Recent progress in the design of DNA vaccines against tuberculosis

Sefidi-Heris, Youssof; Jahangiri, Abolfazl; Mokhtarzadeh, Ahad; Shahbazi, Mohammad‐Ali; Khalili, Saeed; Baradaran, Behzad; Mosafer, Jafar; Baghbanzadeh, Amir; Hejazi, Maryam; Hashemzaei, Mahmoud; Hamblin, Michael R.; Santos, Hélder A.

doi:10.1016/j.drudis.2020.09.005

Cited by 23 publications

(11 citation statements)

References 141 publications

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“…Nucleic acid vaccines are advantageous due to the relative ease of design, production and scalability. However, no DNA vaccines have progressed beyond preclinical study within the M. tb field—this may be because of their poorly immunogenic nature, or the more complex requirements for vaccine delivery to enter the nucleus and prevent plasmid degradation ( Lee et al, 2018 ; Sefidi-Heris et al, 2020 ). Recently however, the use of tetrafunctional block copolymers to enhance cell uptake of exogenous nucleic acid has improved our ability to effectively deliver DNA vaccines ( Richard-Fiardo et al, 2015 ).…”

Section: Toward the Development Of A Mycobacterium Abscessu...mentioning

confidence: 99%

Virulence Mechanisms of Mycobacterium abscessus: Current Knowledge and Implications for Vaccine Design

et al. 2022

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Mycobacterium abscessus is a member of the non-tuberculous mycobacteria (NTM) group, responsible for chronic infections in individuals with cystic fibrosis (CF) or those otherwise immunocompromised. While viewed traditionally as an opportunistic pathogen, increasing research into M. abscessus in recent years has highlighted its continued evolution into a true pathogen. This is demonstrated through an extensive collection of virulence factors (VFs) possessed by this organism which facilitate survival within the host, particularly in the harsh environment of the CF lung. These include VFs resembling those of other Mycobacteria, and non-mycobacterial VFs, both of which make a notable contribution in shaping M. abscessus interaction with the host. Mycobacterium abscessus continued acquisition of VFs is cause for concern and highlights the need for novel vaccination strategies to combat this pathogen. An effective M. abscessus vaccine must be suitably designed for target populations (i.e., individuals with CF) and incorporate current knowledge on immune correlates of protection against M. abscessus infection. Vaccination strategies must also build upon lessons learned from ongoing efforts to develop novel vaccines for other pathogens, particularly Mycobacterium tuberculosis (M. tb); decades of research into M. tb has provided insight into unconventional and innovative vaccine approaches that may be applied to M. abscessus. Continued research into M. abscessus pathogenesis will be critical for the future development of safe and effective vaccines and therapeutics to reduce global incidence of this emerging pathogen.

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Section: Toward the Development Of A Mycobacterium Abscessu...mentioning

confidence: 99%

Virulence Mechanisms of Mycobacterium abscessus: Current Knowledge and Implications for Vaccine Design

et al. 2022

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“…The literature proposed that a vaccine with the M. tb incubation period antigen as the target antigen would obtain a protective immune response to latent period TB infection, eliminate dormant bacilli, and prevent TB recurrence (15). DNA vaccines expressing latent antigens have also been shown to effectively induce Th1-type immune responses (16,17). In addition, immunotherapy with plasmid DNA has been found to provide effective adjuvant therapy in mice in combination with chemotherapy (18,19).…”

Section: Despite Decades Of Mass Vaccination With the Tuberculosis (T...mentioning

confidence: 99%

B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent Mycobacterium tuberculosis infection

Weng²,

Zhang

et al. 2022

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Latent tuberculosis infection (LTBI) treatment is a notable to accelerate the decline in TB, especially in high-risk populations. Mycobacterium tuberculosis (M. tb) expression profiles differ at different growth periods, and vaccines’ protective and therapeutic effects may increase when they include antigenic compositions from different periods. To develop a post-exposure vaccine that targets LTBI, we constructed four therapeutic DNA vaccines (A39, B37, B31, and B21) using different combinations of proliferating antigens (Ag85A, Ag85B), PE/PPE family antigens (Rv3425), and latent antigens (Rv2029c, Rv1813c, Rv1738). We compared the immunogenicity of the four DNA vaccines in C57BL/6j mice. The B21 vaccine stimulated the strongest cellular immune response, namely Th1/Th17 and CD8+ cytotoxic T lymphocyte responses. It also induced the generation of strengthened effector memory and central memory T cells. In latently infected mice, the B21 vaccine significantly reduced bacterial loads in the spleen and lungs and decreased lung pathology. In conclusion, the B21 DNA vaccine can enhance T cell responses and control reactivation of LTBI.

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“…Therefore, to enhance the immune responses elicited by TB DNA vaccines, it is vital to improve vaccine delivery to the nucleus and optimize the antigen combinations ( Figure 2 ). This stimulates the host immune system to express internalized plasmid DNA via somatic cells, which is subsequently presented to the CD8 + T cells via class I MHC complexes (Sefidi-Heris et al., 2020 ). Hence, the design and development of safe and efficient delivery systems has attracted immense attention in the field of DNA-vaccine development.…”

Section: Introductionmentioning

confidence: 99%

Nanomaterials in tuberculosis DNA vaccine delivery: historical perspective and current landscape

et al. 2022

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Vaccinations, especially DNA vaccines that promote host immunity, are the most effective interventions for tuberculosis (TB) control. However, the vaccine delivery system exhibits a significant impact on the protective effects of the vaccine. Recently, effective nanomaterial-based delivery systems (including nanoparticles, nanogold, nanoliposomes, virus-like particles, and virus carriers) have been developed for DNA vaccines to control TB. This review highlights the historical development of various nanomaterial-based delivery systems for TB DNA vaccines, along with the emerging technologies. Nanomaterial-based vaccine delivery systems could enhance the efficacy of TB vaccination; therefore, this summary could guide nanomaterial selection for optimal and safe vaccine delivery, facilitating the design and development of highly effective TB vaccines.

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Recent progress in the design of DNA vaccines against tuberculosis

Cited by 23 publications

References 141 publications

Virulence Mechanisms of Mycobacterium abscessus: Current Knowledge and Implications for Vaccine Design

Virulence Mechanisms of Mycobacterium abscessus: Current Knowledge and Implications for Vaccine Design

B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent Mycobacterium tuberculosis infection

Nanomaterials in tuberculosis DNA vaccine delivery: historical perspective and current landscape

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