The study of novel DNA vaccines against tuberculosis

Okada, Masaji; Kita, Yoko; Nakajima, Takeshi; Hashimoto, Satomi; Nakatani, Hitoshi; Nishimatsu, Shiho; Nishida, Yasuko; Kanamaru, Noriko; Kaneda, Yudai; Takamori, Yasushi; McMurray, David N.; Tan, Esterlina V.; Cang, Marjorie; Saunderson, Paul; Cruz, Eduardo Canteiro

doi:10.4161/hv.23229

Cited by 7 publications

(7 citation statements)

References 33 publications

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“…9,10 On the other hand, CTL and type I helper T cells are very important for the protective and therapeutic efficacy against TB including MDR-TB and XDR-TB, as reported using several animal models and infectious diseases. [8][9][10][11]18,21,23,24 DNA vaccine is a relatively new approach to immunization for infectious diseases. 2,3,4,[12][13][14][15][16] A hemagglutinating virus of Japan envelope (HVJ-Envelope) using inactivated Sendai virus has been developed, as a nonviral vector for drug delivery.…”

Section: Discussionmentioning

confidence: 99%

“…I. Sugawara (JATA, Tokyo, Japan). 2,10,11 Vaccination a. Administration times and route of the vaccine:…”

Section: Bacteriamentioning

confidence: 99%

“…2 Three weeks after challenge, therapeutic efficacy was measured by enumerating the bacterial loads (CFU) in the liver, spleen and lung. [9][10][11]…”

Section: Bacteriamentioning

confidence: 99%

“…[2][3][4][5][6][7] This vaccine was more efficient than BCG in the murine TBprophylactic model on the basis of the elimination of M. tuberculosis mediated by the induction of CTL and production of IFN-g, as several reports demonstrated that CTL, Th1 cell and IFN-g played a very important role of TB vaccine. [2][3][4][8][9][10][11][12][13][14][15][16][17][18][19] Furthermore, in our previous study, (1) HVJ-E/pcDNA3.1 HSP65 DNA C IL-12 DNA vaccine showed therapeutic efficacy against MDR-TB in mice. (2) Significant prolongation of survival was observed in the XDR-TB infected mice by the treatment with this vaccine.…”

Section: Introductionmentioning

confidence: 99%

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Preclinical study and clinical trial of a novel therapeutic vaccine against multi-drug resistant tuberculosis

Okada

Kita

Hashimoto

et al. 2016

Human Vaccines & Immunotherapeutics

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ABSTRACT[Purpose] Multi-drug resistant (MDR), Mycobacterium tuberculosis (TB) is a big problem in the world. We have developed novel TB therapeutic vaccine (HVJ-E/HSP65 DNA CIL-12 DNA).[Methods and Results] DNA vaccine expressing TB heat shock protein 65 and IL-12 was delivered by the hemagglutinating virus of Japan (HVJ)-envelope. This vaccine provided remarkable protective efficacy and strong therapeutic efficacy against MDR-TB and XDR-TB in murine models. Furthermore, this vaccine provided therapeutic efficacy of prolongation of survival time of TB infected monkeys and augmented the immune responses. Therefore, the preclinical tests were studied for clinical trial. The injection of 100 mg of the vaccine /mouse i.m. three times in two weeks induced significantly strong production of IFN-g and IL-2. 100 mg and 200 mg DNA vaccine/mouse i.m. augmented the production of these cytokines compared with 25 mg DNA vaccine/mouse i. m.. The ratio of 100 mg pDNA to 1AU HVJ-E enhanced the production of IFN-g and IL-2. The decrease in the number of M. tuberculosis in liver of mice was observed by the vaccination of 100mg pDNA. By using these conditions, safety pharmacology study and toxicology test is being studied in monkeys administered by GMP level DNA vaccines. By the toxicology test using monkeys, high dose GMP level vaccine/ monkey is administrated. Safety pharmacological study of repeated administration is also being investigated in GLP level. Furthermore, we have planned to do clinical phase I trial. Targets are human patients with MDR-TB. The safety and tolerability of the vaccine will be evaluated.[Conclusion and recommendations] These data indicate that our novel vaccine might be useful against tuberculosis including XDR-TB and MDR-TB for human therapeutic clinical applications.

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Section: Discussionmentioning

confidence: 99%

“…I. Sugawara (JATA, Tokyo, Japan). 2,10,11 Vaccination a. Administration times and route of the vaccine:…”

Section: Bacteriamentioning

confidence: 99%

“…2 Three weeks after challenge, therapeutic efficacy was measured by enumerating the bacterial loads (CFU) in the liver, spleen and lung. [9][10][11]…”

Section: Bacteriamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Preclinical study and clinical trial of a novel therapeutic vaccine against multi-drug resistant tuberculosis

Okada

Kita

Hashimoto

et al. 2016

Human Vaccines & Immunotherapeutics

Self Cite

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“…A number of mycobacterial proteins including ESAT-6, CFP-10, and Ag85B have been actively explored through subunit and DNA vaccines and have demonstrated improved protection against TB, when compared to the BCG vaccine, in experimental pre-clinical animal models. 7 These candidate vaccines, however, failed to translate to effective protection in subsequent clinical studies. An underexplored TB vaccine candidate is mycolic acid, or cord factor trehalose 6,6′ dimycolate (TDM), a lipid component abundant in the MTB cell wall that is known to strongly stimulate host inflammatory responses and granuloma formation.…”

mentioning

confidence: 99%

Prospective Subunit Nanovaccine against Mycobacterium tuberculosis Infection─Cubosome Lipid Nanocarriers of Cord Factor, Trehalose 6,6′ Dimycolate

Sarkar

Mishra

Selvakannan

et al. 2023

ACS Appl. Mater. Interfaces

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An improved vaccine is urgently needed to replace the now more than 100-year-old Bacillus Calmette−Gueŕin (BCG) vaccine against tuberculosis (TB) disease, which represents a significant burden on global public health. Mycolic acid, or cord factor trehalose 6,6′ dimycolate (TDM), a lipid component abundant in the cell wall of the pathogen Mycobacterium tuberculosis (MTB), has been shown to have strong immunostimulatory activity but remains underexplored due to its high toxicity and poor solubility. Herein, we employed a novel strategy to encapsulate TDM within a cubosome lipid nanocarrier as a potential subunit nanovaccine candidate against TB. This strategy not only increased the solubility and reduced the toxicity of TDM but also elicited a protective immune response to control MTB growth in macrophages. Both pre-treatment and concurrent treatment of the TDM encapsulated in lipid monoolein (MO) cubosomes (MO−TDM) (1 mol %) induced a strong proinflammatory cytokine response in MTB-infected macrophages, due to epigenetic changes at the promoters of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in comparison to the untreated control. Furthermore, treatment with MO−TDM (1 mol %) cubosomes significantly improved antigen processing and presentation capabilities of MTB-infected macrophages to CD4 T cells. The ability of MO−TDM (1 mol %) cubosomes to induce a robust innate and adaptive response in vitro was further supported by a mathematical modeling study predicting the vaccine efficacy in vivo. Overall, these results indicate a strong immunostimulatory effect of TDM when delivered through the lipid nanocarrier, suggesting its potential as a novel TB vaccine.

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Bioinformatics Analysis and Immunogenicity Assessment of the Novel Multi‐Stage DNA Vaccine W541 Against Mycobacterium Tuberculosis

Yang,

Xue,

Wang

et al. 2024

Immunity Inflam & Disease

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BackgroundVaccination is one of the effective measures to prevent latent tuberculosis infection (LTBI) from developing into active tuberculosis (TB). Applying bioinformatics methods to pre‐evaluate the biological characteristics and immunogenicity of vaccines can improve the efficiency of vaccine development.ObjectivesTo evaluate the immunogenicity of TB vaccine W541 and to explore the application of bioinformatics technology in TB vaccine research.MethodsThis study concatenated the immunodominant sequences of Ag85A, Ag85B, Rv3407, and Rv1733c to construct the W541 DNA vaccine. Then, bioinformatics methods were used to analyze the physicochemical properties, antigenicity, allergenicity, toxicity, and population coverage of the vaccine, to identify its epitopes, and to perform molecular docking with MHC alleles and Toll‐like receptor 4 (TLR4) of the host. Finally, the immunogenicity of the vaccine was evaluated in animal experiments.ResultsThe W541 vaccine protein is a soluble cytoplasmic protein with a half‐life of 1.1 h in vivo and an instability index of 45.37. It has good antigenicity and wide population coverage without allergenicity and toxicity. It contains 138 HTL epitopes, 73 CTL epitopes, 8 linear and 14 discontinuous B cell epitopes, and has a strong affinity for TLR4. Immune simulations have shown that it can effectively stimulate innate and adaptive immune responses. Animal experiments confirmed that the W541 DNA vaccine could effectively activate Th1‐ and Th17‐type immune responses, producing high levels of IFN‐γ and IL‐17A, but could not significantly increase antibody levels.ConclusionThe W541 DNA vaccine can induce strong cellular immune responses. However, further optimization of the vaccine design is needed to make the expressed protein more stable in vivo. Bioinformatics analysis could reveal the physicochemical and immunological information of vaccines, which is critical for guiding vaccine design and development.

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The study of novel DNA vaccines against tuberculosis

Abstract: These data indicate that our novel vaccines (HSP65 + IL-12 DNA, granulysin and Ksp37) have a capability to activate the TB-specific CTL and will be very strong protective and therapeutic vaccines against TB.

Cited by 7 publications

References 33 publications

Preclinical study and clinical trial of a novel therapeutic vaccine against multi-drug resistant tuberculosis

Preclinical study and clinical trial of a novel therapeutic vaccine against multi-drug resistant tuberculosis

Prospective Subunit Nanovaccine against Mycobacterium tuberculosis Infection─Cubosome Lipid Nanocarriers of Cord Factor, Trehalose 6,6′ Dimycolate

Bioinformatics Analysis and Immunogenicity Assessment of the Novel Multi‐Stage DNA Vaccine W541 Against Mycobacterium Tuberculosis

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