DNA vaccines

Robinson, Harriet L.; Torres, Cristina Huebner

doi:10.1006/smim.1997.0083

Cited by 161 publications

(96 citation statements)

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“…DNA vaccines represent a promising strategy for generating antigen-specific immunotherapy because of their simplicity, stability, safety, and capacity for repeated administration [3][4][5][6]7]. Intradermal administration of DNA vaccines by means of a gene gun represents an efficient means of targeting dendritic cells, the most potent professional antigen-presenting cells, which are specialized to prime helper and killer T cells in vivo [8,9].…”

Section: Introductionmentioning

confidence: 99%

A DNA Vaccine Encoding a Codon-Optimized Human Papillomavirus Type 16 E6 Gene Enhances CTL Response and Anti-tumor Activity

Lin

Tsai

et al. 2006

J Biomed Sci

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SummaryThe HPV oncoproteins E6 and E7 are consistently expressed in HPV-associated cancer cells and are responsible for their malignant transformation. Therefore, HPV E6 and E7 are ideal target antigens for developing vaccines and immunotherapeutic strategies against HPV-associated neoplasms. Recently, it has been demonstrated that codon optimization of the HPV-16 E7 gene resulted in highly efficient translation of E7 and increased the immunogenicity of E7-specific DNA vaccines. Since vaccines targeting E6 also represent an important strategy for controlling HPV-associated lesions, we developed a codon-optimized HPV-16 E6 DNA vaccine (pNGVL4a-E6/opt) and characterized the E6-specific CD8 + T cell immune responses as well as the protective and therapeutic anti-tumor effects in vaccinated C57BL/6 mice. Our data indicated that transfection of human embryonic kidney cells (293 cells) with pNGVL4a-E6/opt resulted in highly efficient translation of E6. In addition, vaccination with pNGVL4a-E6/opt significantly enhanced E6-specific CD8 + T cell immune responses in C57BL/6 mice. Mice vaccinated with pNGVL4a-E6/opt are able to generate potent protective and therapeutic antitumor effects against challenge with E6-expressing tumor cell line, TC-1. Thus, DNA vaccines encoding a codon-optimized HPV-16 E6 may be a promising strategy for improving the potency of prophylactic and therapeutic HPV vaccines with potential clinical implications.

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Section: Introductionmentioning

confidence: 99%

A DNA Vaccine Encoding a Codon-Optimized Human Papillomavirus Type 16 E6 Gene Enhances CTL Response and Anti-tumor Activity

Lin

Tsai

et al. 2006

J Biomed Sci

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“…DNA vaccines have been shown to be effective in the induction of immune responses in various animal model systems (31,48,62,63). In particular, their role in priming the immune system has proven to be critical for amplifying antiviral immunity in rhesus macaques (2,3,6,43,48,61).…”

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confidence: 99%

Enhancement of gp120-Specific Immune Responses by Genetic Vaccination with the Human Immunodeficiency Virus Type 1 Envelope Gene Fused to the Gene Coding for Soluble CTLA4

Nayak

Gangadhara

Jabbar

2003

J Virol

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DNA vaccines exploit the inherent abilities of professional antigen-presenting cells to prime the immune system and to elicit immunity against diverse pathogens. In this study, we explored the possibility of augmenting human immunodeficiency virus type 1 gp120-specific immune responses by a DNA vaccine coding for a fusion protein, CTLA4:gp120, in mice. In vitro binding studies revealed that secreted CTLA4:gp120 protein induced a mean florescence intensity shift, when incubated with Raji B cells, indicating its binding to B7 proteins on Raji B cells. Importantly, we instituted three different vaccination regimens to test the efficacy of DNA vaccines encoding gp120 and CTLA4:gp120 in the induction of both cellular (CD8 ؉ ) and antibody responses. Each of the vaccination regimens incorporated a single intramuscular (i.m.) injection of the DNA vaccines to prime the immune system, followed by two booster injections. The i.m.-i.m.-i.m. regimen induced only modest levels of gp120-specific CD8 ؉ T cells, but the antibody response by CTLA4:gp120 DNA was nearly 16-fold higher than that induced by gp120 DNA. In contrast, using the i.m.-subcutaneous (s.c.)-i.m. regimen, it was found that gp120 and CTLA4:gp120 DNAs were capable of inducing significant levels of gp120-specific CD8 ؉ T cells (3.5 and 11%), with antibody titers showing a modest twofold increase for CTLA4:gp120 DNA. In the i.m.-gene gun (g.g.)-g.g. regimen, the mice immunized with gp120 and CTLA4:gp120 harbored gp120-specific CD8؉ T cells at frequencies of 0.9 and 2.9%, with the latter showing an eightfold increase in antibody titers. Thus, covalent antigen modification and the routes of genetic vaccination have the potential to modulate antigen-specific immune responses in mice.DNA vaccines have been shown to be effective in the induction of immune responses in various animal model systems (31,48,62,63). In particular, their role in priming the immune system has proven to be critical for amplifying antiviral immunity in rhesus macaques (2,3,6,43,48,61). Despite the successful application of DNA vaccines to induce immunity, efforts to optimize the efficacy of this mode of antigen delivery are critical to realize the full potential of this vaccine technology (58, 63). There are a number of rate-limiting steps in the pathway of immune induction mediated by DNA vaccines, for example, limited transgene expression and lack of easy access to antigen-presenting cells (APC), especially dendritic cells (DCs). Furthermore, the generation of robust antigen-dependent adaptive immunity appears to be largely dependent on the effective induction of innate immunity by vaccines (5,41,42,56,57,69). DCs have the remarkable ability to link both innate and adaptive immune systems, thereby amplifying antigen-specific immune responses. Although the precise mechanisms of immune induction by DNA vaccines are not fully understood, it is clear that the antigen-processing pathways (both endogenous and exogenous cross-presentation) of APC (DCs) are utilized by DNA-encoded antigens to elicit...

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“…DNA (plasmid)-based immunization induces host humoral and cellular immune responses (1,3,5,12,13,31,39,43). Because antigens encoded by plasmid DNA vaccines are produced in the host, the antigens retain their natural form, unlike those of attenuated whole-organism vaccines, which are denatured and modified.…”

mentioning

confidence: 99%

Papillomavirus Pseudovirus: a Novel Vaccine To Induce Mucosal and Systemic Cytotoxic T-Lymphocyte Responses

Shi

Liu

Huang

et al. 2001

J Virol

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Intestinal mucosa is a portal for many infectious pathogens. Systemic immunization, in general, does not induce a cytotoxic T-lymphocyte (CTL) response at the mucosal surface. Because papillomavirus (PV) naturally infects mucosa and skin, we determined whether PV pseudovirus, i.e., PV-like particles in which unrelated DNA plasmids are packaged, could generate specific mucosal immunity. We found that the pseudovirus that encoded the lymphocytic choriomeningitis virus gp33 epitope induced a stronger CTL response than a DNA vaccine (plasmid) encoding the same epitope given systemically. The virus-like particles that were used to make the pseudoviruses provided an adjuvant effect for induction of CTLs by the DNA vaccine. The PV pseudovirus pseudoinfected mucosal and systemic lymphoid tissues when administered orally. Oral immunization with the pseudovirus encoding human PV type 16 mutant E7 induced mucosal and systemic CTL responses. In comparison, a DNA vaccine encoding E7, when given orally, did not induce a CTL response in intestinal mucosal lymphoid tissue. Further, oral immunization with the human PV pseudovirus encoding E7 protected mice against mucosal challenge with an E7-expressing bovine PV pseudovirus. Thus, PV pseudovirus can be used as a novel vaccine to induce mucosal and systemic CTL responses.

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DNA vaccines

Cited by 161 publications

References 0 publications

A DNA Vaccine Encoding a Codon-Optimized Human Papillomavirus Type 16 E6 Gene Enhances CTL Response and Anti-tumor Activity

A DNA Vaccine Encoding a Codon-Optimized Human Papillomavirus Type 16 E6 Gene Enhances CTL Response and Anti-tumor Activity

Enhancement of gp120-Specific Immune Responses by Genetic Vaccination with the Human Immunodeficiency Virus Type 1 Envelope Gene Fused to the Gene Coding for Soluble CTLA4

Papillomavirus Pseudovirus: a Novel Vaccine To Induce Mucosal and Systemic Cytotoxic T-Lymphocyte Responses

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