Fast DNA Vaccination Strategy Elicits a Stronger Immune Response Dependent on CD8+CD11c+ Cell Accumulation

Conventional DNA vaccine strategies usually employ a regimen of immunizations at 2-week or longer intervals to induce effective memory cell-dependent immune responses. Clinical cancer treatment requires a faster immunization strategy to contend with tumor progression. In this study, a novel fast immunization strategy was established, wherein a DNA vaccine was intramuscularly administered on days 0, 2, and 5 in a murine lung cancer model. Effector cells peaked 7 to 10 days after the last vaccination. Compared with traditional 2-week-interval immunization strategies, antigen-specific cytolysis and INF-γ secretion were significantly enhanced under the fast vaccination approach. As a result, the rapidly administered DNA vaccine elicited stronger and more prompt antitumor effects. The probable underlying mechanism of fast immunization was the accumulation of CD8+CD11c+ antigen-presenting cells at the injection site, which enhanced subsequent antigen presentation. In conclusion, the fast DNA vaccination strategy shortened vaccination time to 5 days and elicited a stronger antitumor immune response.

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CXCR4 antagonist (BL-8040) to enhance antitumor effects by increasing tumor infiltration of antigen-specific effector T-cells.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.5_suppl.73 ◽

2018 ◽

Vol 36 (5_suppl) ◽

pp. 73-73 ◽

Cited By ~ 4

Author(s):

Pankaj Gaur ◽

Vivek Verma ◽

Seema Gupta ◽

Ella Sorani ◽

Abi Vainstein Haras ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Tumor Growth ◽

Progenitor Cells ◽

Specific Antigen ◽

Mouse Tumor ◽

Cxcr4 Antagonist ◽

Antitumor Effects ◽

Hematopoietic Stem ◽

Effector Cells

73 Background: C-X-C chemokine receptor type 4 (CXCR4) helps to retain the hematopoietic stem cells (HSC) in the bone marrow (BM). CXCR4 binds to its ligand CXCL12/SDF1 which is constitutively expressed in the BM thereby inhibiting the mobilization of CXCR4 expressing immune progenitor cells. Moreover, increased numbers of effector cells in the tumor microenvironment (TME) are directly correlated to enhanced immunotherapeutic efficacy. Therefore, we hypothesized that CXCR4 antagonism will result in movement of immune progenitor cells from BM to periphery leading to increased availability of T-cells in the periphery and better infiltration of effector cells into the TME. Methods: In TC-1 mouse tumor-model, we tested the effects of CXCR4 antagonist (BL-8040; 4 doses; 24 h apart; 20 mg/kg) on the tumor growth and mice survival in the presence of tumor-specific antigen priming using E7 peptide vaccine (3 doses, one week apart). Anti-tumor immune responses were determined in the tumor tissues obtained 3-4 days after the second vaccination using flow cytometry. Results: We found that BL-8040 given with specific antigenic stimulation results in significantly enhanced anti-tumor immune response, leading to a decrease in tumor growth (p≤0.001 at day 21) and prolonged mice survival. At day 35 after tumor implantation, 80% of mice survived in the BL-8040 + vaccine treatment group compared to 0% survival following BL-8040 or vaccine treatments. Interestingly, we also found that BL-8040 leads to a significant increase in the numbers of antigen-specific CD8+ T-cells in the TME. We also found that starting BL-8040 prior to or together with the priming of the mice did not affect the outcome, suggesting that the scheduling of BL-8040 does not affect the therapeutic outcomes. Conclusions: These results suggest that BL-8040 treatment enhances anti-tumor immune response by potentially increasing the immune progenitor cells in the periphery leading to a better immune response. These results also suggest that BL-8040, a CXCR4 antagonist, is a promising immune-modulatory agent with potent anti-tumor effects.

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DNA vaccination strategy targets epidermal dendritic cells, initiating their migration and induction of a host immune response

Molecular Therapy — Methods & Clinical Development ◽

10.1038/mtm.2014.54 ◽

2014 ◽

Vol 1 ◽

pp. 14054 ◽

Cited By ~ 16

Author(s):

Trevor RF Smith ◽

Katherine Schultheis ◽

William B Kiosses ◽

Dinah H Amante ◽

Janess M Mendoza ◽

...

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Vaccination Strategy ◽

Host Immune Response ◽

Dna Vaccination ◽

Epidermal Dendritic Cells

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β-Glucan Oligosaccharide EnhancesCD8+T Cells Immune Response Induced by a DNA Vaccine Encoding Hepatitis B Virus Core Antigen

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/645213 ◽

2010 ◽

Vol 2010 ◽

pp. 1-10 ◽

Cited By ~ 10

Author(s):

Jing Wang ◽

Shengfu Dong ◽

Chunhong Liu ◽

Wei Wang ◽

Shuhui Sun ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

T Cell ◽

Dna Vaccine ◽

Dna Vaccination ◽

T Cell Response ◽

Basic Unit ◽

Cell Immune Response ◽

Core Antigen ◽

Human Beings

DNA vaccination can induce specificCD8+T cell immune response, but the response level is low in large mammals and human beings. Coadministration of an adjuvant can optimize protective immunity elicited by a DNA vaccine. In this study, we investigated the effect of a synthetic glucohexaose (β-glu6), an analogue of Lentinan basic unit, on specificCD8+T cell response induced by a DNA vaccine encoding HBcAg (pB144) in mice. We found thatβ-glu6 promoted the recruitment and maturation of dendritic cells, enhanced the activation ofCD8+andCD4+T cells and increased the number of specificCD8+/IFN-γ+T cells in lymphoid and nonlymphoid tissues in mice immunized by pB144. Immunization with pB144 andβ-glu6 increased the anti-HBc IgG and IgG2a antibody titer. These results demonstrate thatβ-glu6 can enhance the virus-specific CTL and Th1 responses induced by DNA vaccine, suggestingβ-glu6 as a candidate adjuvant in DNA vaccination.

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Faculty Opinions recommendation of Genetic Immunization With In Vivo Dendritic Cell-targeting Liposomal DNA Vaccine Carrier Induces Long-lasting Antitumor Immune Response.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726015290.793515733 ◽

2016 ◽

Author(s):

Miguel Vicente-Manzanares

Keyword(s):

Immune Response ◽

Dendritic Cell ◽

Dna Vaccine ◽

Antitumor Immune Response ◽

Cell Targeting ◽

Genetic Immunization ◽

Vaccine Carrier

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Vaccination strategy and anti - SARS-CoV-2 S titers in healthcare workers of the INT – IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy)

Infectious Agents and Cancer ◽

10.1186/s13027-021-00375-2 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Ernesta Cavalcanti ◽

Maria Antonietta Isgrò ◽

Domenica Rea ◽

Lucia Di Capua ◽

Giusy Trillò ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Healthcare Workers ◽

Geometric Mean ◽

Vaccination Strategy ◽

Antibody Responses ◽

Cancer Center ◽

Serum Samples ◽

Humoral Immune ◽

History Of

Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally, requiring the development of billions of different vaccine doses. The SARS-CoV-2 spike mRNA vaccine (named BNT162b2/Pfizer), authorized by the FDA, has shown high efficacy in preventing SARS-CoV-2 infection after administration of two doses in individuals 16 years of age and older. In the present study, we retrospectively evaluated the differences in the SARS-CoV-2 humoral immune response after vaccine administration in the two different cohorts of workers at the INT - IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy): previously infected to SARS-CoV-2 subjects and not infected to SARS-CoV-2 subjects. Methods We determined specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S immunoassay in serum samples of 35 healthcare workers with a previous documented history of SARS-CoV-2 infection and 158 healthcare workers without, after 1 and 2 doses of vaccine, respectively. Moreover, geometric mean titers and relative fold changes (FC) were calculated. Results Both previously infected and not infected to SARS-CoV-2 subjects developed significant immune responses to SARS-CoV-2 after the administration of 1 and 2 doses of vaccine, respectively. Anti-S antibody responses to the first dose of vaccine were significantly higher in previously SARS-CoV-2-infected subjects in comparison to titers of not infected subjects after the first as well as the second dose of vaccine. Fold changes for subjects previously infected to SARS-CoV-2 was very modest, given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for naïve subjects, mean fold change following the first dose was low ($$ \overline{x} $$ x ¯ =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose. Conclusions The results showed that, as early as the first dose, SARS-CoV-2-infected individuals developed a remarkable and statistically significant immune response in comparison to those who did not contract the virus previously, suggesting the possibility of administering only one dose in previously SARS-CoV-2-infected subjects. FC for previously infected subjects should not be taken into account for the generally high pre-vaccination values. Conversely, FC for not infected subjects, after the second dose, were = 3.8 in > 45.0% of vaccinees, and ≤ 3.1 in 19.0%, the latter showing a potential susceptibility to further SARS-CoV-2 infection.

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Development of species-specific IgM antibodies and elevation of mucosal immune response in Labeo rohita using recombinant bicistronic nano DNA vaccine priming

Fish & Shellfish Immunology ◽

10.1016/j.fsi.2021.04.008 ◽

2021 ◽

Vol 113 ◽

pp. 185-195

Author(s):

Tasok Leya ◽

Irshad Ahmad ◽

Rajendran Kooloth Valappil ◽

Pani Prasad Kurcheti ◽

Gayatri Tripathi ◽

...

Keyword(s):

Immune Response ◽

Dna Vaccine ◽

Labeo Rohita ◽

Mucosal Immune Response ◽

Igm Antibodies ◽

Species Specific

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Influence of icariin on inflammation, apoptosis, invasion, and tumor immunity in cervical cancer by reducing the TLR4/MyD88/NF-κB and Wnt/β-catenin pathways

Cancer Cell International ◽

10.1186/s12935-021-01910-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chunyang Li ◽

Shuangqing Yang ◽

Huaqing Ma ◽

Mengjia Ruan ◽

Luyan Fang ◽

...

Keyword(s):

Cervical Cancer ◽

Underlying Mechanism ◽

Tissue Growth ◽

Migration And Invasion ◽

Dependent Manner ◽

Antitumor Effects ◽

Siha Cells ◽

Cervical Cancer Cells

Abstract Background Cervical cancer is a type of the most common gynecology tumor in women of the whole world. Accumulating data have shown that icariin (ICA), a natural compound, has anti-cancer activity in different cancers, including cervical cancer. The study aimed to reveal the antitumor effects and the possible underlying mechanism of ICA in U14 tumor-bearing mice and SiHa cells. Methods The antitumor effects of ICA were investigated in vivo and in vitro. The expression of TLR4/MyD88/NF-κB and Wnt/β-catenin signaling pathways were evaluated. Results We found that ICA significantly suppressed tumor tissue growth and SiHa cells viability in a dose-dependent manner. Also, ICA enhanced the anti-tumor humoral immunity in vivo. Moreover, ICA significantly improved the composition of the microbiota in mice models. Additionally, the results clarified that ICA significantly inhibited the migration, invasion capacity, and expression levels of TGF-β1, TNF-α, IL-6, IL-17A, IL-10 in SiHa cells. Meanwhile, ICA was revealed to promote the apoptosis of cervical cancer cells by down-regulating Ki67, survivin, Bcl-2, c-Myc, and up-regulating P16, P53, Bax levels in vivo and in vitro. For the part of mechanism exploration, we showed that ICA inhibits the inflammation, proliferation, migration, and invasion, as well as promotes apoptosis and immunity in cervical cancer through impairment of TLR4/MyD88/NF-κB and Wnt/β-catenin pathways. Conclusions Taken together, ICA could be a potential supplementary agent for cervical cancer treatment.

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Non-Lethal Sequential Individual Monitoring of Viremia in Relation to DNA Vaccination in Fish–Example Using a Salmon Alphavirus DNA Vaccine in Atlantic Salmon Salmo salar

Vaccines ◽

10.3390/vaccines9020163 ◽

2021 ◽

Vol 9 (2) ◽

pp. 163

Author(s):

Catherine Collins ◽

Katherine Lester ◽

Jorge Del-Pozo ◽

Bertrand Collet

Keyword(s):

Dna Vaccine ◽

Experimental Infection ◽

Vaccine Efficacy ◽

Dna Vaccines ◽

Experimental Studies ◽

Dna Vaccination ◽

Line System ◽

Individual Fish ◽

Antibody Levels ◽

Subtype 3

Traditionally, commercial testing for vaccine efficacy has relied on the mass infection of vaccinated and unvaccinated animals and the comparison of mortality prevalence and incidence. For some infection models where disease does not cause mortality this approach to testing vaccine efficacy is not useful. Additionally, in fish experimental studies on vaccine efficacy and immune response the norm is that several individuals are lethally sampled at sequential timepoints, and results are extrapolated to represent the kinetics of immune and disease parameters of an individual fish over the entire experimental infection period. In the present study we developed a new approach to vaccine testing for viremic viruses in fish by following the same individuals over the course of a DNA vaccination and experimental infection through repeated blood collection and analyses. Injectable DNA vaccines are particularly efficient against viral disease in fish. To date, two DNA vaccines have been authorised for use in fish farming, one in Canada against Infectious Haemorrhagic Necrotic virus and more recently one in Europe against Salmon Pancreatic Disease virus (SPDv) subtype 3. In the current study we engineered and used an experimental DNA vaccine against SPDv subtype 1. We measured viremia using a reporter cell line system and demonstrated that the viremia phase was completely extinguished following DNA vaccination. Differences in viremia infection kinetics between fish in the placebo group could be related to subsequent antibody levels in the individual fish, with higher antibody levels at terminal sampling in fish showing earlier viremia peaks. The results indicate that sequential non-lethal sampling can highlight associations between infection traits and immune responses measured at asynchronous timepoints and, can provide biological explanations for variation in data. Similar to results observed for the SPDv subtype 3 DNA vaccine, the SPDv subtype 1 DNA vaccine also induced an interferon type 1 response after vaccination and provided high protection against SPDv under laboratory conditions when fish were challenged at 7 weeks post-vaccination.

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Beneficial Actions of Orostachys japonica and Its Compounds against Tumors via MAPK Signaling Pathways

Nutrients ◽

10.3390/nu13020555 ◽

2021 ◽

Vol 13 (2) ◽

pp. 555

Author(s):

Soyoung Hur ◽

Eungyeong Jang ◽

Jang-Hoon Lee

Keyword(s):

Molecular Mechanisms ◽

Epithelial To Mesenchymal Transition ◽

Malignant Tumors ◽

Treatment Options ◽

Underlying Mechanism ◽

Mapk Signaling ◽

Mitogen Activated Protein Kinase ◽

Antitumor Effects ◽

Mesenchymal Transition ◽

Perennial Plant

Tumors are one of the most life-threatening diseases, and a variety of cancer treatment options have been continuously introduced in order to overcome cancer and improve conventional therapy. Orostachys japonica (O. japonica), which is a perennial plant belonging to the genus Orostachys of the Crassulaceae family, has been revealed to exhibit pharmacological properties against various tumors in numerous studies. The present review aimed to discuss the biological actions and underlying molecular mechanisms of O. japonica and its representative compounds—kaempferol and quercetin—against tumors. O. japonica reportedly has antiproliferative, anti-angiogenic, and antimetastatic activities against various types of malignant tumors through the induction of apoptosis and cell cycle arrest, a blockade of downstream vascular endothelial growth factor (VEGF)-VEGFR2 pathways, and the regulation of epithelial-to-mesenchymal transition. In addition, emerging studies have highlighted the antitumor efficacy of kaempferol and quercetin. Interestingly, it was found that alterations of the mitogen-activated protein kinase (MAPK) signaling cascades are involved in the pivotal mechanisms of the antitumor effects of O. japonica and its two compounds against cancer cell overgrowth, angiogenesis, and metastasis. In summary, O. japonica could be considered a preventive and therapeutic medicinal plant which exhibits antitumor actions by reversing altered patterns of MAPK cascades, and kaempferol and quercetin might be potential components that can contribute to the efficacy and underlying mechanism of O. japonica.

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