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Mannosylated mucin-...
Mannosylated mucin-type immunoglobulin fusion proteins enhance antigen-specific antibody and T lymphocyte responses
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- Ahlén, Gustaf (author)
- Recopharma AB, Stockholm, Sweden
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- Strindelius, Lena (author)
- Recopharma AB, Stockholm, Sweden
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- Johansson, Tomas (author)
- Recopharma AB, Stockholm, Sweden
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- Nilsson, Anki (author)
- Recopharma AB, Stockholm, Sweden
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- Chatzissavidou, Nathalie (author)
- Recopharma AB, Stockholm, Sweden
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- Sjöblom, Magnus (author)
- Luleå tekniska universitet,Industriell miljö- och processteknik
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- Rova, Ulrika (author)
- Luleå tekniska universitet,Industriell miljö- och processteknik
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- Holgersson, Jan (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine,Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, Gothenburg, Sweden
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(creator_code:org_t)
- 2012-10-12
- 2012
- English.
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://gup.ub.gu.se...
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Abstract
Subject headings
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- Targeting antigens to antigen-presenting cells (APC) improve their immunogenicity and capacity to induce Th1 responses and cytotoxic T lymphocytes (CTL). We have generated a mucin-type immunoglobulin fusion protein (PSGL-1/mIgG2b), which upon expression in the yeast Pichia pastoris became multivalently substituted with O-linked oligomannose structures and bound the macrophage mannose receptor (MMR) and dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) with high affinity in vitro. Here, its effects on the humoral and cellular anti-ovalbumin (OVA) responses in C57BL/6 mice are presented.OVA antibody class and subclass responses were determined by ELISA, the generation of anti-OVA CTLs was assessed in 51Cr release assays using in vitro-stimulated immune spleen cells from the different groups of mice as effector cells and OVA peptide-fed RMA-S cells as targets, and evaluation of the type of Th cell response was done by IFN-γ, IL-2, IL-4 and IL-5 ELISpot assays.Immunizations with the OVA − mannosylated PSGL-1/mIgG2b conjugate, especially when combined with the AbISCO®-100 adjuvant, lead to faster, stronger and broader (with regard to IgG subclass) OVA IgG responses, a stronger OVA-specific CTL response and stronger Th1 and Th2 responses than if OVA was used alone or together with AbISCO®-100. Also non-covalent mixing of mannosylated PSGL-1/mIgG2b, OVA and AbISCO®-100 lead to relatively stronger humoral and cellular responses. The O-glycan oligomannoses were necessary because PSGL-1/mIgG2b with mono- and disialyl core 1 structures did not have this effect.Mannosylated mucin-type fusion proteins can be used as versatile APC-targeting molecules for vaccines and as such enhance both humoral and cellular immune responses.
Subject headings
- TEKNIK OCH TEKNOLOGIER -- Industriell bioteknik -- Bioprocessteknik (hsv//swe)
- ENGINEERING AND TECHNOLOGY -- Industrial Biotechnology -- Bioprocess Technology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- Biokemisk processteknik
- Biochemical Process Engineering
Publication and Content Type
- ref (subject category)
- art (subject category)
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