Heterologous and Homologous Protection Against Influenza A by DNA Vaccination: Optimization of DNA Vectors

Montgomery, Donna L.; Shiver, John W.; Leander, Karen; Perry, Helen C.; Friedman, Arthur; Martinez, Douglas; Ulmer, Jeffrey B.; Donnelly, John; Liu, Margaret A.

doi:10.1089/dna.1993.12.777

Cited by 250 publications

(129 citation statements)

References 19 publications

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“…An increase in the antibody response against this influenza antigen is highest upon natural infection, moderate after vaccination with MLV and least effective after immunization with inactivated preparations [26]. However, the induction of cytotoxic T cell responses and memory CD8+ cells are considered important for protection as well, and, in fact, the first successful DNA vaccination against a virus was shown with the influenza virus nucleoprotein in mice [27]. Here we show that following inoculation with our MLV rH_EIV, H3-specific immune responses were induced in both mice and dogs.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the vaccine might also benefit from insertion of other important influenza proteins like e.g. the nucleoprotein [27]. Although such a vectored combination vaccine would first need to be fully re-characterized for proper growth in vitro and expression, we do not foresee major problems since EHV-1 is known to accommodate large amounts of foreign DNA [14].…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of a vectored equine herpesvirus type 1 (EHV-1) vaccine expressing H3 haemagglutinin in the protection of dogs against canine influenza

Rosas

Walle

Metzger

et al. 2008

Vaccine

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In 2004, canine influenza virus (CIV) was identified as a respiratory pathogen of dogs for the first time and is closely related to H3N8 equine influenza virus (EIV). We generated a recombinant vectored vaccine that expresses H3 of a recent isolate of EIV using equine herpesvirus type 1 (EHV-1) as the delivery vehicle. This EHV-1 vectored vaccine exhibited robust and stable EIV H3 expression and induced a strong influenza virus-specific response in both mice and dogs upon intranasal or subcutaneous administration. Furthermore, upon challenge with the recent CIV isolate A/canine/PA/ 10915-07, protection of vaccinated dogs could be demonstrated by a significant reduction in clinical sings, and, more importantly, by a significant reduction in virus shedding. We concluded that the EHV-1/H3 recombinant vector can be a valuable alternative for protection of dogs against clinical disease induced by CIV and can significantly reduce spread.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluation of a vectored equine herpesvirus type 1 (EHV-1) vaccine expressing H3 haemagglutinin in the protection of dogs against canine influenza

Rosas

Walle

Metzger

et al. 2008

Vaccine

View full text Add to dashboard Cite

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“…CEA cDNA from plasmid pCI/CEA 34 was cloned into the EcoRI site of plasmid pVIJnsA. 33 The CEA cDNAs were placed under the control of the human cytomegalovirus (CMV)/ intron A promoter plus the bovine growth hormone (BGH) termination signal.…”

Section: Figure 2 -Comparison Of Different Immunization Regimensmentioning

confidence: 99%

“…33 The construct was named pVIJ/CEA. In addition, an adenovirus type 5 vector was constructed carrying the CEA cDNA (Ad-CEA).…”

Section: Construction Of Human Cea Expression Vectorsmentioning

confidence: 99%

Efficient induction of T‐cell responses to carcinoembryonic antigen by a heterologous prime‐boost regimen using DNA and adenovirus vectors carrying a codon usage optimized cDNA

Mennuni

Calvaruso

Facciabene

et al. 2005

Intl Journal of Cancer

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The immunogenic properties of plasmid DNA and recombinant adenovirus (Ad) encoding the carcinoembryonic antigen (CEA) were examined in mice by measuring both the amplitude and type of immune response, and the immunogenicity of codon usage optimized cDNA encoding CEA (CEAopt) was assessed both in C57Bl/6 and CEA transgenic mice. Vectors were injected into quadriceps muscle either alone or in combination, and plasmid DNA was electroporated to enhance gene expression efficiency and immunogenicity. Injection of plasmid pVIJ/CEA followed by Ad-CEA boost elicited the highest amplitude of both CD4 1 and CD8 1 T-cell response to the target antigen, measured by both IFNc-ELIspot assay and intracellular staining. Vectors carrying cDNA of CEAopt expressed a greater amount of the CEA protein than their wild-type counterparts, and this enhanced expression was associated with greater immunogenicity. Both CD4 1 and CD8 1 T-cell epitopes were mapped in the C-terminal portion of the protein. In CEA transgenic mice, only immunization based on repeated injections of pVIJ/ CEAopt followed by Ad-CEAopt was able to elicit a CEA-specific CD8 1 T-cell response, whereas the wild-type vectors did not break tolerance to this target antigen. MC38-CEA tumor cells injected s.c. in CEA transgenic mice vaccinated with CEAopt vectors exhibited delayed growth kinetics. These studies demonstrate that this type of genetic vaccine is highly immunogenic and can break tolerance to CEA tumor antigen in CEA transgenic mice. ' 2005 Wiley-Liss, Inc.Key words: CEA; DNA electroporation; adenovirus Despite improvements in prevention, early detection and treatment, the possibility of curing many cancer patients remains elusive. Thus, cancer continues to be a largely unmet medical need for which more efficient therapeutic strategies must be developed. 1 Particular attention has been given to active specific immunotherapy of cancer, whereby patients are immunized against antigens presented by tumor cells. In fact, experimental and clinical evidence have demonstrated the critical role played by the cellular and humoral responses in controlling tumor growth and metastasis. 2 Many of these therapies are specifically targeted to tumorassociated antigens among which carcinoembryonic antigen (CEA) is a frequent example due to its ectopic and deregulated expression in a large percentage of adenocarcinomas. 3 Human CEA is the prototypic member of the human CEA family, a group of highly glycosylated homotypic/heterotypic cell surface intracellular adhesion molecules, and part of the immunoglobulin gene superfamily. CEA is widely used as human tumor marker, is expressed mostly in the gastrointestinal tract and is overexpressed in many human cancers, including epithelial tumors originating from the gastrointestinal tract, lung, thyroid, breast, prostate, cervix and ovaries. 4 CEA has been the focus of extensive preclinical and clinical investigation aimed at developing a CEA-specific vaccine with a therapeutic impact on tumor progression. 5 In this context, genetic vacc...

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“…To generate a plasmid vaccine, hEp-CAM, mEp-CAM and rhEp-CAM were subcloned into the pV1J expression vector [29]. Ad vectors were constructed as described [30].…”

Section: Antigens and Vaccine Vectorsmentioning

confidence: 99%

Genetic vaccines against Ep‐CAM break tolerance to self in a limited subset of subjects: Initial identification of predictive biomarkers

et al. 2006

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The epithelial cell adhesion molecule, Ep-CAM, has been historically considered a target of passive immunotherapy using monoclonal antibodies, and more recently, of a first Pox-vector-based cancer vaccine Phase I trial in colorectal cancer patients. To shed further light on the use of this antigen, we isolated the mouse and rhesus homologues of human Ep-CAM and explored different genetic vaccination modalities based on the use of adenoviral vectors as well as DNA electroporation (DNA-EP). Immune responses to Ep-CAM were measured by IFN-c ELISPOT and intracellular staining assays using overlapping sets of peptides covering the entire coding regions. We found the most powerful vaccination regimen to be constituted by DNA-EP-prime/Adeno-boost mixedmodality protocols. Vaccination in rhesus macaques resulted in breakage of immunological tolerance in a minority of cases. Similarly, a low frequency of responders was observed with the mouse Ep-CAM vaccine in outbred CD1 mice. When immunized CD1 mice were analyzed for MHC haplotype and TCR expression levels, we observed that immune responders all had the same q/q MHC class I haplotype and showed higher expression levels of the TCRVb4 and TCRVb8 T cell receptors. Our results underscore the current limitations in our capacity to induce efficient cancer vaccines against self antigens like Ep-CAM, but also represent a first effort to identify predictive biomarkers of response.See accompanying commentary: http://dx

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Heterologous and Homologous Protection Against Influenza A by DNA Vaccination: Optimization of DNA Vectors

Cited by 250 publications

References 19 publications

Evaluation of a vectored equine herpesvirus type 1 (EHV-1) vaccine expressing H3 haemagglutinin in the protection of dogs against canine influenza

Evaluation of a vectored equine herpesvirus type 1 (EHV-1) vaccine expressing H3 haemagglutinin in the protection of dogs against canine influenza

Efficient induction of T‐cell responses to carcinoembryonic antigen by a heterologous prime‐boost regimen using DNA and adenovirus vectors carrying a codon usage optimized cDNA

Genetic vaccines against Ep‐CAM break tolerance to self in a limited subset of subjects: Initial identification of predictive biomarkers

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