In vivo electroporation enhances vaccine-mediated therapeutic control of human papilloma virus-associated tumors by the activation of multifunctional and effector memory CD8+ T cells

Sales, Natiely Silva; Silva, Jamile R.; Aps, Luana R.M.M.; Silva, Mariângela O.; Porchia, Bruna F.M.M.; Ferreira, Luís Carlos S.; Diniz, Mariana O.

doi:10.1016/j.vaccine.2017.11.011

Cited by 19 publications

(27 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results are also supported by vaccination studies showing that vaccines eliciting multifunctional CD4 + or CD8 + T-cells ensure better protection against viral infections, e.g., a significant increase in multifunctional T-cells following repeated annual influenza vaccination was recently reported ( 21 – 23 ). Furthermore, HPV-vaccines were illustrated to enhance the control of HPV-associated tumors by activation of multifunctional CD8 + T-cells ( 37 ). This further strengthens our data that multifunctionality of T-cells enhances protection also in pediatric patients and leads to a better control of pathogen-provocation.…”

Section: Discussionmentioning

confidence: 99%

Children From the Age of Three Show a Developmental Switch in T-Cell Differentiation

et al. 2020

View full text Add to dashboard Cite

Every sixth child suffers from hypertrophy of the adenoid, a secondary lymphoid organ, at least once in childhood. Little is known about the impact of pathogen-provocation vs. developmental impact on T-cell responses after 1 year of age. Therefore, developmental and infection-driven influences on the formation of T-cell-compartments and-multifunctionality in adenoids were analyzed taking into account patient's history of age and inflammatory processes. Here, we show that in adenoids of 102 infants and children similar frequencies of naïve, effector, and memory T-cells were accumulated, whereby history of suffering from subsequent infection symptoms resulted in lower frequencies of CD4 + and CD8 + T-cells co-expressing several cytokines. While patients suffering from sole nasal obstruction had balanced Th1-and Th17-compartments, Th1 dominated in patients with concomitant upper airway infections. In addition, analysis of cytokine co-expressing CD4 + and CD8 + T-cells showed that children at the age of three or older differed significantly from those being 1-or 2-years old, implicating a developmental switch in T-cell differentiation at that age. Yet, dissecting age and infectious history of the patients revealed that while CD8 + T-cell differentiation seems to be triggered by development, CD4 + T-cell functionality is partly impaired by infections. However, this functionality recovers by the age of 3 years. Thus, 3 years of age seems to be a critical period in an infant's life to develop robust T-cell compartments of higher quality. These findings identify important areas for future research and distinguish an age period in early childhood when to consider adjusting the choice of treatment of infections.

show abstract

Section: Discussionmentioning

confidence: 99%

Children From the Age of Three Show a Developmental Switch in T-Cell Differentiation

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Different approaches have been developed to increase the immunogenicity of DNA vaccines. Among them are the use of electroporation (53, 54) and the use of plasmids encoding scFv specific for the DEC205 receptor coupled to the antigen of interest.…”

Section: Discussionmentioning

confidence: 99%

Dendritic Cell Targeting Using a DNA Vaccine Induces Specific Antibodies and CD4+ T Cells to the Dengue Virus Envelope Protein Domain III

et al. 2019

View full text Add to dashboard Cite

Dengue fever has become a global threat, causing millions of infections every year. An effective vaccine against all four serotypes of dengue virus (DENV) has not been developed yet. Among the different vaccination strategies available today, DNA vaccines are safe and practical, but currently induce relatively weak immune responses in humans. In order to improve immunogenicity, antigens may be targeted to dendritic cells (DCs), the main antigen presenting cells and orchestrators of the adaptive immune response, inducing T and B cell activation. It was previously shown that a DNA vaccine encoding a fusion protein comprised of an antigen and a single-chain Fv antibody (scFv) specific for the DC endocytic receptor DEC205 induced strong immune responses to the targeted antigen. In this work, we evaluate this strategy to improve the immunogenicity of dengue virus (DENV) proteins. Plasmids encoding the scFv αDEC205, or an isotype control (scFv ISO), fused to the DENV2 envelope protein domain III (EDIII) were generated, and EDIII specific immune responses were evaluated in immunized mice. BALB/c mice were intramuscularly (i.m.) immunized three times with plasmid DNAs encoding either scDEC-EDIII or scISO-EDIII followed by electroporation. Analyses of the antibody responses indicated that EDIII fusion with scFv targeting the DEC205 receptor significantly enhanced serum anti-EDIII IgG titers that inhibited DENV2 infection. Similarly, mice immunized with the scDEC-EDIII plasmid developed a robust CD4+ T cell response to the targeted antigen, allowing the identification of two linear epitopes recognized by the BALB/c haplotype. Taken together, these results indicate that targeting DENV2 EDIII protein to DCs using a DNA vaccine encoding the scFv αDEC205 improves both antibody and CD4+ T cell responses. This strategy opens perspectives for the use of DNA vaccines that encode antigens targeted to DCs as a strategy to increase immunogenicity.

show abstract

“…Electroporation is a potent strategy for increasing drug influx in transcutaneous and intracellular gene delivery and performing high transfection efficiency. Moreover, electroporation can serve as a vaccine adjuvant because it can recruit pro‐inflammatory cells and induce cytokine production at the inoculation site …”

Section: Advanced Technologies For Transcutaneous Gene Deliverymentioning

confidence: 99%

“…By targeting the antigens to the endosomal/lysosomal compartment, antigen processing via the MHC II pathway was enhanced . Electroporation of DNA vaccine pgDE7h encoded the fusion of E7 oncoprotein and HSV‐1 glycoprotein D protein was reported, which effectively enhanced the activation of multifunctional and effector memory CD8+ T cells and promoted antitumor protection against TC‐1 cells expressing E6/E7 …”

Section: Tumor Antigensmentioning

confidence: 99%

Transcutaneous delivery of DNA/mRNA for cancer therapeutic vaccination

Sun

Zeng

Huang

2019

The Journal of Gene Medicine

View full text Add to dashboard Cite

Therapeutic vaccination is a promising strategy for the immunotherapy of cancers. It eradicates cancer cells by evoking and strengthening the patient's own immune system. Because of the easy access and sophisticated immune networks, the skin becomes an ideal target organ for vaccination. Genetic vaccines have been widely investigated, with the advantages of the delivery of multiple antigens and a lower cost for production compared to protein/peptide vaccines. This review summarizes the advances made with respect to the transcutaneous delivery of DNA/mRNA for cancer therapeutic vaccination and also gives a brief description of the immunological milieu of the skin and the importance of dendritic cell‐targeting in vaccine delivery, as well as the technologies that aim to facilitate antigen delivery and modulate antigen‐presenting cells, thus improving cellular responses. The applications of genetic vaccines encoding tumor antigens delivered through the skin route, both in preclinical and clinical trials, are outlined.

show abstract

In vivo electroporation enhances vaccine-mediated therapeutic control of human papilloma virus-associated tumors by the activation of multifunctional and effector memory CD8+ T cells

Cited by 19 publications

References 55 publications

Children From the Age of Three Show a Developmental Switch in T-Cell Differentiation

Children From the Age of Three Show a Developmental Switch in T-Cell Differentiation

Dendritic Cell Targeting Using a DNA Vaccine Induces Specific Antibodies and CD4+ T Cells to the Dengue Virus Envelope Protein Domain III

Transcutaneous delivery of DNA/mRNA for cancer therapeutic vaccination

Contact Info

Product

Resources

About