scholarly journals Combined Administration with DNA Encoding Vesicular Stomatitis Virus G Protein Enhances DNA Vaccine Potency

2009 ◽  
Vol 84 (5) ◽  
pp. 2331-2339 ◽  
Author(s):  
Chih-Ping Mao ◽  
Chien-Fu Hung ◽  
Tae Heung Kang ◽  
Liangmei He ◽  
Ya-Chea Tsai ◽  
...  
Keyword(s):  
T Cell ◽  
Dna Vaccine ◽  
Vesicular Stomatitis Virus ◽  
Viral Infections ◽  
Dna Vaccines ◽  
T Cell Responses ◽  
Dna Encoding ◽  
Cell Responses ◽  
Prevention And Treatment ◽  
Vesicular Stomatitis

ABSTRACT DNA vaccines have recently emerged at the forefront of approaches to harness the immune system in the prevention and treatment of viral infections, as well as the prevention and treatment of cancers. However, these vaccines suffer from limited efficacy since they often fail to produce significant antigen-specific CD8+ T-cell responses. We report here a novel concept for DNA vaccine design that exploits the unique and powerful ability of viral fusogenic membrane glycoproteins (FMGs) to couple concentrated antigen transfer to dendritic cells (DCs) with local induction of the acute inflammatory response. Intramuscular administration into mice by electroporation technology of a plasmid containing the FMG gene from vesicular stomatitis virus (VSV-G)—together with DNA encoding the E7 protein of human papillomavirus type 16, a model cervical cancer antigen—elicited robust E7-specific CD8+ T-cell responses, as well as therapeutic control of E7-expressing tumors. This effect could potentially be mediated through the immunogenic form of cellular fusion and necrosis induced by VSV-G, which in a concerted fashion provokes leukocyte infiltration into the inoculation site, enhances cross-presentation of antigen to DCs, and stimulates them to mature efficiently. Thus, the incorporation of FMGs into DNA vaccines holds promise for the successful control of viral infections and cancers in the clinic.

scholarly journals Vaccination with a Shigella DNA Vaccine Vector Induces Antigen-Specific CD8+ T Cells and Antiviral Protective Immunity

2001 ◽  
Vol 75 (20) ◽  
pp. 9665-9670 ◽  
Author(s):  
Mohamed T. Shata ◽  
David M. Hone
Keyword(s):  
T Cell ◽  
Dna Vaccine ◽  
Protective Immunity ◽  
Dna Vaccines ◽  
T Cell Responses ◽  
T Cell Response ◽  
Vaccine Vector ◽  
Host Cells ◽  
Cell Responses ◽  
Hiv 1

ABSTRACT A prototype Shigella human immunodeficiency virus type 1 (HIV-1) gp120 DNA vaccine vector was constructed and evaluated for immunogenicity in a murine model. For comparative purposes, mice were also vaccinated with a vaccinia virus-env(vaccinia-env) vector or the gp120 DNA vaccine alone. Enumeration of the CD8+-T-cell responses to gp120 after vaccination using a gamma interferon enzyme-linked spot assay revealed that a single intranasal dose of the Shigella HIV-1 gp120 DNA vaccine vector elicited a CD8+ T-cell response to gp120, the magnitude of which was comparable to the sizes of the analogous responses to gp120 that developed in mice vaccinated intraperitoneally with the vaccinia-env vector or intramuscularly with the gp120 DNA vaccine. In addition, a single dose of the Shigella gp120 DNA vaccine vector afforded significant protection against a vaccinia-env challenge. Moreover, the number of vaccinia-env PFU recovered in mice vaccinated intranasally with the Shigella vector was about fivefold less than the number recovered from mice vaccinated intramuscularly with the gp120 DNA vaccine. Since theShigella vector did not express detectable levels of gp120, this report confirms that Shigella vectors are capable of delivering passenger DNA vaccines to host cells and inducing robust CD8+ T-cell responses to antigens expressed by the DNA vaccines. Furthermore, to our knowledge, this is the first documentation of antiviral protective immunity following vaccination with a live Shigella DNA vaccine vector.

scholarly journals Vesicular Stomatitis Virus Encoding a Destabilized Tumor Antigen Improves Activation of Anti-tumor T Cell Responses

2020 ◽  
Vol 28 (12) ◽  
pp. 2540-2552
Author(s):  
Amanda L. Huff ◽  
Laura Evgin ◽  
Jill Thompson ◽  
Tim Kottke ◽  
Christopher B. Driscoll ◽  
...  
Keyword(s):  
T Cell ◽  
Vesicular Stomatitis Virus ◽  
Tumor Antigen ◽  
T Cell Responses ◽  
Cell Responses ◽  
Vesicular Stomatitis

scholarly journals IL-10 blockade facilitates DNA vaccine-induced T cell responses and enhances clearance of persistent virus infection

2008 ◽  
Vol 205 (3) ◽  
pp. 533-541 ◽  
Author(s):  
David G. Brooks ◽  
Andrew M. Lee ◽  
Heidi Elsaesser ◽  
Dorian B. McGavern ◽  
Michael B.A. Oldstone
Keyword(s):  
T Cell ◽  
Viral Infection ◽  
Dna Vaccine ◽  
Viral Infections ◽  
T Cell Responses ◽  
Lymphocytic Choriomeningitis ◽  
T Cell Immunity ◽  
Therapeutic Vaccination ◽  
Cell Responses ◽  
Cell Immunity

Therapeutic vaccination is a potentially powerful strategy to establish immune control and eradicate persistent viral infections. Large and multifunctional antiviral T cell responses are associated with control of viral persistence; however, for reasons that were mostly unclear, current therapeutic vaccination approaches to restore T cell immunity and control viral infection have been ineffective. Herein, we confirmed that neutralization of the immunosuppressive factor interleukin (IL)-10 stimulated T cell responses and improved control of established persistent lymphocytic choriomeningitis virus (LCMV) infection. Importantly, blockade of IL-10 also allowed an otherwise ineffective therapeutic DNA vaccine to further stimulate antiviral immunity, thereby increasing T cell responses and enhancing clearance of persistent LCMV replication. We therefore propose that a reason that current therapeutic vaccination strategies fail to resurrect/sustain T cell responses is because they do not alleviate the immunosuppressive environment. Consequently, blocking key suppressive factors could render ineffective vaccines more efficient at improving T cell immunity, and thereby allow immune-mediated control of persistent viral infection.

scholarly journals Cellular and Humoral Immunity to Ebola Zaire Glycoprotein and Viral Vector Proteins Following Immunization with Recombinant Vesicular Stomatitis Virus-Based Ebola Vaccine (rVSV∆G-EBOV-GP)

2021 ◽  
Author(s):  
Vanessa N Raabe ◽  
Lilin Lai ◽  
Juliet Morales ◽  
Yongxian Xu ◽  
Nadine Rouphael ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Vesicular Stomatitis Virus ◽  
Matrix Protein ◽  
T Cell Responses ◽  
Memory B Cells ◽  
Post Vaccination ◽  
Cell Responses ◽  
Vesicular Stomatitis ◽  
Nucleoprotein N

While effective at preventing Zaire ebolavirus (EBOV) disease, cellular immunity to EBOV and vector-directed immunity elicited by the recombinant vesicular stomatitis virus expressing Ebola glycoprotein (rVSVΔG-EBOV-GP) vaccine remains poorly understood. Sera and peripheral blood mononuclear cells were collected from 32 participants enrolled in a prospective multicenter study [ClinicalTrials.gov NCT02788227] before vaccination and up to six months post-vaccination. IgM and IgG antibodies, IgG-producing memory B cells, and T cell reactivity to EBOV glycoprotein, vesicular stomatitis virus-Indiana strain (VSV-I) matrix protein, and VSV-I nucleoprotein were measured using ELISA, ELISpot, and intracellular cytokine staining, respectively. Eleven participants previously received a different investigational Ebola vaccine. All participants met positivity criteria for IgG antibodies to, and circulating IgG-producing memory B cells to, EBOV glycoprotein following rVSVΔG-EBOV-GP vaccination. Transient IgM and IgG antibody responses to VSV-I matrix protein (n=1/32 and n=0/32, respectively) and nucleoprotein (n=2/32 and n=1/32, respectively) were infrequently detected, as were IgG-producing memory B cells recognizing VSV-I matrix protein (n=3/31) and nucleoprotein (n=2/31). CD4+ and CD8+ T cell responses to EBOV glycoprotein were present in 15/32 and 19/32 participants at baseline and in 32/32 and 23/32 participants one month post-vaccination, respectively. CD4+ and CD8+ T cell responses to VSV-I matrix protein (n=17/32 and n=16/32, respectively) and VSV-I nucleoprotein (n=23/32 for both CD4+ and CD8+ responses) were common post-vaccination. T cell responses were predominantly mono-cytokine, except CD8+ responses to EBOV glycoprotein among heterologous Ebola vaccine-experienced participants and CD8+ responses to VSV-I nucleoprotein. Overall, rVSVΔG-EBOV-GP elicits robust humoral and memory B cell responses to EBOV glycoprotein in both Ebola vaccine-naïve and heterologous Ebola vaccine-experienced individuals and can generate vector-directed T cell immunity. Further research is needed to understand the significance of pre-existing vector-directed immunity on responses to booster doses of rVSVΔG-EBOV-GP and other rVSV-vectored vaccines.

scholarly journals Pandemic Preparedness Against Influenza: DNA Vaccine for Rapid Relief

2021 ◽  
Vol 12 ◽  
Author(s):  
Tor Kristian Andersen ◽  
Johanna Bodin ◽  
Fredrik Oftung ◽  
Bjarne Bogen ◽  
Siri Mjaaland ◽  
...  
Keyword(s):  
Single Dose ◽  
T Cell ◽  
Dna Vaccine ◽  
Dna Vaccines ◽  
T Cell Responses ◽  
Cytotoxic T Cell ◽  
Pandemic Preparedness ◽  
Vaccine Platform ◽  
Naked Dna ◽  
Cell Responses

The 2009 “swine flu” pandemic outbreak demonstrated the limiting capacity for egg-based vaccines with respect to global vaccine supply within a timely fashion. New vaccine platforms that efficiently can quench pandemic influenza emergences are urgently needed. Since 2009, there has been a profound development of new vaccine platform technologies with respect to prophylactic use in the population, including DNA vaccines. These vaccines are particularly well suited for global pandemic responses as the DNA format is temperature stable and the production process is cheap and rapid. Here, we show that by targeting influenza antigens directly to antigen presenting cells (APC), DNA vaccine efficacy equals that of conventional technologies. A single dose of naked DNA encoding hemagglutinin (HA) from influenza/A/California/2009 (H1N1), linked to a targeting moiety directing the vaccine to major histocompatibility complex class II (MHCII) molecules, raised similar humoral immune responses as the adjuvanted split virion vaccine Pandemrix, widely administered in the 2009 pandemic. Both vaccine formats rapidly induced serum antibodies that could protect mice already 8 days after a single immunization, in contrast to the slower kinetics of a seasonal trivalent inactivated influenza vaccine (TIV). Importantly, the DNA vaccine also elicited cytotoxic T-cell responses that reduced morbidity after vaccination, in contrast to very limited T-cell responses seen after immunization with Pandemrix and TIV. These data demonstrate that DNA vaccines has the potential as a single dose platform vaccine, with rapid protective effects without the need for adjuvant, and confirms the relevance of naked DNA vaccines as candidates for pandemic preparedness.

scholarly journals Oncolytic vesicular stomatitis virus quantitatively and qualitatively improves primary CD8+T-cell responses to anticancer vaccines

2013 ◽  
Vol 2 (8) ◽  
pp. e26013 ◽  
Author(s):  
Byram W Bridle ◽  
Derek Clouthier ◽  
Liang Zhang ◽  
Jonathan Pol ◽  
Lan Chen ◽  
...  
Keyword(s):  
T Cell ◽  
Vesicular Stomatitis Virus ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cell Responses ◽  
Anticancer Vaccines ◽  
Vesicular Stomatitis

scholarly journals Cationic Polymers for the Delivery of the Ebola DNA Vaccine Encoding Artificial T-Cell Immunogen

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 718
Author(s):  
Larisa I. Karpenko ◽  
Evgeny K. Apartsin ◽  
Sergei G. Dudko ◽  
Ekaterina V. Starostina ◽  
Olga N. Kaplina ◽  
...  
Keyword(s):  
T Cell ◽  
Dna Vaccine ◽  
Ebola Virus ◽  
Dna Vaccines ◽  
T Cell Responses ◽  
Negative Control ◽  
Current Data ◽  
Cationic Polymers ◽  
Cell Responses ◽  
Cell Immunity

Background: According to current data, an effective Ebola virus vaccine should induce both humoral and T-cell immunity. In this work, we focused our efforts on methods for delivering artificial T-cell immunogen in the form of a DNA vaccine, using generation 4 polyamidoamine dendrimers (PAMAM G4) and a polyglucin:spermidine conjugate (PG). Methods: Optimal conditions were selected for obtaining complexes of previously developed DNA vaccines with cationic polymers. The sizes, mobility and surface charge of the complexes with PG and PAMAM 4G have been determined. The immunogenicity of the obtained vaccine constructs was investigated in BALB/c mice. Results: It was shown that packaging of DNA vaccine constructs both in the PG envelope and the PAMAM 4G envelope results in an increase in their immunogenicity as compared with the group of mice immunized with the of vector plasmid pcDNA3.1 (a negative control). The highest T-cell responses were shown in mice immunized with complexes of DNA vaccines with PG and these responses significantly exceeded those in the groups of animals immunized with both the combination of naked DNAs and the combination DNAs coated with PAMAM 4G. In the group of animals immunized with complexes of the DNA vaccines with PAMAM 4G, no statistical differences were found in the ability to induce T-cell responses, as compared with the group of mice immunized with the combination of naked DNAs. Conclusions: The PG conjugate can be considered as a promising and safe means to deliver DNA-based vaccines. The use of PAMAM requires further optimization.

scholarly journals DNA Priming Increases Frequency of T-Cell Responses to a Vesicular Stomatitis Virus HIV Vaccine with Specific Enhancement of CD8+ T-Cell Responses by Interleukin-12 Plasmid DNA

2017 ◽  
Vol 24 (11) ◽  
Author(s):  
Shuying S. Li ◽  
Nidhi K. Kochar ◽  
Marnie Elizaga ◽  
Christine M. Hay ◽  
Gregory J. Wilson ◽  
...  
Keyword(s):  
T Cell ◽  
Vesicular Stomatitis Virus ◽  
T Cell Responses ◽  
T Cell Response ◽  
Hiv Vaccine ◽  
Interleukin 12 ◽  
High Dose ◽  
Cell Responses ◽  
Vesicular Stomatitis ◽  
Hiv 1

ABSTRACT The HIV Vaccine Trials Network (HVTN) 087 vaccine trial assessed the effect of increasing doses of pIL-12 (interleukin-12 delivered as plasmid DNA) adjuvant on the immunogenicity of an HIV-1 multiantigen (MAG) DNA vaccine delivered by electroporation and boosted with a vaccine comprising an attenuated vesicular stomatitis virus expressing HIV-1 Gag (VSV-Gag). We randomized 100 healthy adults to receive placebo or 3 mg HIV-MAG DNA vaccine (ProfectusVax HIV-1 gag/pol or ProfectusVax nef/tat/vif, env) coadministered with pIL-12 at 0, 250, 1,000, or 1,500 μg intramuscularly by electroporation at 0, 1, and 3 months followed by intramuscular inoculation with 3.4 × 107 PFU VSV-Gag vaccine at 6 months. Immune responses were assessed after the prime and boost and 6 months after the last vaccination. High-dose pIL-12 increased the magnitude of CD8+ T-cell responses postboost compared to no pIL-12 (P = 0.02), while CD4+ T-cell responses after the prime were higher in the absence of pIL-12 than with low- and medium-dose pIL-12 (P ≤ 0.05). The VSV boost increased Gag-specific CD4+ and CD8+ T-cell responses in all groups (P < 0.001 for CD4+ T cells), inducing a median of four Gag epitopes in responders. Six to 9 months after the boost, responses decreased in magnitude, but CD8+ T-cell response rates were maintained. The addition of a DNA prime dramatically improved responses to the VSV vaccine tested previously in the HVTN 090 trial, leading to broad epitope targeting and maintained CD8+ T-cell response rates at early memory. The addition of high-dose pIL-12 given with a DNA prime by electroporation and boosted with VSV-Gag increased the CD8+ T-cell responses but decreased the CD4+ responses. This approach may be advantageous in reshaping the T-cell responses to a variety of chronic infections or tumors. (This study has been registered at ClinicalTrials.gov under registration no. NCT01578889.)

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