Characterization of humoral immune responses induced by an influenza hemagglutinin DNA vaccine

Deck, R. Randall; DeWitt, Corrille M.; Donnelly, John; Liu, Margaret A.; Ulmer, Jeffrey B.

doi:10.1016/s0264-410x(96)00101-6

Cited by 134 publications

(60 citation statements)

References 27 publications

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“…The number of peptide-specific T cells was well maintained for long periods with only limited variation between hosts. In a number of experimental systems, long-term persistence of humoral immunity has been reported, [2][3][4] in accordance with our results in measurement of antibodies reactive with truncated HER2 protein encoded by plasmids for vaccines. The persistent immunity has been accounted for by either long-term maintenance of genes encoded by plasmids in myocytes or of synthesized antigen molecules 5 rather than cDNA, or by maintenance of memory lymphocytes specific for the cognate target antigens.…”

Section: Discussionsupporting

confidence: 91%

“…Spleen cells from mice at 3 weeks after the final immunization were treated with ACK lysis buffer (0.15 M NH 4 Cl, 1 mM KHCO 3 , and 0.1 mM Na 2 EDTA, pH 7.2) to remove erythrocytes. Spleen cells (5 × 10 6 ) were co-cultured with 5 × 10 5 mitomycin C (MMC)-treated CMS17HE cells in RPMI 1640 (GIBCO BRL, Grand Island, NY, USA) with 10% fetal calf serum (FCS) (Intergen, Purchase, NY, USA), 2-mercaptoethanol (50 M), penicillin (100 units/ml), streptomycin (100 g/ml), and 20 IU/ml recombinant human IL-2 (rIL-2, Takeda Pharmaceutical, Tokyo, Japan) in 24-well plates at 37°C in 5% CO 2 .…”

Section: Generation Of Ctl Effector Cells and Target Cellsmentioning

confidence: 99%

“…In many systems in mice, antibodies against molecules encoded by cDNA in plasmids remain detectable for more than 1 year after the last immunization. [2][3][4] This can be explained by persistent antigen expression by the DNA-transduced cells, including professional antigenpresenting cells such as dendritic cells, and by persistent memory cells. 5,6 This is an extremely important feature beneficial for constructing vaccines against a variety of infectious agents.…”

Section: Introductionmentioning

confidence: 99%

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HER2 peptide-specific CD8+ T cells are proportionally detectable long after multiple DNA vaccinations

et al. 2002

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Section: Discussionsupporting

confidence: 91%

Section: Generation Of Ctl Effector Cells and Target Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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HER2 peptide-specific CD8+ T cells are proportionally detectable long after multiple DNA vaccinations

et al. 2002

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“…Furthermore, persistent expression of the encoded antigen by DNA vaccines would be expected to induce a long-lived immunity. Indeed, mice that received a single injection of plasmid encoding hepatitis B surface antigen or haemagglutinin developed high levels of speci®c antibodies that persisted for at least 1 year without signi®cant reduction in titres [23,24]. Interestingly, DNA vaccines initially designed to prevent infection could also have a pronounced ), pCMV-tPA/GroEL (IM-tPA/GroEL, 2j2, or GG-tPA/GroEL, 2d2), or control plasmids pCMV-link (IM-Km, 2r2, or GG-Km, ÐÐ).…”

Section: Discussionmentioning

confidence: 99%

Induction of a Th1-type of immune response but not protective immunity by intramuscular DNA immunisation with Brucella abortus GroEL heat-shock gene

Leclerq¹,

Harms²,

Rosinha³

et al. 2002

Journal of Medical Microbiology

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The immunogenicity and protective ef®cacy of a DNA vaccine encoding the GroEL heatshock gene from Brucella abortus was tested in BALB/c mice immunised by intramuscular (i.m.) needle injection or epidermally by gene gun. The Brucella GroEL gene was ampli®ed by PCR and cloned into two different mammalian expression vectors pCMV-link and pCMV-tPA. The D17 cell line was transfected with both constructs and GroEL transcripts were detected by Northern blot. To determine the level of protein synthesised, transfected cell lysates were then submitted to Western blot. The nonsecreted form of the recombinant GroEL produced by the pCMV-link construct was detected in much greater amount than the secreted form of the protein produced by the pCMV-tPA construct. After immunisation, a strong anti-GroEL IgG response was detected in mice vaccinated by i.m. injection or gene gun only when the pCMV-link/ GroEL plasmid was used. Regarding the pattern of immune response induced, i.m. needle injection raised a predominantly Th1 response with mostly IgG2a-speci®c antiGroEL and high levels of IFN-ã produced by splenic T cells. Gene gun immunisation induced a Th0 type of immune response in mice characterised by a high IgG1/IgG2a ratio, and IL-4 and interferon (IFN)-ã production. Even though a distinct pattern of immune response was generated depending upon the immunisation route used, neither method engendered a signi®cant level of protection with the GroEL DNA vaccine.

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“…Keywords: gene therapy; regeneration; ␤-galactosidase; muscle; plasmid; inflammation Skeletal muscle has the ability to take up and express naked plasmid DNA following intramuscular injection 1,2 and hence is an attractive platform for (1) providing a systemic source for recombinant therapeutic proteins; 3,4 and (2) as a means of genetic vaccination against either bacteria and viruses, [5][6][7] or tumour cells. [8][9][10] However, long-term expression of transgenes encoded in the plasmid DNA can be limited by the immune responses (cellular, humoral and innate) evoked during the processes of gene uptake and expression in skeletal muscle fibres.…”

mentioning

confidence: 99%

Inflammatory responses following direct injection of plasmid DNA into skeletal muscle

et al. 1998

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Transfer of genes by injection of plasmid DNA into skeletal generated widespread inflammation of injected muscle, muscle has a wide variety of applications ranging from with mononuclear infiltrate, comprised largely of macrotreatment of neuromuscular disorders to genetic vacciphages and with both CD4 + and CD8 + T lymphocytes, nation. We examined each component involved in the present. Such inflammation may hamper clinical appliintramuscular injection of plasmid DNA in terms of the cation of this technology and may encourage undesirable induction of inflammatory responses. The insertion of a immune responses in gene therapy trials. Inflammation needle and the injection of a relatively large volume of was not greatly reduced by CD4-or CD8-depleting antisaline caused very little muscle damage except in rare bodies, suggesting this initial inflammation did not involve cases. In contrast, barium chloride-induced regeneration of T cells, but methylation of plasmid DNA before injection muscle, injection of lipopolysaccharide, plasmid backbone substantially lessened the inflammatory response and or plasmid expressing a neo-antigen (␤-galactosidase) all resulted in longer term expression of the transgene.Keywords: gene therapy; regeneration; ␤-galactosidase; muscle; plasmid; inflammation Skeletal muscle has the ability to take up and express naked plasmid DNA following intramuscular injection 1,2 and hence is an attractive platform for (1) providing a systemic source for recombinant therapeutic proteins; 3,4 and (2) as a means of genetic vaccination against either bacteria and viruses, 5-7 or tumour cells. [8][9][10] However, long-term expression of transgenes encoded in the plasmid DNA can be limited by the immune responses (cellular, humoral and innate) evoked during the processes of gene uptake and expression in skeletal muscle fibres. 11-15 These responses, while necessary and desirable for genetic vaccination, can seriously limit the use of direct plasmid injection for gene therapy. Immune responses also play a significant role in determining the success of virus-based gene transfer. [16][17][18][19][20][21][22] In order to start to dissect the relative roles of the responses to vector and transgene, we have concentrated on gene transfer by direct injection of plasmid DNA. This system does not involve injection of any exogenous protein component, allowing the characteristics of the antigen-specific response to be analysed separately. However, plasmid DNA is prepared in E. coli which results both in contamination with lipopolysaccharide (LPS, endotoxin) and the presence of unmethylated CpG motifs. LPS is a known stimulator of immune responses and is frequently used for in vitro stimulation of lymphocyte populations. [23][24][25] Unmethylated CpG motifs are comparatively rare in eukaryotic genomes 26

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Characterization of humoral immune responses induced by an influenza hemagglutinin DNA vaccine

Cited by 134 publications

References 27 publications

HER2 peptide-specific CD8+ T cells are proportionally detectable long after multiple DNA vaccinations

HER2 peptide-specific CD8+ T cells are proportionally detectable long after multiple DNA vaccinations

Induction of a Th1-type of immune response but not protective immunity by intramuscular DNA immunisation with Brucella abortus GroEL heat-shock gene

Inflammatory responses following direct injection of plasmid DNA into skeletal muscle

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