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Improved cellular and humoral immune responses in vivo following targeting of HIV Gag to dendritic cells within human anti-human DEC205 monoclonal antibody

Authors
 Cheolho Cheong  ;  Jae-Hoon Choi  ;  Laura Vitale  ;  Li-Zhen He  ;  Christine Trumpfheller  ;  Leonia Bozzacco  ;  Yoonkyung Do  ;  Godwin Nchinda  ;  Sung Ho Park  ;  Durga Bhavani Dandamudi  ;  Elina Shrestha  ;  Maggi Pack  ;  Han-Woong Lee  ;  Tibor Keler  ;  Ralph M. Steinman  ;  Chae Gyu Park 
Citation
 BLOOD, Vol.116(19) : 3828-3838, 2010 
Journal Title
 BLOOD 
ISSN
 0006-4971 
Issue Date
2010
MeSH
AIDS Vaccines/genetics ; AIDS Vaccines/immunology ; Animals ; Antibodies, Monoclonal ; Antigens, CD/genetics ; Antigens, CD/immunology* ; Base Sequence ; Cross-Priming ; DNA Primers/genetics ; Dendritic Cells/immunology* ; Dendritic Cells/virology* ; HIV Core Protein p24/genetics ; HIV Core Protein p24/immunology* ; HIV-1/genetics ; HIV-1/immunology* ; Humans ; Immunity, Cellular ; Immunity, Humoral ; Lectins, C-Type/genetics ; Lectins, C-Type/immunology* ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Minor Histocompatibility Antigens ; Receptors, Cell Surface/genetics ; Receptors, Cell Surface/immunology* ; Recombinant Proteins/genetics ; Recombinant Proteins/immunology ; Simian Immunodeficiency Virus/genetics ; Simian Immunodeficiency Virus/immunology ; Vaccines, Subunit/genetics ; Vaccines, Subunit/immunology
Abstract
Protein vaccines for T-cell immunity are not being prioritized because of poor immunogenicity. To overcome this hurdle, proteins are being targeted to maturing dendritic cells (DCs) within monoclonal antibodies (mAbs) to DC receptors. To extend the concept to humans, we immunized human immunoglobulin-expressing mice with human DEC205 (hDEC205) extracellular domain. 3D6 and 3G9 mAbs were selected for high-affinity binding to hDEC205. In addition, CD11c promoter hDEC205 transgenic mice were generated, and 3G9 was selectively targeted to DCs in these animals. When mAb heavy chain was engineered to express HIV Gag p24, the fusion mAb induced interferon-γ- and interleukin-2-producing CD4(+) T cells in hDEC205 transgenic mice, if polynocinic polycytidylic acid was coadministered as an adjuvant. The T-cell response was broad, recognizing at least 3 Gag peptides, and high titers of anti-human immunoglobulin G antibody were made. Anti-hDEC205 also improved the cross-presentation of Gag to primed CD8(+) T cells from HIV-infected individuals. In all tests, 3D6 and 3G9 targeting greatly enhanced immunization relative to nonbinding control mAb. These results provide preclinical evidence that in vivo hDEC205 targeting increases the efficiency with which proteins elicit specific immunity, setting the stage for proof-of-concept studies of these new protein vaccines in human subjects
Files in This Item:
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DOI
10.1182/blood-2010-06-288068
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Park, Chae Gyu(박채규) ORCID logo https://orcid.org/0000-0003-1906-1308
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/103269
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