HspX protein as a candidate vaccine against Mycobacterium tuberculosis: an overview

Yousefi-Avarvand, Arshid; Tafaghodi, Mohsen; Soleimanpour, Saman; Khademi, Farzad

doi:10.1007/s11515-018-1494-2

Cited by 13 publications

(10 citation statements)

References 26 publications

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“…Most anti-tuberculosis vaccines that are currently ongoing clinical trials target the early expressed antigens. However, latency-associated antigens, such as HspX, have recently emerged in the development of anti-tuberculosis vaccines [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs

et al. 2021

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New strategies providing protection against tuberculosis (TB) are still pending. The airborne nature of Mycobacterium tuberculosis (M.tb) infection assumes that the mucosal delivery of the TB vaccine could be a more promising strategy than the systemic route of immunization. We developed a mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing truncated NS1 protein NS1(1–124) and a full-length TB10.4 and HspX proteins of M.tb within an NS1 protein open reading frame. The Flu/THSP vector was safe and stimulated a systemic TB-specific CD4+ and CD8+ T-cell immune response after intranasal immunization in mice. Double intranasal immunization with the Flu/THSP vector induced protection against two virulent M.tb strains equal to the effect of BCG subcutaneous injection in mice. In a guinea pig TB model, one intranasal immunization with Flu/THSP improved protection against M.tb when tested as a vaccine candidate for boosting BCG-primed immunity. Importantly, enhanced protection provided by a heterologous BCG-prime → Flu/THSP vector boost immunization scheme was associated with a significantly reduced lung and spleen bacterial burden (mean decrease of 0.77 lg CFU and 0.72 lg CFU, respectively) and improved lung pathology 8.5 weeks post-infection with virulent M.tb strain H37Rv.

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Section: Discussionmentioning

confidence: 99%

Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs

et al. 2021

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“…It can induce strong cellular and humoral immune responses in latent phase of tuberculosis infection [13][14][15][16]. The perspectives of the use of HspX protein as a candidate vaccine against Mycobacterium tuberculosis are discussed in the review by Yousefi-Avarvand et al [17]. It should be also noted that both TB10.4 and HspX are encoded by Bacillus Calmette-Guerin which makes them useful in a prime-boost immunization scheme [18].…”

Section: Introductionmentioning

confidence: 99%

Enhancement of the Local CD8+ T-Cellular Immune Response to Mycobacterium tuberculosis in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens

et al. 2021

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BCG is the only licensed vaccine against Mycobacterium tuberculosis (M.tb) infection. Due to its intramuscular administration route, BCG is unable to induce a local protective immune response in the respiratory system. Moreover, BCG has a diminished ability to induce long-lived memory T-cells which are indispensable for antituberculosis protection. Recently we described the protective efficacy of new mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing TB10.4 and HspX proteins of M.tb within an NS1 influenza protein open reading frame. In the present work, the innate and adaptive immune response to immunization with the Flu/THSP and the immunological properties of vaccine candidate in the BCG-prime → Flu/THSP vector boost vaccination scheme are studied in mice. It was shown that the mucosal administration of Flu/THSP induces the incoming of interstitial macrophages in the lung tissue and stimulates the expression of co-stimulatory CD86 and CD83 molecules on antigen-presenting cells. The T-cellular immune response to Flu/THSP vector was mediated predominantly by the IFNγ-producing CD8+ lymphocytes. BCG-prime → Flu/THSP vector boost immunization scheme was shown to protect mice from severe lung injury caused by M.tb infection due to the enhanced T-cellular immune response, mediated by antigen-specific effector and central memory CD4+ and CD8+ T-lymphocytes.

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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%

“…Efficacy of BCG vaccine for pulmonary TB decreases during lifetime and therefore it is more effective against newborns and children (8,9). Additionally, BCG is not recommended for patients with immune deficiency and is not able to control the latent TB infection which can act as reservoir of active TB infection (3). Therefore, several vaccines are in different steps of clinical or preclinical studies.…”

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. 2021

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. Finally, 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 lavage were 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. So, nasal immunization with these formulations, could induce immune responses and considered as new TB vaccine or as BCG booster.

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HspX protein as a candidate vaccine against Mycobacterium tuberculosis: an overview

Cited by 13 publications

References 26 publications

Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs

Mucosal Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens Provides Protection against Mycobacterium tuberculosis in Mice and Guinea Pigs

Enhancement of the Local CD8+ T-Cellular Immune Response to Mycobacterium tuberculosis in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens

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

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