Next Article in Journal
Assembly and Maturation of a T = 4 Quasi-Equivalent Virus Is Guided by Electrostatic and Mechanical Forces
Next Article in Special Issue
HIV-1 Env-Specific Memory and Germinal Center B Cells in C57BL/6 Mice
Previous Article in Journal
Immunogenetics of Small Ruminant Lentiviral Infections
Previous Article in Special Issue
Mechanisms of HIV Protein Degradation into Epitopes: Implications for Vaccine Design
Viruses 2014, 6(8), 3334-3347; doi:10.3390/v6083334
Article

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

* ,
,
,
,
 and
Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, D-44780, Germany
* Author to whom correspondence should be addressed.
Received: 28 May 2014 / Revised: 15 August 2014 / Accepted: 18 August 2014 / Published: 22 August 2014
(This article belongs to the Special Issue AIDS Vaccine 2014)
View Full-Text   |   Download PDF [793 KB, 12 May 2015; original version 12 May 2015]   |   Browse Figures
SciFeed

Abstract

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.
Keywords: lentiviral VLP; B-cell proliferation; T-cell proliferation lentiviral VLP; B-cell proliferation; T-cell proliferation
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
EndNote |
RIS
MDPI and ACS Style

Temchura, V.; Kalinin, S.; Nabi, G.; Tippler, B.; Niezold, T.; Überla, K. Divergence of Primary Cognate B- and T-Cell Proliferative Responses to Subcutaneous and Intravenous Immunization with Virus-Like Particles. Viruses 2014, 6, 3334-3347.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert