Intensified and protective CD4+ T cell immunity in mice with anti–dendritic cell HIV gag fusion antibody vaccine

Current human immunodeficiency virus (HIV) vaccine approaches emphasize prime boost strategies comprising multiple doses of DNA vaccine and recombinant viral vectors. We are developing a protein-based approach that directly harnesses principles for generating T cell immunity. Vaccine is delivered to...

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Main Authors:	Trumpfheller, Christine, Finke, Jennifer S., López, Carolina B., Moran, Thomas M., Moltedo, Bruno, Soares, Helena, Huang, Yaoxing, Schlesinger, Sarah J., Park, Chae Gyu, Nussenzweig, Michel C., Granelli-Piperno, Angela, Steinman, Ralph M.
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2006
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118242/

id	pubmed-2118242
recordtype	oai_dc
spelling	pubmed-21182422007-12-13 Intensified and protective CD4+ T cell immunity in mice with anti–dendritic cell HIV gag fusion antibody vaccine Trumpfheller, Christine Finke, Jennifer S. López, Carolina B. Moran, Thomas M. Moltedo, Bruno Soares, Helena Huang, Yaoxing Schlesinger, Sarah J. Park, Chae Gyu Nussenzweig, Michel C. Granelli-Piperno, Angela Steinman, Ralph M. Articles Current human immunodeficiency virus (HIV) vaccine approaches emphasize prime boost strategies comprising multiple doses of DNA vaccine and recombinant viral vectors. We are developing a protein-based approach that directly harnesses principles for generating T cell immunity. Vaccine is delivered to maturing dendritic cells in lymphoid tissue by engineering protein antigen into an antibody to DEC-205, a receptor for antigen presentation. Here we characterize the CD4+ T cell immune response to HIV gag and compare efficacy with other vaccine strategies in a single dose. DEC-205–targeted HIV gag p24 or p41 induces stronger CD4+ T cell immunity relative to high doses of gag protein, HIV gag plasmid DNA, or recombinant adenovirus-gag. High frequencies of interferon (IFN)-γ– and interleukin 2–producing CD4+ T cells are elicited, including double cytokine-producing cells. In addition, the response is broad because the primed mice respond to an array of peptides in different major histocompatibility complex haplotypes. Long-lived T cell memory is observed. After subcutaneous vaccination, CD4+ and IFN-γ–dependent protection develops to a challenge with recombinant vaccinia-gag virus at a mucosal surface, the airway. We suggest that a DEC-targeted vaccine, in part because of an unusually strong and protective CD4+ T cell response, will improve vaccine efficacy as a stand-alone approach or with other modalities. The Rockefeller University Press 2006-03-20 /pmc/articles/PMC2118242/ /pubmed/16505141 http://dx.doi.org/10.1084/jem.20052005 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Trumpfheller, Christine Finke, Jennifer S. López, Carolina B. Moran, Thomas M. Moltedo, Bruno Soares, Helena Huang, Yaoxing Schlesinger, Sarah J. Park, Chae Gyu Nussenzweig, Michel C. Granelli-Piperno, Angela Steinman, Ralph M.
spellingShingle	Trumpfheller, Christine Finke, Jennifer S. López, Carolina B. Moran, Thomas M. Moltedo, Bruno Soares, Helena Huang, Yaoxing Schlesinger, Sarah J. Park, Chae Gyu Nussenzweig, Michel C. Granelli-Piperno, Angela Steinman, Ralph M. Intensified and protective CD4+ T cell immunity in mice with anti–dendritic cell HIV gag fusion antibody vaccine
author_facet	Trumpfheller, Christine Finke, Jennifer S. López, Carolina B. Moran, Thomas M. Moltedo, Bruno Soares, Helena Huang, Yaoxing Schlesinger, Sarah J. Park, Chae Gyu Nussenzweig, Michel C. Granelli-Piperno, Angela Steinman, Ralph M.
author_sort	Trumpfheller, Christine
title	Intensified and protective CD4+ T cell immunity in mice with anti–dendritic cell HIV gag fusion antibody vaccine
title_short	Intensified and protective CD4+ T cell immunity in mice with anti–dendritic cell HIV gag fusion antibody vaccine
title_full	Intensified and protective CD4+ T cell immunity in mice with anti–dendritic cell HIV gag fusion antibody vaccine
title_fullStr	Intensified and protective CD4+ T cell immunity in mice with anti–dendritic cell HIV gag fusion antibody vaccine
title_full_unstemmed	Intensified and protective CD4+ T cell immunity in mice with anti–dendritic cell HIV gag fusion antibody vaccine
title_sort	intensified and protective cd4+ t cell immunity in mice with anti–dendritic cell hiv gag fusion antibody vaccine
description	Current human immunodeficiency virus (HIV) vaccine approaches emphasize prime boost strategies comprising multiple doses of DNA vaccine and recombinant viral vectors. We are developing a protein-based approach that directly harnesses principles for generating T cell immunity. Vaccine is delivered to maturing dendritic cells in lymphoid tissue by engineering protein antigen into an antibody to DEC-205, a receptor for antigen presentation. Here we characterize the CD4+ T cell immune response to HIV gag and compare efficacy with other vaccine strategies in a single dose. DEC-205–targeted HIV gag p24 or p41 induces stronger CD4+ T cell immunity relative to high doses of gag protein, HIV gag plasmid DNA, or recombinant adenovirus-gag. High frequencies of interferon (IFN)-γ– and interleukin 2–producing CD4+ T cells are elicited, including double cytokine-producing cells. In addition, the response is broad because the primed mice respond to an array of peptides in different major histocompatibility complex haplotypes. Long-lived T cell memory is observed. After subcutaneous vaccination, CD4+ and IFN-γ–dependent protection develops to a challenge with recombinant vaccinia-gag virus at a mucosal surface, the airway. We suggest that a DEC-targeted vaccine, in part because of an unusually strong and protective CD4+ T cell response, will improve vaccine efficacy as a stand-alone approach or with other modalities.
publisher	The Rockefeller University Press
publishDate	2006
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118242/
_version_	1611414644640972800

Intensified and protective CD4+ T cell immunity in mice with anti–dendritic cell HIV gag fusion antibody vaccine

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