Anti-idiotypic antibodies induced by genetic immunisation are directed exclusively against combined VL/VH determinants

Benvenuti, Federica; Or, Burrone

doi:10.1038/sj.gt.3301546

Cited by 19 publications

(16 citation statements)

References 30 publications

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“…Groups of six female BALB/c mice of 5-6 weeks old (Harlan) were immunized three times at 15 day intervals (days 1, 15 and 30) by biolistic delivery of 1 mm gold particles coated with 1 mg of DNA using Gene Gun technology (Bio-Rad) (Benvenuti & Burrone, 2001;Cesco-Gaspere et al, 2005); blood samples were collected at days 45 and 60 by submandibular puncture. All animal procedures were performed in compliance to laws and policies established in the legislation (D. L.vo 26/2014 of the Italian Government, protocol DGSAF0024706).…”

Section: Methodsmentioning

confidence: 99%

Secretion of dengue virus envelope protein ectodomain from mammalian cells is dependent on domain II serotype and affects the immune response upon DNA vaccination

Slon-Campos

Poggianella

Marchese

et al. 2015

Journal of General Virology

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Dengue virus (DENV) is currently among the most important human pathogens and affects millions of people throughout the tropical and subtropical regions of the world. Although it has been a World Health Organization priority for several years, there is still no efficient vaccine available to prevent infection. The envelope glycoprotein (E), exposed on the surface on infective viral particles, is the main target of neutralizing antibodies. For this reason it has been used as the antigen of choice for vaccine development efforts. Here we show a detailed analysis of factors involved in the expression, secretion and folding of E ectodomain from all four DENV serotypes in mammalian cells, and how this affects their ability to induce neutralizing antibody responses in DNA-vaccinated mice. Proper folding of E domain II (DII) is essential for efficient E ectodomain secretion, with DIII playing a significant role in stabilizing soluble dimers. We also show that the level of protein secreted from transfected cells determines the strength and efficiency of antibody responses in the context of DNA vaccination and should be considered a pivotal feature for the development of E-based DNA vaccines against DENV.

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Section: Methodsmentioning

confidence: 99%

Secretion of dengue virus envelope protein ectodomain from mammalian cells is dependent on domain II serotype and affects the immune response upon DNA vaccination

Slon-Campos

Poggianella

Marchese

et al. 2015

Journal of General Virology

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“…BALB/c mice were vaccinated three times at 2-wk intervals with 1 g of plasmid by gene-gun technique (20,21). Fifteen days after the last boost, blood was collected via retro-orbital puncture.…”

Section: Mice and Guinea Pig Immunization And Sera Analysismentioning

confidence: 99%

“…1). These molecules are efficiently folded and expressed as dimers on the surface of trans- (9,20,21). In addition, normal signaling of A20 expressing mSIPs of and ␥1 isotypes ( L -mSIP, Sh -mSIP, and ␥1-mSIP) was confirmed by analyzing their ability to promote intracellular Ca 2ϩ mobilization upon cross-linking.…”

Section: Immunoreceptors and Ca 2ϩ Mobilizationmentioning

confidence: 99%

The Extracellular Membrane-Proximal Domain of Human Membrane IgE Controls Apoptotic Signaling of the B Cell Receptor in the Mature B Cell Line A20

Poggianella

Bestagno

Burrone

2006

The Journal of Immunology

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Ag engagement of BCR in mature B cells can deliver specific signals, which decide cell survival or cell death. Circulating membrane IgE+ (mIgE+) cells are found in extremely low numbers. We hypothesized that engagement of an εBCR in a mature isotype-switched B cell could induce apoptosis. We studied the role of the extracellular membrane-proximal domain (EMPD) of human mIgE upon BCR engagement with anti-Id Abs. Using mutants lacking the EMPD, we show that this domain is involved in controlling Ca2+ mobilization in immunoreceptors of both γ and ε isotypes, as well as apoptosis in signaling originated only from the εBCR. We mapped to the εCH4 ectodomain the region responsible for apoptosis in EMPD-deleted receptors. Ca2+ mobilization was not related to apoptotic signaling. This apoptotic pathway was caspase independent, involved ERK1/2 phosphorylation and was partially rescued by CD40 costimulation. We therefore conclude that the EMPD of human mIgE is a key control element of apoptotic signaling delivered through engagement of εBCR within the context of a mature B cell.

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“…Within variable regions, the CDR3s are the sites of highest variability and vaccines including only this minimal antigenic domain were proved to induce antibody responses [Rinaldi 2001, Lim 2001. However, to induce conformational antibodies able to bind to the native immunoglobulin on the surface of malignant cells vaccines must include the two variable regions [Benvenuti, 2001]. A common approach to maintain the idiotype in a simplified conformation is the assembly into single chain Fv (scFv) molecules that contain only VL and VH linked by a short flexible linker.…”

Section: Anti-idiotypic Genetic Vaccinesmentioning

confidence: 99%

“…By using a strategy that allows to analyse the binding of anti-Id antibodies to properly folded idiotypes displayed on the surface of transfected cells, we showed that anti-Id antibodies induced by scFv DNA vaccination are directed exclusively to epitopes arising from the VL/VH association, thus highly specific [Benvenuti 2001]. Interestingly, the same immunogen delivered as scFv protein induced antibodies directed also against V region (VL and VH) specific determinants (Fig.…”

Section: Mechanism Of Rejection Of Lymphoma Cells By Anti-id Vaccinationmentioning

confidence: 99%

Genetic Vaccination for the Immunotherapy of B-Cell Malignancies

Benvenuti

Or²

2002

CGT

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Vaccination protocols based on targeting of the idiotype expressed on malignant B cells have so far provided encouraging results in clinical trials. The essential requirement to induce an immune response is the inclusion of carriers to overcome T-cell tolerance. Chemical cross-linking of idiotypic protein is so far the method of choice to induce protective responses in human studies. Meanwhile, a flurry of alternative strategies to simplify vaccine production is being tested in murine model. Thanks to the advance in antibody engineering the two relevant antigenic domains of the lymphoma immunoglobulin can be assembled into an appropriate format, genetically linked to molecules that act as immunological adjuvants and directly delivered as plasmid DNA. Upon immunization, rejection of tumor cells may depend on cellular or humoral mechanisms, whose relative importance has not been entirely estimated. We have recently analyzed the specificity of anti-idiotypic antibodies induced by DNA vaccination and characterised the elements contributing to optimal anti-idiotypic responses.

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Anti-idiotypic antibodies induced by genetic immunisation are directed exclusively against combined VL/VH determinants

Cited by 19 publications

References 30 publications

Secretion of dengue virus envelope protein ectodomain from mammalian cells is dependent on domain II serotype and affects the immune response upon DNA vaccination

Secretion of dengue virus envelope protein ectodomain from mammalian cells is dependent on domain II serotype and affects the immune response upon DNA vaccination

The Extracellular Membrane-Proximal Domain of Human Membrane IgE Controls Apoptotic Signaling of the B Cell Receptor in the Mature B Cell Line A20

Genetic Vaccination for the Immunotherapy of B-Cell Malignancies

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