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Plos One : Mannosylated Mucin-type Immunoglobulin Fusion Proteins Enhance Antigen-specific Antibody and T Lymphocyte Responses, Volume 7

By Rodrigues, Mauricio Martins

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Book Id: WPLBN0003940387
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos One : Mannosylated Mucin-type Immunoglobulin Fusion Proteins Enhance Antigen-specific Antibody and T Lymphocyte Responses, Volume 7  
Author: Rodrigues, Mauricio Martins
Volume: Volume 7
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection (Contemporary)
Historic
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Publisher: Plos

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Rodrigues, M. M. (n.d.). Plos One : Mannosylated Mucin-type Immunoglobulin Fusion Proteins Enhance Antigen-specific Antibody and T Lymphocyte Responses, Volume 7. Retrieved from http://netlibrary.net/


Description
Description : 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-c, IL-2, IL-4 and IL-5 ELISpot assays. Immunizations with the OVA 2 mannosylated PSGL-1/ mIgG2b conjugate, especially when combined with the AbISCOH-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 AbISCOH-100. Also non-covalent mixing of mannosylated PSGL-1/mIgG2b, OVA and AbISCOH-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.

 

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