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Divergence of Primary Cognate B- and T-Cell Proliferative Responses to Subcutaneous and Intravenous Immunization with Virus-Like Particles

A major advantage of virus-like particle (VLP) vaccines against HIV is their structural identity to wild-type viruses, ensuring that antigen-specific B-cells encounter the envelope protein in its natural conformation. For the induction of affinity-matured antibodies, the B-cells must also obtain hel...

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Autores principales: Temchura, Vladimir, Kalinin, Svetlana, Nabi, Ghulam, Tippler, Bettina, Niezold, Thomas, Überla, Klaus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147698/
https://www.ncbi.nlm.nih.gov/pubmed/25153345
http://dx.doi.org/10.3390/v6083334
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author Temchura, Vladimir
Kalinin, Svetlana
Nabi, Ghulam
Tippler, Bettina
Niezold, Thomas
Überla, Klaus
author_facet Temchura, Vladimir
Kalinin, Svetlana
Nabi, Ghulam
Tippler, Bettina
Niezold, Thomas
Überla, Klaus
author_sort Temchura, Vladimir
collection PubMed
description A major advantage of virus-like particle (VLP) vaccines against HIV is their structural identity to wild-type viruses, ensuring that antigen-specific B-cells encounter the envelope protein in its natural conformation. For the induction of affinity-matured antibodies, the B-cells must also obtain help from T-cells that are restricted by linear epitopes. Using B- and T-cell transgenic mouse models, we compared the efficacy of modified HIV-VLPs delivered by subcutaneous and intravenous immunization to stimulate primary B- and T-cell proliferative responses in different lymphoid organs. VLPs containing an influenza virus hemagglutinin epitope within the HIV-Gag protein induced comparable primary cognate T-cell proliferative responses in the draining lymph node and the spleen, irrespective of the delivery route. In contrast, after subcutaneous immunization with HIV-Gag VLPs containing hen egg lysozyme (HEL) on their surface, the proliferative response of transgenic HEL-specific B-cells was restricted to the draining lymph nodes, while intravenous VLP immunization primarily induced a B-cell proliferative response in the spleen. In vitro co-culture experiments further revealed that the presentation of VLP-associated surface antigens by dendritic cells to cognate B-cells is inefficient. This is consistent with a direct triggering of the B-cell proliferative response by the VLPs and suggests that HIV VLPs may indeed be suitable to directly promote the expansion of B-cells specific for conformational epitopes that are unique to functionally-active Env spikes on the virion. Further investigations are warranted to explore potential differences in the quality and protective potency of HIV-specific antibody responses induced by the two routes.
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spelling pubmed-41476982014-08-28 Divergence of Primary Cognate B- and T-Cell Proliferative Responses to Subcutaneous and Intravenous Immunization with Virus-Like Particles Temchura, Vladimir Kalinin, Svetlana Nabi, Ghulam Tippler, Bettina Niezold, Thomas Überla, Klaus Viruses Article A major advantage of virus-like particle (VLP) vaccines against HIV is their structural identity to wild-type viruses, ensuring that antigen-specific B-cells encounter the envelope protein in its natural conformation. For the induction of affinity-matured antibodies, the B-cells must also obtain help from T-cells that are restricted by linear epitopes. Using B- and T-cell transgenic mouse models, we compared the efficacy of modified HIV-VLPs delivered by subcutaneous and intravenous immunization to stimulate primary B- and T-cell proliferative responses in different lymphoid organs. VLPs containing an influenza virus hemagglutinin epitope within the HIV-Gag protein induced comparable primary cognate T-cell proliferative responses in the draining lymph node and the spleen, irrespective of the delivery route. In contrast, after subcutaneous immunization with HIV-Gag VLPs containing hen egg lysozyme (HEL) on their surface, the proliferative response of transgenic HEL-specific B-cells was restricted to the draining lymph nodes, while intravenous VLP immunization primarily induced a B-cell proliferative response in the spleen. In vitro co-culture experiments further revealed that the presentation of VLP-associated surface antigens by dendritic cells to cognate B-cells is inefficient. This is consistent with a direct triggering of the B-cell proliferative response by the VLPs and suggests that HIV VLPs may indeed be suitable to directly promote the expansion of B-cells specific for conformational epitopes that are unique to functionally-active Env spikes on the virion. Further investigations are warranted to explore potential differences in the quality and protective potency of HIV-specific antibody responses induced by the two routes. MDPI 2014-08-22 /pmc/articles/PMC4147698/ /pubmed/25153345 http://dx.doi.org/10.3390/v6083334 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Temchura, Vladimir
Kalinin, Svetlana
Nabi, Ghulam
Tippler, Bettina
Niezold, Thomas
Überla, Klaus
Divergence of Primary Cognate B- and T-Cell Proliferative Responses to Subcutaneous and Intravenous Immunization with Virus-Like Particles
title Divergence of Primary Cognate B- and T-Cell Proliferative Responses to Subcutaneous and Intravenous Immunization with Virus-Like Particles
title_full Divergence of Primary Cognate B- and T-Cell Proliferative Responses to Subcutaneous and Intravenous Immunization with Virus-Like Particles
title_fullStr Divergence of Primary Cognate B- and T-Cell Proliferative Responses to Subcutaneous and Intravenous Immunization with Virus-Like Particles
title_full_unstemmed Divergence of Primary Cognate B- and T-Cell Proliferative Responses to Subcutaneous and Intravenous Immunization with Virus-Like Particles
title_short Divergence of Primary Cognate B- and T-Cell Proliferative Responses to Subcutaneous and Intravenous Immunization with Virus-Like Particles
title_sort divergence of primary cognate b- and t-cell proliferative responses to subcutaneous and intravenous immunization with virus-like particles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4147698/
https://www.ncbi.nlm.nih.gov/pubmed/25153345
http://dx.doi.org/10.3390/v6083334
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