX and PLUSCOM nano-adjuvants after nasal administration in mice

Avarvand,

Meshkat,

Khademi

et al. 2024

Preprint

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Background: Tuberculosis (TB), a contagious disease caused by Mycobacterium tuberculosis (M. tuberculosis), remains a health problem worldwide and this infection has the highest mortality rate among bacterial infections. Current studies suggest that intranasal administration of new tuberculosis vaccines could enhance the immunogenicity of M. tuberculosis antigens. Hence, we aim to evaluate the protective efficacy and immunogenicity of HspX/EsxS fusion protein of M. tuberculosis along with ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA through the intranasal administration in mice model. Methods: in present study, the recombinant fusion protein was expressed in Escherichia coli and purified and used to prepare different nanoparticle formulations in combination with ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA. Mice were intranasally vaccinated with each formulation three times at an interval of 2 weeks. Three weeks after final vaccination, IFN-γ, IL-4. IL-17 and TGF-β concentration in supernatant of cultured splenocytes of vaccinated mice as well as serum titers of IgG1 and IgG2a and sIgA titers in nasal lavagewere determined. Results: According to obtained results, intranasally vaccinated mice with formulations containing ISCOMATRIX and PLUSCOM nano-adjuvants and MPLA could effectively induced IFN-γ and sIgA responses. Moreover, both HspX/EsxS/ISCOMATRIX/MPLA and HspX/EsxS/PLUSCOM/MPLA and their BCG booster formulation could strongly stimulate the immune system and enhance the immunogenicity of M. tuberculosis antigens. Conclusion: The results demonstrate the potential of HspX/EsxS-fused protein in combination with ISCOMATRIX, PLUSCOM and MPLA after nasal administration in enhancing immune response against of M. tuberculosis antigens. Both nanoparticles were good adjuvants in order to promote immunogenicity of TB fused antigen. so, nasal immunization with these formulations, could induce immune responses and considered as new TB vaccine or as BCG booster.

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Section: Introductionmentioning

confidence: 99%

Enhancement of the immunogenicity of a Mycobacterium tuberculosis fusion protein using ISCOMATRIX and PLUSCOM nano-adjuvants after nasal administration in mice

Avarvand,

Meshkat,

Khademi

et al. 2024

Preprint

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“…Indeed, it is increasingly recognized that next-generation vaccine strategies need to consider the life cycle of M.tb bacilli during infection 6,13,17 . Upon infection, confronting the host's immune pressure and environmental stresses such as nutrient deprivation and oxygen depletion [18][19][20] , M.tb bacilli metabolically shift from an actively replicating state to a quiescent state of persistence, becoming non-replicating persisters or dormant M.tb bacilli, a feature of latent TB.…”

Section: Introductionmentioning

confidence: 99%

“…This process is associated with differential M.tb antigen (Ag) expression with some Ags such as Ag85 complex proteins (AgA/B/C) predominantly produced during the acute stage of infection, some including ESX secretion system proteins (TB10.4, ESAT6 etc.) produced throughout the course of infection, and some expressed during either the latency/dormancy or resusciation 6,13,17,21,22 . Infection stage-dependent Ag expression represents one of the immune-evasive strategies for M.tb and can render the current vaccines expressing only acute-stage Ags ineffective, particularly in host defense against chronic and latent TB 23 .…”

Section: Introductionmentioning

confidence: 99%

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Intranasal multivalent adenoviral-vectored vaccine protects against replicating and dormant M.tb in conventional and humanized mice

et al. 2023

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Viral-vectored vaccines are highly amenable for respiratory mucosal delivery as a means of inducing much-needed mucosal immunity at the point of pathogen entry. Unfortunately, current monovalent viral-vectored tuberculosis (TB) vaccine candidates have failed to demonstrate satisfactory clinical protective efficacy. As such, there is a need to develop next-generation viral-vectored TB vaccine strategies which incorporate both vaccine antigen design and delivery route. In this study, we have developed a trivalent chimpanzee adenoviral-vectored vaccine to provide protective immunity against pulmonary TB through targeting antigens linked to the three different growth phases (acute/chronic/dormancy) of Mycobacterium tuberculosis (M.tb) by expressing an acute replication-associated antigen, Ag85A, a chronically expressed virulence-associated antigen, TB10.4, and a dormancy/resuscitation-associated antigen, RpfB. Single-dose respiratory mucosal immunization with our trivalent vaccine induced robust, sustained tissue-resident multifunctional CD4+ and CD8+ T-cell responses within the lung tissues and airways, which were further quantitatively and qualitatively improved following boosting of subcutaneously BCG-primed hosts. Prophylactic and therapeutic immunization with this multivalent trivalent vaccine in conventional BALB/c mice provided significant protection against not only actively replicating M.tb bacilli but also dormant, non-replicating persisters. Importantly, when used as a booster, it also provided marked protection in the highly susceptible C3HeB/FeJ mice, and a single respiratory mucosal inoculation was capable of significant protection in a humanized mouse model. Our findings indicate the great potential of this next-generation TB vaccine strategy and support its further clinical development for both prophylactic and therapeutic applications.

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Tuberculosis

Bonville

Domachowske

2020

Vaccines

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The roles of latency-associated antigens in tuberculosis vaccines

Cited by 7 publications

References 37 publications

Enhancement of the immunogenicity of a Mycobacterium tuberculosis fusion protein using ISCOMATRIX and PLUSCOM nano-adjuvants after nasal administration in mice

Enhancement of the immunogenicity of a Mycobacterium tuberculosis fusion protein using ISCOMATRIX and PLUSCOM nano-adjuvants after nasal administration in mice

Intranasal multivalent adenoviral-vectored vaccine protects against replicating and dormant M.tb in conventional and humanized mice

Tuberculosis

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