Protection against tuberculosis by a plasmid DNA vaccine

Lowrie, D B; Silva, Célio Lopes; Colston, M. J.; Ragno, S.; Tascon, Ricardo E.

doi:10.1016/s0264-410x(97)00073-x

Cited by 147 publications

(99 citation statements)

References 6 publications

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“…23 Despite the success of naked DNA-hsp65-based vaccine to protect BALB/c mice against tuberculosis, it requires multiple doses of high amounts of plasmid for effective immunization. 7 To optimize this DNA vaccine, we used an approach where adjuvants with targeting and immunostimulatory properties prepared by microencapsulation techniques are administered in conjunction with the DNA-encoding antigen.…”

Section: Discussionmentioning

confidence: 99%

“…3,4 Vaccination by intramuscular injection of naked plasmid DNA encoding mycobacterial 65 kDa heat shock protein (hsp65) protected BALB/c mice against subsequent challenge with virulent Mycobacterium tuberculosis H37Rv strain. [5][6][7] Protection was attributed to the establishment of a cellular immune response dominated by antigen-specific T lymphocytes (TL) that both produced interferon-g and were cytotoxic towards infected cells. 8 In addition, in heavily infected mice, vaccination with hsp65-encoding DNA can switch the immune response from one that is relatively inefficient and produces bacterial stasis to one that kills bacteria, presenting pronounced therapeutic action.…”

Section: Introductionmentioning

confidence: 99%

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Single dose of a vaccine based on DNA encoding mycobacterial hsp65 protein plus TDM-loaded PLGA microspheres protects mice against a virulent strain of Mycobacterium tuberculosis

et al. 2003

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The high incidence of tuberculosis around the world and the inability of BCG to protect certain populations clearly indicate that an improved vaccine against tuberculosis is needed. A single antigen, the mycobacterial heat shock protein hsp65, is sufficient to protect BALB/c mice against challenge infection when administered as DNA vaccine in a threedose-based schedule. In order to simplify the vaccination schedule, we coencapsulated hsp65-DNA and trehalose dimicolate (TDM) into biodegradable poly(DL-lactide-co-glycolide) (PLGA) microspheres. BALB/c mice immunized with a single dose of DNA-hsp65/TDM-loaded microspheres produced high levels of IgG2a subtype antibody and high amounts of IFN-g in the supernatant of spleen cell cultures. DNA-hsp65/TDM-loaded microspheres were also able to induce high IFN-g production in bulk lung cells from challenged mice and confer protection as effective as that attained after three doses of naked DNA administration. This new formulation also allowed a ten-fold reduction in the DNA dose when compared to naked DNA. Thus, this combination of DNA vaccine and adjuvants with immunomodulatory and carrier properties holds the potential for an improved vaccine against tuberculosis. Gene Therapy (2003) 10, 678-685.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Single dose of a vaccine based on DNA encoding mycobacterial hsp65 protein plus TDM-loaded PLGA microspheres protects mice against a virulent strain of Mycobacterium tuberculosis

et al. 2003

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“…The use of the DNA-hsp65 vaccine showed an important prophylactic and therapeutic effect in vivo against tuberculosis. 24,25 This vaccine also induced upregulation of MHC class I and class II molecules on macrophages. 26,27 Moreover, different groups have found that mycobacterial hsp65 gene transfer can elicit a profound antitumoral effect.…”

Section: Introductionmentioning

confidence: 96%

“…However, preclinical data from our group and others using different animal models show no evidence of autoimmune disease when DNA-hsp65 was used for immunization. [24][25][26]30 It is relevant to point that the immunogenicity of tumor-derived HSP-peptide complexes has been shown to be individually tumor specific and not tumor-type specific. This suggests that the relevant immunoprotective peptides are most likely derived from individual tumorspecific antigens rather than from shared tumor antigens.…”

Section: Introductionmentioning

confidence: 99%

Phase I trial of DNA-hsp65 immunotherapy for advanced squamous cell carcinoma of the head and neck

et al. 2008

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Considering that mycobacterial heat-shock protein 65 (hsp65) gene transfer can elicit a profound antitumoral effect, this study aimed to establish the safety, maximum-tolerated dose (MTD) and preliminary efficacy of DNA-hsp65 immunotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC). For this purpose, 21 patients with unresectable and recurrent HNSCC were studied. Each patient received three ultrasound-guided injections at 21-day intervals of: 150, 600 or 400 mg of DNA-hsp65. Toxicity was graded according to CTCAE directions. Tumor volume was measured before and after treatment using computed tomography scan. The evaluation included tumor mass variation, delayed-type hypersensitivity response and spontaneous peripheral blood mononuclear cell proliferation before and after treatment. The MTD was 400 mg per dose. DNAhsp65 immunotherapy was well tolerated with moderate pain, edema and infections as the most frequent adverse effects. None of the patients showed clinical or laboratory alterations compatible with autoimmune reactions. Partial response was observed in 4 out of 14 patients who completed treatment, 2 of which are still alive more than 3 years after the completion of the trial. Therefore, DNA-hsp65 immunotherapy is a feasible and safe approach at the dose of 400 mg per injection in patients with HNSCC refractory to standard treatment. Further studies in a larger number of patients are needed to confirm the efficacy of this novel strategy.

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“…Prophylactic DNA vaccines expressing M. tuberculosis antigens or cytokines are of particular interest, because of their efficiency and long-lasting effect in animal TB models. For example, prophylactic DNA vaccines expressing various M. tuberculosis antigens, including Ag85A, [15][16][17] Ag85B, 17,18 65 kDa heat shock protein, 19,20 and PstS-3 21 , were found to be effective at limiting the growth of M. tuberculosis in mice. In contrast, there has been little evidence that DNA vaccines are useful as therapeutic vaccines against TB.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic effect of DNA vaccines combined with chemotherapy in a latent infection model after aerosol infection of mice with Mycobacterium tuberculosis

Jeon

Kim

et al. 2003

Gene Ther

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Protection against tuberculosis by a plasmid DNA vaccine

Cited by 147 publications

References 6 publications

Single dose of a vaccine based on DNA encoding mycobacterial hsp65 protein plus TDM-loaded PLGA microspheres protects mice against a virulent strain of Mycobacterium tuberculosis

Single dose of a vaccine based on DNA encoding mycobacterial hsp65 protein plus TDM-loaded PLGA microspheres protects mice against a virulent strain of Mycobacterium tuberculosis

Phase I trial of DNA-hsp65 immunotherapy for advanced squamous cell carcinoma of the head and neck

Therapeutic effect of DNA vaccines combined with chemotherapy in a latent infection model after aerosol infection of mice with Mycobacterium tuberculosis

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