Phosphorothioated antisense oligodeoxynucleotide suppressing interleukin-10 is a safe and potent vaccine adjuvant

Zhang, Jin; Liu, Ninghua; Lü, Yang; Huang, Zhen; Zang, Yuhui; Chen, Jiangning; Zhang, Junfeng; Ding, Zhi

doi:10.1016/j.vaccine.2019.05.076

Cited by 6 publications

(9 citation statements)

References 37 publications

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“…This result shows that anti Foxp3 ASO mediated greater stimulation of the immune response, suggesting that the inhibition of the suppressive effect of Tregs could have helped to achieve a greater immunogenicity of enolase. Other authors have obtained similar results using other ASOs targeting Tregs [29][30][31][32]. Further studies will be necessary to confirm these findings.…”

Section: Anti-eno Antibodiessupporting

confidence: 70%

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Foxp3 Silencing with Antisense Oligonucleotide Improves Immunogenicity of an Adjuvanted Recombinant Vaccine against Sporothrix schenckii

Batista-Duharte

Sendra

Herrero

et al. 2021

IJMS

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Background: In recent years, there has been great interest in developing molecular adjuvants based on antisense oligonucleotides (ASOs) targeting immunosuppressor pathways with inhibitory effects on regulatory T cells (Tregs) to improve immunogenicity and vaccine efficacy. We aim to evaluate the immunostimulating effect of 2′OMe phosphorothioated Foxp3-targeted ASO in an antifungal adjuvanted recombinant vaccine. Methods: The uptake kinetics of Foxp3 ASO, its cytotoxicity and its ability to deplete Tregs were evaluated in murine splenocytes in vitro. Groups of mice were vaccinated with recombinant enolase (Eno) of Sporothix schenckii in Montanide Gel 01 adjuvant alone or in combination with either 1 µg or 8 µg of Foxp3 ASO. The titers of antigen-specific antibody in serum samples from vaccinated mice (male C57BL/6) were determined by ELISA (enzyme-linked immunosorbent assay). Cultured splenocytes from each group were activated in vitro with Eno and the levels of IFN-γ and IL-12 were also measured by ELISA. The results showed that the anti-Eno antibody titer was significantly higher upon addition of 8 µM Foxp3 ASO in the vaccine formulation compared to the standard vaccine without ASO. In vitro and in vivo experiments suggest that Foxp3 ASO enhances specific immune responses by means of Treg depletion during vaccination. Conclusion: Foxp3 ASO significantly enhances immune responses against co-delivered adjuvanted recombinant Eno vaccine and it has the potential to improve vaccine immunogenicity.

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Section: Anti-eno Antibodiessupporting

confidence: 70%

“…The use of ASOs targeting important regulatory mechanisms is one of the most promising molecular adjuvants for vaccine improvement [16]. Several ASOs have been designed against immunomodulatory components, such as cytokines [29,30],…”

Section: Discussionmentioning

confidence: 99%

Foxp3 Silencing with Antisense Oligonucleotide Improves Immunogenicity of an Adjuvanted Recombinant Vaccine against Sporothrix schenckii

Batista-Duharte

Sendra

Herrero

et al. 2021

IJMS

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“…Several ASOs have been evaluated as adjuvants to enhance the immune response in experimental vaccines. These ASOs were designed against suppressor components such as cytokines [151,152], checkpoints [153,154], or transcription factors [148] (Figure 4). Using a neonatal mouse model of respiratory syncytial virus (RSV) infection, Ripple et al evaluated if local inhibition of IL-4Rα expression using an ASO specific for IL-4Rα during primary RSV infection would prevent Th2-biased responses to secondary RSV infection and improve longterm pulmonary function.…”

Section: Asos As Vaccine Adjuvants In Subunit Vaccinesmentioning

confidence: 99%

“…In a recent report, Zhang et al [152] evaluated the effect of an interleukin 10 (IL-10)-PTO targeted ASO as an immune adjuvant in intradermal vaccination using ovalbumin (OVA), a standard T-dependent antigen. Their results showed that the specific antibody titer of OVA increased 100-fold upon the addition of IL-10 ASO as adjuvant compared to that of OVA alone (p < 0.01).…”

Section: Asos As Vaccine Adjuvants In Subunit Vaccinesmentioning

confidence: 99%

“…Only recently it has been reported that it is possible to successfully use ASOs as part of vaccine formulation for single antigens [151][152][153][154]. This strategy can avoid the administration of systemic higher doses of ASOs, potentially reducing undesired events such as off-target effects and adjuvant-mediated immunotoxicity [157,158].…”

Section: Challenges and Opportunities For Asos Application In Vaccinomentioning

confidence: 99%

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Progress in the Use of Antisense Oligonucleotides for Vaccine Improvement

et al. 2020

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Antisense oligonucleotides (ASOs) are synthetically prepared short single-stranded deoxynucleotide sequences that have been validated as therapeutic agents and as a valuable tool in molecular driving biology. ASOs can block the expression of specific target genes via complementary hybridization to mRNA. Due to their high specificity and well-known mechanism of action, there has been a growing interest in using them for improving vaccine efficacy. Several studies have shown that ASOs can improve the efficacy of vaccines either by inducing antigen modification such as enhanced expression of immunogenic molecules or by targeting certain components of the host immune system to achieve the desired immune response. However, despite their extended use, some problems such as insufficient stability and low cellular delivery have not been sufficiently resolved to achieve effective and safe ASO-based vaccines. In this review, we analyze the molecular bases and the research that has been conducted to demonstrate the potential use of ASOs in vaccines.

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Vaccine-induced effects on regulatory T cell function: autoimmune perspective

Batista-Duharte

2024

Regulatory T Cells and Autoimmune Diseases

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Phosphorothioated antisense oligodeoxynucleotide suppressing interleukin-10 is a safe and potent vaccine adjuvant

Cited by 6 publications

References 37 publications

Foxp3 Silencing with Antisense Oligonucleotide Improves Immunogenicity of an Adjuvanted Recombinant Vaccine against Sporothrix schenckii

Foxp3 Silencing with Antisense Oligonucleotide Improves Immunogenicity of an Adjuvanted Recombinant Vaccine against Sporothrix schenckii

Progress in the Use of Antisense Oligonucleotides for Vaccine Improvement

Vaccine-induced effects on regulatory T cell function: autoimmune perspective

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