Superior Induction of T Cell Responses to Conserved HIV-1 Regions by Electroporated Alphavirus Replicon DNA Compared to That with Conventional Plasmid DNA Vaccine

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.

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Potent CD4+T Cell Responses Elicited by a Bicistronic HIV-1 DNA Vaccine Expressing gp120 and GM-CSF

The Journal of Immunology ◽

10.4049/jimmunol.168.2.562 ◽

2002 ◽

Vol 168 (2) ◽

pp. 562-568 ◽

Cited By ~ 112

Author(s):

Dan H. Barouch ◽

Sampa Santra ◽

Klara Tenner-Racz ◽

Paul Racz ◽

Marcelo J. Kuroda ◽

...

Keyword(s):

T Cell ◽

Dna Vaccine ◽

T Cell Responses ◽

Cd4 T Cell ◽

Gm Csf ◽

Cell Responses ◽

Hiv 1

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HIV-1 Env DNA Vaccine plus Protein Boost Delivered by EP Expands B- and T-Cell Responses and Neutralizing Phenotype In Vivo

PLoS ONE ◽

10.1371/journal.pone.0084234 ◽

2013 ◽

Vol 8 (12) ◽

pp. e84234 ◽

Cited By ~ 20

Author(s):

Kar Muthumani ◽

Megan C. Wise ◽

Kate E. Broderick ◽

Natalie Hutnick ◽

Jonathan Goodman ◽

...

Keyword(s):

T Cell ◽

Dna Vaccine ◽

T Cell Responses ◽

Cell Responses ◽

Protein Boost ◽

Hiv 1

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A plasmid DNA vaccine encoding prostatic acid phosphatase (PAP) elicits antigen-specific T cells in patients with stage D0 prostate cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.14570 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 14570-14570

Author(s):

D. G. McNeel ◽

E. J. Dunphy ◽

L. E. Johnson ◽

T. P. Frye ◽

M. J. Staab ◽

...

Keyword(s):

Prostate Cancer ◽

T Cell ◽

Dna Vaccine ◽

Plasmid Dna ◽

Prostatic Acid Phosphatase ◽

T Cell Proliferation ◽

Cell Responses ◽

Plasmid Dna Vaccine ◽

Specific Igg ◽

Minimal Residual

14570 Background: Prostatic acid phosphatase (PAP) is a tumor antigen in prostate cancer. Clinical trials conducted in patients with metastatic prostate cancer targeting PAP by means of antigen presenting-cell vaccines have suggested clinical benefit in terms of disease progression and overall survival. Ultimately, tumor vaccines may be most effective in the setting of minimal residual disease. We have been investigating plasmid DNA vaccines encoding PAP in rodent models. We found these to be safe and effective in eliciting PAP-specific CD8 T cells and saw evidence of anti-tumor efficacy. We report here the initial immunological results from a dose-escalation portion of a phase I trial testing a DNA vaccine encoding PAP in patients with minimal residual stage D0 prostate cancer. Methods: Patients with clinical stage D0 prostate cancer with rising PSA were vaccinated over a 12-week period, 6 times at 14-day intervals, with a plasmid DNA vaccine encoding PAP (pTVG-HP). Vaccinations were administered intradermally with 100 mcg, 500 mcg, or 1500 mcg doses, and with 200 mcg of GM-CSF co-administered as a vaccine adjuvant. Immunological responses were evaluated by antigen-specific T cell proliferation and IFNγ secretion, and by ELISA for PAP-specific IgG. Results: At present 9 patients have been enrolled in a dose-escalation portion of the trial, and 6 have completed all immunizations. No serious adverse events have been observed, and no patients have discontinued treatment. To date, immunological analysis has been performed for the first, lowest dose cohort. PAP-specific CD4 and CD8 T cell responses, measured by antigen-specific T cell proliferation, were elicited following immunization in 2 of 3 patients. PAP-specific IgG antibodies were not detectable in these patients following vaccination. Conclusions: Intradermal immunization of patients with stage D0 prostate cancer with pTVG-HP has been without evidence of adverse events in doses up to 500 mcg. CD4 and CD8 T cell responses have been observed, consistent with a predominantly cellular immune response, at even the lowest dose of vaccine. Immunological analysis will be performed for patients completing the other dose levels, and all patients will be followed for changes in serum PSA levels. No significant financial relationships to disclose.

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HIV-1-Based Virus-like Particles that Morphologically Resemble Mature, Infectious HIV-1 Virions

Viruses ◽

10.3390/v11060507 ◽

2019 ◽

Vol 11 (6) ◽

pp. 507 ◽

Cited By ~ 4

Author(s):

Christopher A. Gonelli ◽

Georges Khoury ◽

Rob J. Center ◽

Damian F.J. Purcell

Keyword(s):

T Cell ◽

Dna Vaccine ◽

Neutralizing Antibodies ◽

T Cell Responses ◽

Expression Vectors ◽

Virus Like Particles ◽

Cell Responses ◽

Hiv 1

A prophylactic vaccine eliciting both broad neutralizing antibodies (bNAbs) to the HIV-1 envelope glycoprotein (Env) and strong T cell responses would be optimal for preventing HIV-1 transmissions. Replication incompetent HIV-1 virus-like particles (VLPs) offer the opportunity to present authentic-structured, virion-associated Env to elicit bNAbs, and also stimulate T cell responses. Here, we optimize our DNA vaccine plasmids as VLP expression vectors for efficient Env incorporation and budding. The original vector that was used in human trials inefficiently produced VLPs, but maximized safety by inactivating RNA genome packaging, enzyme functions that are required for integration into the host genome, and deleting accessory proteins Vif, Vpr, and Nef. These original DNA vaccine vectors generated VLPs with incomplete protease-mediated cleavage of Gag and were irregularly sized. Mutations to restore function within the defective genes revealed that several of the reverse transcriptase (RT) deletions mediated this immature phenotype. Here, we made efficient budding, protease-processed, and mature-form VLPs that resembled infectious virions by introducing alternative mutations that completely removed the RT domain, but preserved most other safety mutations. These VLPs, either expressed from DNA vectors in vivo or purified after expression in vitro, are potentially useful immunogens that can be used to elicit antibody responses that target Env on fully infectious HIV-1 virions.

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