Advantage of gene gun-mediated over intramuscular inoculation of plasmid DNA vaccine in reproducible induction of specific immune responses

Yoshida, Atsushi; Nagata, Toshi; Uchijima, Masato; T, Higashi; Koide, Yukio

doi:10.1016/s0264-410x(99)00432-6

Cited by 106 publications

(52 citation statements)

References 17 publications

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“…ϩ T-cell-independent manner (19,27,31). In the current study, taking advantage of the fact that a single epitope-expressing DNA vaccine can induce CTLs without the influence of the other epitopes, we investigated the influence of dominant T-cell responses on subdominant responses.…”

Section: Effector Cd8mentioning

confidence: 99%

Protective Cytotoxic T Lymphocyte Responses Induced by DNA Immunization against Immunodominant and Subdominant Epitopes ofListeria monocytogenesAre Noncompetitive

Yamada¹,

Uchiyama²,

Nagata

et al. 2001

Infect Immun

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Taking advantage of the fact that plasmid DNA encoding a single cytotoxic T lymphocyte (CTL) epitope can induce CTLs, we examined the influence of T-cell responses to dominant epitopes on those to a subdominant epitope derived from Listeria monocytogenes. Our data suggest that interaction between T cells against dominant and subdominant epitopes does not operate in the generation of the hierarchy. Furthermore, we found that a single dominant epitope is sufficient for the induction of protective immunity. Effector CD8ϩ T-cell responses against infection are restricted to a few epitopes compared to the total number of epitopes potentially available (1,2,12,23). These epitopes are termed immunodominant, and cytotoxic T lymphocyte (CTL) responses to subdominant epitopes can be demonstrated in vivo by the removal of dominant epitopes or the separation of dominant and subdominant epitopes so that they are presented on different cells (9,18,21). Various factors have been implicated to determine the position of an epitope in the immunodominant hierarchy: (i) antigen processing efficiency (10,11,20), (ii) transporter associated with antigen processing (TAP)-dependent peptide transport (15), (iii) the affinity of the peptide for the major histocompatibility complex (MHC) molecule (6, 24), (iv) the rate of dissociation of the MHC molecule (26, 28), (v) the transport of MHC-peptide complexes to the cell surface (17), and (vi) the response to the T-cell repertoire (5,7,8).Listeria monocytogenes is a gram-positive bacterium that causes life-threatening infections during pregnancy and in immunocompromised individuals (14). L. monocytogenes enters macrophages and hepatocytes and accesses the cytoplasm by secreting listeriolysin O (LLO), resulting in the induction of a vigorous MHC class I-restricted CTL response that enables the rapid clearance of live bacteria (3, 16). Four different L. monocytogenes epitopes are known to be presented to CTLs by the MHC class I H-2K d molecules (4, 22). These epitopes are derived from bacterial virulent factors, LLO, murein hydrolase p60, and metalloprotease (mpl). Infection of BALB/c mice with a sublethal dose of L. monocytogenes induces dominant CTL responses against LLO 91-99 and p60 217-225 and subdominant responses against p60 449-457 and mpl 84-92. There is no correlation between the amount of epitope that is presented by infected cells and the magnitude of the CTL response (29).We have previously shown that intramuscular or gene gun immunizations with plasmid DNA encoding a single epitope of L. monocytogenes, LLO 91-99, are able to induce specific CTLs in a CD4 ϩ T-cell-independent manner (19, 27, 31). In the current study, taking advantage of the fact that a single epitope-expressing DNA vaccine can induce CTLs without the influence of the other epitopes, we investigated the influence of dominant T-cell responses on subdominant responses.We constructed three plasmids, p91m, p60 217m, and p60 449m, which encode LLO 91-99, p60 217-225, and p60 449-457 of L. monocytogenes, respectively, f...

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Section: Effector Cd8mentioning

confidence: 99%

Protective Cytotoxic T Lymphocyte Responses Induced by DNA Immunization against Immunodominant and Subdominant Epitopes ofListeria monocytogenesAre Noncompetitive

Yamada¹,

Uchiyama²,

Nagata

et al. 2001

Infect Immun

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“…20 Chitosan nanoparticles have the potential to act as mediators of protein antigens or plasmid DNA, and to protect against biological degradation by nucleases. 21,22 Recently, chitosan nanoparticles have also been utilized for sustained release of various drugs, including oligonucleotides. [23][24][25] Studies have shown that chitosan is a promising DNA vector with sustained-releasing ability.…”

Section: Introductionmentioning

confidence: 99%

Preparation and efficacy of Newcastle disease virus DNA vaccine encapsulated in chitosan nanoparticles

Zhao¹,

Zhang²,

Zhang³

et al. 2014

IJN

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Optimal preparation conditions of Newcastle disease virus (NDV) F gene deoxyribonucleic acid (DNA) vaccine encapsulated in chitosan nanoparticles (pFNDV-CS-NPs) were determined. The pFNDV-CS-NPs were prepared according to a complex coacervation method. The pFNDV-CS-NPs were produced with good morphology, high stability, a mean diameter of 199.5 nm, encapsulation efficiency of 98.37%±0.87%, loading capacity of 36.12%±0.19%, and a zeta potential of +12.11 mV. The in vitro release assay showed that the plasmid DNA was sustainably released from the pFNDV-CS-NPs, up to 82.9%±2.9% of the total amount. Cell transfection test indicated that the vaccine expressed the F gene in cells and maintained good bioactivity. Additionally, the safety of mucosal immunity delivery system of the pFNDV-CS-NPs was also tested in vitro by cell cytotoxicity and in vivo by safety test in chickens. In vivo immunization showed that better immune responses of specific pathogen-free chickens immunized with the pFNDV-CS-NPs were induced, and prolonged release of the plasmid DNA was achieved compared to the chickens immunized with the control plasmid. This study lays the foundation for the further development of mucosal vaccines and drugs encapsulated in chitosan nanoparticles.

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“…The latter has been suggested to induce a Th1 milieu with 100-1000 times less amount of DNA than intramuscular injection [29]. However, gene gun bombardment was questioned for allergen immunotherapy by several studies [22,[30][31][32][33].…”

Section: Discussionmentioning

confidence: 99%

A mimotope gene encoding the major IgE epitope of allergen Phl p 5 for epitope-specific immunization

et al. 2009

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A gene vaccine based on a mammalian expression vector containing the sequence of a peptide mimotope of Phl p 5 was constructed. To test whether mimotope gene vaccines can induce allergen-specific antibody responses via molecular mimicry, BALB/c mice were immunized using the mimotope construct with or without a tetanus toxin T-helper epitope. Moreover, intradermal injection was compared to epidermal application via gene gun immunization.Immunization with both mimotope gene constructs elicited allergen-specific antibody responses. As expected, gene gun bombardment induced a Th2-biased immune response, typically associated with IgG1 and IgE antibody production. In contrast, intradermal injection of the vaccine triggered IgG2a antibody expression without any detectable IgE levels, thus biasing the immune response towards Th1. In an RBL assay, mimotope-specific IgG antibodies were able to prevent crosslinking of allergen-specific IgE by Phl p 5. A construct coding for the complete Phl p 5 induced Tcell activation, IFN-γ and IL-4 production. In contrast, the mimotope-DNA construct being devoid of allergen-specific T-cell epitopes had no capacity to activate allergen-specific T cells.Taken together, our data show that it is feasible to induce blocking IgG antibodies with a mimotope-DNA construct when applied intradermally. Thus the mimotope-DNA strategy has two advantages: (1) the avoidance of IgE induction and (2) the avoidance of triggering allergenspecific T-lymphocytes. We therefore suggest that mimotope gene vaccines are potential candidates for epitope-specific immunotherapy of type I allergy.

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Advantage of gene gun-mediated over intramuscular inoculation of plasmid DNA vaccine in reproducible induction of specific immune responses

Cited by 106 publications

References 17 publications

Protective Cytotoxic T Lymphocyte Responses Induced by DNA Immunization against Immunodominant and Subdominant Epitopes ofListeria monocytogenesAre Noncompetitive

Protective Cytotoxic T Lymphocyte Responses Induced by DNA Immunization against Immunodominant and Subdominant Epitopes ofListeria monocytogenesAre Noncompetitive

Preparation and efficacy of Newcastle disease virus DNA vaccine encapsulated in chitosan nanoparticles

A mimotope gene encoding the major IgE epitope of allergen Phl p 5 for epitope-specific immunization

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